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Biomedical subjects

C Gagnon

Publications and source records attributed to C Gagnon.

At least 19 recordsLinked to original sources

Purification and characterization of a sperm motility-dynein ATPase inhibitor from boar seminal plasma.

A sperm motility inhibitor from boar seminal plasma was purified. The purification procedure included dialysis against 0.1 M Tris-HCl containing 0.1 mM DTT and chromatographies on SP-Sephadex C-25 and Phenyl-Sepharose CL-4B. With this procedure, the seminal plasma motility inhibitor (SPMI) preparation was highly purified with a 18% recovery of inhibitory activity. The molecular weight of SPMI in native conditions has been estimated at 50,000 by molecular sieving, but 3 polypeptides with molecular weights of 14,000, 16,000 and 18,000 were observed following polyacrylamide gel electrophoresis in denaturing conditions. SPMI is a thermolabile basic protein that is stable between pH 6 and pH 11. The observations that SPMI effects on motility of demembranated spermatozoa are reversed by Mg.ATP and that SPMI inhibited bull dynein ATPase in a concentration-dependent manner suggest that this protein blocks the motility of demembranated spermatozoa by interfering with dynein arm function.

Animals

Formation of reactive oxygen species in spermatozoa of infertile patients.

OBJECTIVE: To determine the incidence of reactive oxygen species formation in semen of a population of patients consulting for infertility. DESIGN: The incidence of reactive oxygen species formation in whole semen and in washed spermatozoa was studied. The values obtained were correlated with semen parameters. The effect of the type of sperm washing on reactive oxygen species formation was also investigated. SETTING: Semen samples from patients consulting for infertility and control subjects were obtained by masturbation after 3 days of sexual abstinence. Reactive oxygen species formation was measured in whole semen, sperm suspension washed by Percoll gradients, or repeated centrifugations. Sperm motility parameters were measured by computer-aided sperm analysis. PATIENTS, PARTICIPANTS: Fertile control men and an unselected population of patients consulting for infertility. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Reactive oxygen species formation by fresh semen specimen or washed spermatozoa was measured in a computer-driven LKB 1251 Luminometer (LKB-Wallac, Turku, Finland). RESULTS: Reactive oxygen species formation was detected in 40% of the semen with spermatozoa from infertile patients, whereas none was found in 6 azoospermic men and 10 control men. The level of reactive oxygen species formation was inversely correlated to the semen volume, the percentage of motile spermatozoa, and sperm linearity both in semen and in Percoll-washed spermatozoa. Washing by repeated centrifugation-resuspension increased 20- to 50-fold sperm reactive oxygen species formation. This enhancement was caused by the centrifugation itself and by the removal of seminal plasma. Both morphologically normal and abnormal spermatozoa produced reactive oxygen species. CONCLUSION: The data suggest that reactive oxygen species formation by spermatozoa may be a significant cause for male infertility.

Centrifugation

Parent-teacher agreement on kindergarteners' behavior problems: a research note.

The present study investigated parameters of agreement as well of disagreement among mothers' and teachers' ratings of the behavior of kindergarten boys and girls. Findings indicated a generally low to moderate level of agreement between these two types of informants. They also suggested that demographic and background characteristics can effect size and direction of level of agreement. Although proportions of children rated as having the listed behavior problems varied in magnitude according to mothers and teachers, the rank order of the proportion of children with those behavior problems was rather similar for both informants. Such similar rankings of prevalence rates may reflect parents' and teachers' agreement on the consistency of children's behavior across the home and school settings.

Anxiety

Behavioural and cognitive characteristics of conduct disordered-hyperactive boys from age 6 to 11: a multiple informant perspective.

Three subgroups of kindergarten boys (stable conduct disordered-hyperactive (SCDH), stable conduct disordered (SCD), stable non-deviant control (SC)) were defined and followed up three, four and five years later in primary school. Using assessments from multiple informants (teachers, mothers, peers, self), the results showed that SCDH boys were more hyperactive (i.e. overactive/inattentive) and displayed a greater diversity of conduct problems in school and home at follow-up compared to the other groups. These results and the fact that during early adolescence SCDH boys tend to develop a worse prognosis than SCD boys suggest that they should be distinguished.

Antisocial Personality Disorder

Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effect of seminal plasma and scavengers.

OBJECTIVE: To investigate whether activated poly-morphonuclear neutrophils (PMN) can affect sperm motility and to assess the capacity of seminal plasma and of scavengers of reactive oxygen species to prevent any loss of motility. DESIGN: Blood PMN were isolated, and their capacity to generate reactive oxygen species was investigated. The effect of activated PMN was tested on the motility of Percoll-washed spermatozoa in the presence and absence of reactive oxygen species scavengers or seminal plasma (whole or fractionated). PARTICIPANTS: Fertile volunteers and patients attending the Infertility Clinic at the Royal Victoria Hospital. RESULTS: The production of reactive oxygen species by activated PMN occurred in the 1st hour after stimulation and was linearly correlated with the concentration of PMN. Percoll-washed spermatozoa had reduced motility in the presence of PMN, and the drop in motility was more severe as the concentration of PMN was increased. Catalase and dimethylsulfoxide reduced the toxic effect of PMN on sperm motility, whereas superoxide dismutase was without effect. Seminal plasma (50%, vol/vol) allowed a highly variable protective effect against the loss of sperm motility that appeared to originate predominantly from the low molecular weight (< 10 kd) fraction but also from the high molecular weight (> 12 kd) fraction of seminal plasma. CONCLUSION: These data suggest that [1] the presence of PMN, even at 0.6 x 10(6) cells/mL, in semen can be hazardous for spermatozoa, [2] H2O2 and .OH are responsible for the loss of motility, and [3H] seminal plasma confers a variable protection due to high and low molecular weight factors.

Free Radical Scavengers

Levodopa-induced dyskinesia: facts and fancy. What does the MPTP monkey model tell us?

Levodopa-induced dyskinesia, one of the most frequent long-term side effects of antiparkinsonian therapy, is often attributed to denervation supersensitivity of dopamine receptors and perhaps more specifically the D-1 receptor. The available evidence based not only on clinico-pathological studies in patients but also on results of experiments performed on methyl-phenyl-tetrahydropyridine (MPTP)-treated monkeys suggests that the mechanisms may be more complex than heretofore believed. Thus it appears that no single receptor is the sole culprit, that some form of denervation supersensitivity is probably involved but not in the form of increased density of dopamine receptors. Moreover, other neurotransmitter systems must be considered such as GABA, excitatory aminoacids and peptides. The MPTP monkey model remains very useful for predicting the potential of new drugs for inducing dyskinesia. Such trials however must be performed in drug-naive animals.

Animals

Regional changes of striatal dopamine receptors following denervation by 6-hydroxydopamine and fetal mesencephalic grafts in the rat.

Young adult female rats received a 6-hydroxydopamine lesion in the left substantia nigra and, 3 weeks later, some of them were grafted with a cell suspension from the ventral mesencephalon of rat embryos (14-15 days old). Six months after transplantation, some grafted rats, following injection of amphetamine, had switched to turning only toward the intact side (type 1), whereas others turned toward the intact side only during the first half of the test (type 2). Levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid were, respectively, 2%, 15% and 35% of the intact side in the denervated striatum of 6-hydroxydopamine rats. Dopamine concentrations were restored to 13% and 10% of the intact side in the grafted striatum of type 1 and type 2 animals, respectively. Levels of homovanillic acid were unchanged following grafts whereas those of dihydroxyphenylacetic acid increased by 209% and 247% in the grafted striatum of type 1 and type 2 animals, respectively. The ratios of dihydroxyphenylacetic acid/dopamine as well as homovanillic acid/dopamine were low in the intact striatum whereas they increased in the denervated striatum with or without graft. The tyrosine hydroxylase immunoreactivity decreased by about 80% in the denervated striatum of 6-hydroxydopamine rats. In type 1 rats, tyrosine hydroxylase immunoreactivity revealed that the graft was localized in the dorsomedial part of the denervated striatum, whereas in type 2 animals, it was also in the medial striatum but it overlapped the dorsal and ventral parts of it equally. D1 as well as D2 dopamine receptors were measured throughout the striatum (9.0-7.6 rostral-caudal coordinates), by autoradiography, using [3H]SCH 23390 (D1 antagonist) and [3H]spiperone (D2 antagonist) binding. Supersensitive D2 receptors were normalized in the dorso- and ventromedial parts of the grafted striatum. D2 receptor density was higher in type 2 than in type 1 rats, more specifically at 8.6-8.2 rostral-caudal coordinates, where the graft was. D1 receptor supersensitivity was modest compared to D2 receptors in the striatum of 6-hydroxydopamine rats and decreased following grafts. DA receptors changes in the striatum, following fetal mesencephalic grafts, may explain the behavioral recovery seen in grafted rats.

Amphetamine

Disruptive boys with stable and unstable high fighting behavior patterns during junior elementary school.

Boys' fighting was assessed at ages six, eight, and nine. The boys (N = 69) had been selected from the 30% most disruptive children in kindergartens from low socioeconomic neighborhoods. Twenty-three percent of these disruptive boys were rated as high fighters on three assessments ("stable high fighters"), and 28% were rated as high fighters on two of the three assessments ("variable high fighters"). Forty-two percent were rated as high fighters only one out of three assessments ("occasional high fighters") and 7% were never rated as high fighters. Only high fighting in two successive years significantly increased the risk of being rated a high fighter in a following year. At age 10, stable high fighters (high fighters at ages 6, 8, 9) were perceived by teachers, peers, mothers, and the boys themselves as more disruptive and more antisocial than occasional high fighters. These results show an impressive self-other agreement in boys who have adopted a physically aggressive life style from an early age. The three groups did not differ on individual family demographic characteristics, but stable high fighters had a higher mean on an index of family socioeconomic disadvantage. Results indicate that the aggression scales which include only a few physical aggression items and many disruptive items (oppositional behavior, rejection, hyperactivity, inattention, etc.) probably aggregate two kinds of disruptive boys, the high-frequency fighters at high risk for stable disruptive, physically aggressive, and antisocial behaviors, and the disruptive low-frequency fighters who are at a lower risk of stable disruptive behavior and at a lower risk of early antisocial behavior.

Aggression

Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [3H]SCH 23390 for D1 receptors and [3H] spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid

Determination of neutrophil concentration in semen by measurement of superoxide radical formation.

OBJECTIVE: To develop an assay that measures the concentration of functional neutrophils in human semen. DESIGN: Human blood neutrophils were first isolated to establish linearity and proportionality for the determination of functional neutrophil concentration. Thereafter blood neutrophils in seminal plasma and neutrophils in semen of patients were measured. SETTING: Blood and human samples were obtained from clinics of the Royal Victoria Hospital. PATIENTS, PARTICIPANTS: Blood from normal men or from patients presenting with chest pain or trauma were used. Semen samples were also obtained from healthy fertile donors or from unselected patients attending the infertility clinic. MAIN OUTCOME MEASURES: Active neutrophil concentration in semen by a colorimetric assay. RESULTS: The assay developed is based on the reduction of nitroblue tetrazolium of pale yellow color to blue formazan by the superoxide anions produced by stimulated neutrophils. The intensity of the derived blue color is proportional to the concentration of active neutrophils. This assay is simple, requires only 10 minutes of preparation time, and detects neutrophil concentrations greater than 0.5 x 10(6) neutrophils/mL of semen, independent of sperm concentration.

Blood Cells

Social and psychological consequences, at 10 years old, of an earlier onset of self-reported delinquency.

In this paper we will answer the following question: what are the consequences of an earlier onset of delinquency on competence several years after onset? Rather than studying the social and psychological predictors of an early onset, we will be interested in the impact of the age of onset of self-reported delinquency on the social and personal adaptation of boys at age 10, social and personal adaptation referring to the broad concepts of competence--"having the requisite or adequate capacity or qualities to function or develop in a particular way" or "sufficiency of means for the necessities and conveniences of life."

Achievement

Can disruptive boys be helped to become competent?

The Montréal Longitudinal Study of Disruptive Boys, an experimental study, was designed to understand boys who were considered disruptive in kindergarten. One part of the study involved assessing effects of a preventive treatment program carried out during the boys' early years in primary school. This paper reports on the outcome of the randomized treatment experiment 3 years after treatments ended. Disruptive boys were randomly allocated to a treated group and two nontreated groups. Treatment consisted of parent training and training of boys for social skills, fantasy play and television viewing. Results suggest that the treatment program had some positive effects. Some of the improvements were not evident immediately after treatment ended.

Achievement

Quantitative assessment of the serum-induced stimulation of human sperm motility.

In previous studies, sperm populations with high motility and fertilizing potential have been isolated using Percoll gradients and/or addition of serum or caffeine, but no objective measurements of the motility parameters affected have been presented. In addition, the types of sperm populations and the incidence of positive or negative responses to these treatments have never been documented. In this paper, the proportion of samples responding positively or negatively to these treatments and the type of motility stimulation observed was measured using the CellSoft computer-assisted digital image analysis system. Semen, obtained from the Infertility Clinic, was washed on discontinuous Percoll gradients. Sperm motility parameters were measured in the original semen and after washing through a Percoll gradient in the presence or absence of serum or caffeine. Percoll washing permitted a good recovery of essentially pure sperm. The Percoll treatment had little effect on the percentage of motile sperm but caused a decrease in the linearity-related parameters. A high proportion of the washed sperm samples supplemented with serum showed an increase in at least one of the motility parameters when compared to sperm populations in the original semen (68% of cases) or after Percoll washing (96% of cases). These effects were maintained for several hours. The stimulation of motility was concentration-dependent, with an optimum around 25-30% serum. Caffeine (4 mM) increased linear velocity but lowered linearity. In contrast to caffeine, which stimulated sperm motility for less than 1 h, the effects of human serum lasted for more than 16 h.

Biological Factors

Origin of the human seminal plasma motility inhibitor within the reproductive tract.

The origin of a human seminal-plasma sperm-motility inhibitor was investigated. Seminal vesicle and prostatic fluids, testes, epididymides, prostate and seminal vesicles were collected from young cadavers. The motility inhibitor, as measured by its capacity to block the motility of demembranated-reactivated sperm was present in significant amounts only in seminal vesicle fluid. The level of biological activity in this fluid was 13.6-fold higher than in seminal plasma. However, the concentration of motility inhibitor, as measured by ELISA, using an antibody generated against the motility inhibitor purified from human seminal plasma, was only 1.54-fold higher than in seminal plasma. The data suggest that the seminal plasma motility inhibitor originates from seminal vesicle fluid and that it is processed into a nine-fold less biologically active form when seminal vesicle fluid is mixed with other accessory gland secretions at ejaculation.

Animals

[Apropos of a case of thermal epiglottitis].

A case of thermal epiglottitis in a 15 month-old infant after swallowing a scalding hot liquid is presented. Intubation was maintained during 3 days. The evolution was simple without corticosteroid therapy.

Epiglottitis

Presence of a new microtubule cold-stabilizing factor in bull sperm dynein preparations.

Brain tubulin polymerized with dynein isolated from bull spermatozoa forms cold-stable microtubules, in contrast with microtubules made of brain tubulin polymerized by brain microtubule-associated proteins (MAPs). The level of cold-stable microtubules depends on the concentration of dynein used. Addition of dynein to cold-unstable microtubules renders these microtubules stable to cold. Although ATP and a non-hydrolysable ATP analogue increase the formation of microtubules made of tubulin and dynein, these nucleotides have no effect on dynein cold-stabilizing properties. The data suggests that a new factor, not involving the dynein ATPase active site and present in bull sperm dynein preparations, confers cold-stability to microtubules.

Adenosine Triphosphate

Effect of chronic treatment of MPTP monkeys with dopamine D-1 and/or D-2 receptor agonists.

A severe parkinsonian syndrome developed in four monkeys after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One monkeys subsequently remained untreated, and each of the three others were treated daily for at least one month with Sinemet, bromocriptine or SKF 38393. An intact control monkey (not MPTP-treated) was also included in the experiment. Sinemet and bromocriptine relieved the parkinsonian symptoms, whereas SKF 38393 was ineffective. The animal treated with Sinemet developed dyskinesia while those treated with bromocriptine or SKF 38393 did not. MPTP decreased dopamine levels by more than 99% in the striatum of all monkeys. Striatal D-1 and D-2 dopamine receptor densities as evaluated by autoradiography of [3H]SCH 23390 and [3H]spiperone binding were increased by 66 and 51%, respectively, after MPTP. Sinemet, bromocriptine or SKF 38393 treatment decreased D-2 receptor density, respectively, by 17, 84 and 35% and D-1 receptor density by 28, 33 and 6% vs. that in MPTP-treated animals. Our results suggest that dopamine receptor changes could be implicated in the loss of efficacy and in the side-effects of these treatments.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine