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Biomedical subjects

L Gagnon

Publications and source records attributed to L Gagnon.

72 records · Page 4Linked to original sources

Augmentation of human natural cytotoxic cell activity by leukotriene B4 mediated by enhanced effector-target cell binding and increased lytic efficiency.

The addition of leukotriene B4 (LTB4) to cytotoxicity assays measuring natural killer (NK) or natural cytotoxic (NC) cell activities resulted in significantly augmented killing of K562 or herpes simplex virus (HSV)-infected target cells, respectively. Since the mechanism of cytotoxicity implies several steps, including the binding of effectors to targets which is Mg2+-dependent and the programming of lysis of the target which is Ca2+-dependent, we undertook to define the step(s) at which LTB4 acted in augmenting cytotoxicity. Our results showed that LTB4 significantly increased the percentage of effector-target conjugates when K562- or HSV-infected targets were incubated with lymphocytes. Maximal binding occurred at a concentration of LTB4 of 1 X 10(-10) M. Preincubation of lymphocytes and not target cells with LTB4 was sufficient to observe the increased binding. PBML binding to and killing of the NK-resistant target clone I, derived from K562, was not enhanced by LTB4. In the absence of Ca2+, cytotoxicity was impaired and LTB4 could not restore it. Use of a single cell lytic assay demonstrated augmented efficiency of lysis of both K562 and HSV-infected targets in the presence of LTB4. These findings suggest that LTB4 may augment natural cytotoxicity by enhancing target cell recognition by cytotoxic effector cells and subsequently by augmenting their lytic efficiency.

Antibodies, Monoclonal↗

Evidence for the involvement of the thromboxane synthase pathway in human natural cytotoxic cell activity.

We and other investigators have recently shown that inhibitors of lipoxygenase reversibly inhibit natural cytotoxic (NC) or natural killer (NK) cell activity, whereas some inhibitors of cyclooxygenase enhance these functions. In addition, exogenous LTB4 augments NC and NK activity, whereas PGE2 depresses it. In the present studies, we sought to investigate the possible role of the TxA2 synthase pathway in NC function. Inhibition of this pathway by OKY-1581 or dazoxiben significantly inhibited NC activity against HSV-infected cells as well as NK function against K562 target cells. The inhibition was dose dependent, reversible, and not due to direct toxicity. NC activity was also significantly inhibited by the addition of PGE2 or PGI2 to the 4-hr assay, whereas addition of 6-keto-PGF1 alpha had no effect. Addition of PGH2, which could be converted to TxA2 or other PG, had no significant effect, but concomitant use of OKY-1581 produced a greater inhibition of NC function than by using OKY-1581 alone. U44069, a TxA2 analog, was inhibitory by itself and could not alter the inhibition caused by OKY-1581 or dazoxiben. In contrast, the TxA2 receptor blocker 13-APA significantly enhanced NC activity and even reversed the inhibitory effect of U44069 at equimolar (10(-7)M) concentrations. Taken together, these data suggest that most of the inhibitory effect of the TxA2 synthase inhibitors on NC and NK cell function derives from their ability to reorient cyclic endoperoxide metabolism toward more inhibitory compounds. In addition, TxA2 itself could exert a negative feedback on NC function through its receptor, as evidenced by the use of a TxA2 analog and a TxA2 blocker.

Cytotoxicity Tests, Immunologic↗

Leukotriene B4 augments human natural cytotoxic cell activity.

We have recently shown that leukotriene B4 (LTB4) activates T lymphocytes to become suppressor cells. We now report that LTB4 also augments human natural cytotoxic cell activity against target cells infected with herpes simplex virus. This activity is partially inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid and the thromboxane synthetase inhibitor OKY-1581, but is augmented by indomethacin. We suggest that LTB4 may play a role in early host defense responses during inflammatory and infectious disease processes.

Humans↗

Periods of activity and quiescence in the premature EEG.

Periods of inactivity or quiescence (Q) alternating with periods of activity (A) were measured in 184 prematures, compared to 277 full-term infants. Q periods appeared in all prematures up to 32 wks conceptional age (CA), and then the incidence curve linearly fell to near-zero (8%) at term. The A periods increased from 2% of the recording time at 24 wks to 80% at 34 wks. Other measures of central tendency showed an increase in A or A + Q with age until 34 wks and a decrease in Q until 29 wks. Except when using percentile and mean values which show great variability, a pair of A and Q values are usually independent of each other. On the other hand, high A values often precede or follow the highest A's and high Q's similarly are often grouped together. Q and A periods were studied with regard to clinical outcome. Patients who later expired in the neonatal period showed no increase in A with age, in contrast to living patients showing a significant increase with age. The longest durations of Q (after A) and shortest durations of A (after Q) were seen in patients who later expired followed by living patients with major sequelae, and then by normals or those with only minor sequelae. The clinical categories of major vs. minor sequelae were also different with regard to the longest A period measured. For prognostic purposes, curves (based on % of recording time with A) are presented that allow a successful prediction of survival or death and also predict generally a good or poor prognosis. Neurophysiological, neuroanatomical and neuropathological implications are discussed.

Electroencephalography↗

The use of the electroencephalogram in the confirmation of seizures in premature and neonatal infants.

This study, involving 236 patients (pts) of 24-48 wks conceptional age, was designed to determine how well the interictal EEG could confirm a seizure (SZ) disorder in prematures and neonates. "Burnt-out" (B) sharp waves were frequently (80%) associated with SZ, as were positive (P) sharp waves (75%). The latter, more often on the temporal than central areas, were found in 1/3 of pts with intraventricular hemorrhage (IVH) and nearly 1/3 with P sharp waves had IVH. Other focal (negative) discharges were found in the majority of the pts and their frequency of occurrence was investigated as the major variable to confirm a SZ disorder. Along with B and P sharp waves, the other focal discharges at the average frequency of 1/min confirmed too few of the SZ pts (36%) and at 0.3/min included too many (34%) of the NON-SZ pts. Using the criterion of 0.5/min, only 18% of the NON-SZ pts were included as false positives, but over half of SZ pts (52%) were then identified and 73% with these discharges did have SZ. Thus, this study has emphasized that correlation and confirmation of a SZ disorder likely depends on quantified, statistical considerations, especially the frequency of occurrence of an interictal discharge.

Age Factors↗

[Prospective study of arterial pressure during pregnancy. Prediction of hypertensive complications].

A prospective study of measure of blood pressure was conducted in 366 pregnant women at each antenatal visit, using an automatic random-zéro sphygmomanometer. In fourteen patients, among 244 primigravidae, who developed preeclampsia, systolic and diastolic arterial blood pressures were already significantly elevated by 13-16 weeks of pregnancy. This difference was sustained throughout until delivery. In addition, the systolic and diastolic arterial blood pressure, in those women destined to develop preeclampsia, did not show a dip between 13-20 weeks as in the normotensive group. There was no difference in arterial blood pressure during pregnancy between primigravidae and multigravidae who remained normotensive.

Blood Pressure↗

The importance of phase of stimulus and the reference recording electrode in brain stem auditory evoked potentials.

In normal subjects the phase of the stimulus and the reference electrode of the brain stem auditory evoked potential (BAEP) were investigated. Compared to condensation (C), rarefaction (R) clicks produced longer latencies, especially for peaks IN, IIIN and IV and lower amplitudes, mainly for IIN. The amplitude of the initial phase of R clicks was lower in the acoustical wave form (with piezoelectric phones) than the succeeding higher amplitude C phase, but damping characteristics varied with recording conditions. In comparing Ipsi vs. Contra ear reference the Ipsi showed a shorter latency for II and IIN, a longer latency for III, IIIN and IV and a higher amplitude, except for II. The relative contribution of the central vertex (Cz) and of each ear to the standard Cz-ear linkage was determined by referring each to an indifferent electrode. The activity at the Ipsi ear was out of phase with Cz up to peak IV, especially I, IN and III (but not II) with a resulting high amplitude in the Cz-ear linkage; in-phase relationships were noted between Cz and the Contra ear resulting in a relatively low amplitude in the Cz-Contra ear linkage. Discussion of the latter points included the complex, but significant changes of the amplitude and latency of Cz activity by an ear reference.

Acoustic Stimulation↗

Laterality effects in processing tonal and atonal melodies with affective and nonaffective task instructions.

Right-handed university subjects were presented with monaural melodies that either conformed to the rules of the Western tonal system (tonal melodies) or that systematically deviated from it (atonal melodies) while containing similar contours and pitch skips. Subjects were tested under two different task instructions. One group was requested to judge whether each melody sounded correct or not (the nonaffective task); the other group had to judge whether each melody sounded pleasant or not (the affective task). The nonaffective task was found to elicit essentially no ear difference. In contrast, the affective instruction induced opposite and reliable laterality effects, depending on the valence of the response. The pleasant responses were indicative of a left hemisphere predominance and the unpleasant responses of a right hemisphere predominance. The results are consistent with the claim that the left hemisphere is biased toward positive emotions and the right to negative emotions. Moreover, the results suggest that affective appreciation of melodies is dissociable from their nonaffective judgment.

Adult↗

Secondary impairments after spinal cord injury: a population-based study.

OBJECTIVE: To determine the prevalence of secondary impairments among individuals with long-standing spinal cord injury in Quebec and the potential relationships between these impairments and several variables. DESIGN: A review of 2,200 medical files was conducted to determine the target population; 976 patients were selected randomly and mailed questionnaires. The results were based on 482 individuals with spinal cord injury who returned the completed questionnaire. The questionnaire included 14 subsections, such as sociodemographic, medical, psychosocial, and environmental information. The medical section, including the type and level of lesion and the presence of secondary impairments, was analyzed. RESULTS: Urinary tract infection, spasticity, and hypotension were the most frequently reported secondary impairments, regardless of the severity of injury. Relationships between the prevalence of secondary impairments and the duration of injury, as well as perceived health status, were observed. CONCLUSIONS: This is the first study to describe secondary impairments after long-standing spinal cord injury in Quebec. Patients with spinal cord injury still present a high prevalence of secondary impairments many years after their rehabilitation, despite preventive education or medical follow-up visits. Further studies are required to determine the specific impact that these impairments have on the patients' social role and their quality-of-life.

Adult↗

[Nutritional recommendations and risk of death from all causes].

This study evaluated the relationship between meeting the Nutrition Recommendations and mortality from all causes in a cohort of 1,623 men from the Quebec City area followed from 1985 to 1991. The usual dietary intake was assessed by a self-administered semi-quantitative food frequency questionnaire. Most participants did not meet the Nutrition Recommendations. During the follow-up 69 men died. The mortality was significantly lower among those who did not meet the recommendations for total fat (RR = 0.45, CI: 0.25-0.81) or for carbohydrates (RR = 0.49, CI: 0.26-0.92). This unexpected result could be attributable to an excessive alcohol intake or to dietary changes in the direction of the Nutrition Recommendations, made prior to the dietary assessment often because of illness. It would be interesting to continue the follow-up of this cohort to evaluate the long-term effect of a diet meeting the Nutrition Recommendations on mortality from all causes.

Aged↗