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Biomedical subjects

M Fournier

Publications and source records attributed to M Fournier.

At least 235 records · Page 13Linked to original sources

Virus-pesticide interactions with murine cellular immunity after sublethal exposure to dieldrin and aminocarb.

Interaction of two potential immunosuppressive factors, sublethal pesticide exposure and viral inhibition of lymphocyte mitogenesis, was examined in mixed lymphocyte reaction (MLR). Inbred (C57Bl/6 x A/J)F mice, semisusceptible to mouse hepatitis virus 3 (MHV3) infection were exposed to selected pesticides and subsequently infected with the MHV3 virus. The mortality of animals was examined as a function of pesticide exposure. Two pesticides were selected for further studies: the organochlorine pesticide dieldrin, which increased the cumulative mortality of animals, and the carbamate pesticide aminocarb, which did not affect the virus-induced cumulative mortality of animals. Spleen lymphocytes from dieldrin- and aminocarb-exposed C57Bl/6 mice (susceptible to MHV3 infection) were used as responder cells in one-way MLR. A marked immunosuppression of the MLR proliferative response was observed in the dieldrin group, whereas sublethal exposure to aminocarb did not affect the in vitro MLR response. The MLR cultures were subsequently infected in vitro with the MHV3 virus, which resulted in a time-dependent and virus dose-dependent inhibition of lymphocyte proliferation. However, no synergism was observed with the addition of either the MHV3 virus-induced inhibition of in vitro MLR lymphoproliferative response or dieldrin-related immunosuppression, since in vitro MHV3 infection of cells from dieldrin-exposed mice did not aggravate the dieldrin-related immunosuppression. In addition, no "hidden" aminocarb-related damage of the lymphoproliferative response was noted, as the kinetics of the virus-induced inhibition in the aminocarb group were analogous to the control. In conclusion, dieldrin-induced immunosuppression of the cellular immune response, rather than MHV3 virus-induced inhibition of lymphoproliferative activity itself, was the primary factor potentially responsible for the impaired cellular response. Furthermore, the data support the observation that cell-mediated immunity can be a potential target for the adverse effects of pesticide exposure.

Animals↗

Somatotopy in the segmental innervation of the cat diaphragm.

A somatotopic organization in the segmental innervation of the cat diaphragm (DIA) was determined using evoked electromyographic responses and glycogen depletion of stimulated type II muscle fibers. With the use of the glycogen depletion method, the specific location and proportion of muscle fibers innervated by the fifth (C5) or sixth (C6) cervical ventral roots were determined for different regions of the DIA. The sternal and ventral portions of the costal and crural DIA regions were innervated primarily by C5. The dorsal portions of both the costal and crural regions were innervated primarily by C6. Thus the somatotopic organization in the segmental innervation of the DIA was not correlated with the anatomic division of the sternal, costal, and crural regions. Instead, the somatotopic projections of cervical ventral roots were organized in the ventrodorsal axis of each DIA region. This topographical pattern resulted in an extensive overlap of the DIA territories innervated by C5 and C6. Within a region, the fibers innervated by a specific ventral root were not randomly distributed but often followed fascicle divisions. This frequently resulted in a wide range in the proportion of fibers innervated by a ventral root even within a specific region.

Animals↗

Mechanical properties of muscle units in the cat diaphragm.

1. Muscle units in the right sternocostal region of the cat diaphragm (DIA) were isolated in situ by dissecting filaments of the C5 ventral root. Isometric contractile and fatigue properties of DIA units were then measured. Contractile properties included: twitch contraction time (CT), peak twitch tension (Pt), maximum tetanic tension (P0), and the frequency dependence of tension production. Muscle-unit fatigue resistance was estimated using a 2-min fatigue test. 2. DIA muscle units were classified as fast (F) or slow (S) based on the presence or absence of sag in their unfused tetanic force responses. Muscle-unit fatigue indices (FI) were used to further classify DIA units as slow-twitch fatigue-resistant (S), fast-twitch fatigue-resistant (FR) fast-twitch fatigue-intermediate (FInt), or fast-twitch fatigable (FF) types. 3. Based on a total of 47 completely characterized DIA muscle units, 21% were classified as S, 4% as FR, 28% as FInt, and 47% as FF. In contrast to the distribution of unit types in other mixed appendicular muscles, the DIA was composed of a very low proportion of FR units and a relatively high proportion of FInt units. An interval of FIs between 0.50 and 0.75 separated units into fatigue-resistant and fatigable groups. The distribution of FIs for FF and most FInt units was continuous, indicating that they formed a single fatigable group. Relatively few FF units in the DIA had FIs less than 0.10. 4. A wide range of contractile properties was observed for DIA muscle units. Type S units had longer CTs and lower Pt and P0 values than type F units. The mean Pt and P0 of FF and FInt units were comparable, whereas the mean Pt and P0 of the two FR units were lower. Type S units produced a greater proportion of their P0 at lower frequencies of activation than type F units. The lower P0S produced by type F units in the DIA indicated that they were smaller than similar units in appendicular muscles. It was concluded that in meeting most normal ventilatory requirements, adequate force could be generated by the recruitment of only type S and FR units. The recruitment of the more fatigable FF and FInt units may occur only during more forceful respiratory and nonrespiratory behaviors of the DIA.

Animals↗

Sequential bronchoalveolar lavage in experimental extrinsic allergic alveolitis. The influence of cigarette smoking.

We studied the alterations induced by acute experimental extrinsic allergic alveolitis (EAA) on bronchoalveolar cell population in smoking and nonsmoking guinea pigs. Sixty-two animals divided into 3 groups were studied: Group 1 (17 animals), controls; Group 2 (21 animals), extrinsic alveolitis; Group 3 (24 animals), cigarette smoking and alveolitis. Bronchoalveolar lavages (BAL) were performed on Days 1, 19, and 44 for all animals. Group 3 animals had a fourth lavage before starting cigarette smoking, that is, 28 days before the beginning of the antigen injections. The other lavages were as for the other groups. BAL results on Day 1 were similar for each group. Cigarette smoking per se did not modify BAL in Group 3. EAA induction resulted in a large increase in all BAL cells, especially neutrophils of recovered fluid, which increased from 38 x 10(3) to 1,474 x 10(3) ml-1 (p less than 0.01) in Group 2 and from 58 x 10(3) to 740 x 10(3) in Group 3 (p less than 0.01). After maintenance, BAL neutrophils.ml-1 decreased to 444 x 10(3) in Group 2 (p less than 0.01), but stayed the same in Group 3: 973 x 10(3). After EAA induction, BAL neutrophils.ml-1 were higher in Group 2 than in Group 3 (p = 0.039); however, Group 2 had less neutrophils.ml-1 than Group 3 (p = 0.035) after EAA maintenance. We conclude that EAA results in a neutrophilic alveolitis and which can be evaluated by sequential BAL, and that cigarette smoking decreases the initial neutrophilic response and retards the eventual recovery during maintenance injections.

Acute Disease↗

N-ethylmaleimide differentially affects adenosine and thymidine uptake by rat thymocytes.

The involvement of membrane sulfhydryl groups in the uptake of adenosine and thymidine was examined in rat thymocytes pretreated with 6,6'-dithiodinicotinic acid (CPDS) and N-ethylmaleimide (NEM). CPDS, which is known to react uniquely with external membrane sulfhydryls, under short incubation conditions, did not significantly affect the uptake of adenosine and thymidine. Formation of cAMP in nonstimulated and adenosine-stimulated cells was also unaltered by CPDS. However, inhibition of adenosine uptake by competitive inhibitor, dipyridamole, was significantly stronger when the cells were pretreated with CPDS. Preincubation of cells with NEM showed differential sensitivity of adenosine and thymidine uptake, depending on concentration of this sulfhydryl alkylating agent. The results suggest the involvement of NEM-accessible sulfhydryls in membrane transport of adenosine and thymidine. Dual effect of NEM on nucleoside transport may be related to the complexity of nucleoside carrier(s) or to the existence of different nucleoside carriers within thymocyte membranes. On the other hand, the easily accessible, external membrane -SH groups which can be blocked with CPDS, are not essential in thymocyte nucleoside transport but they appear to be situated at a site which interacts with the membrane transport system of nucleoside.

Adenosine↗

[Results of surgical treatment of alphabetical syndromes in esotropia. Apropos of 98 cases].

The authors report the results of 98 cases of esotropia treated by global surgery. They treated 72 "V" syndromes, 22 "A" syndromes and 4 cases without vertical incommitance but presenting visible hyperactivities of the oblique muscles. The alphabetical variations have been treated by weakening of the oblique muscles and sometimes have been treated by weakening of the oblique muscles and sometimes of the vertical recti which are part of the same torsional couple (inferior oblique - inferior rectus in the "V" syndrome, superior oblique - superior rectus in the "A" syndrome). Post-operative improvement has been obtained in 76% of the cases for the "V" syndrome and in 63% of the cases for the "A" syndrome. The surgery of the oblique muscle must be done according to the importance of the incommitance. The arc-technique permits these adjustments. Some pronounced "X" syndromes appear in the post-operative period. All anomalies found during motility examination should be surgically corrected.

Child↗

Binding stoichiometry of tRNATrp and tryptophanyl-tRNA synthetase from bovine pancreas under pH conditions of maximum activity. Analysis by ultracentrifugation, fluorescence quenching and chemical modification.

The binding stoichiometry of tRNATrp and tryptophanyl-tRNA synthetase (EC 6.1.1.2) from beef is examined by three approaches, under pH conditions of maximum activity (pH 8.0). (1) Analytical ultracentrifugation evidences the binding of a single mol of tRNATrp in a 2.5-10 microM concentration range. (2) tRNATrp quenches the fluorescence of the enzyme. The dependence of this fluorescence quenching on the tRNATrp concentration (0.1-4 microM) reflects also the binding of 1 mol of tRNA per mol of enzyme, with a Kd value of 0.19 +/- 0.02 microM. (3) tRNATrp protects the enzyme against derivatization by oxidized ATP. Out of the two fast-reacting lysine residues of the native enzyme, only one is prevented from reacting by tRNATrp in the 0.5-110 microM concentration range. This protection can be significantly analyzed only by assuming a one-to-one complex between the enzyme and tRNA. These results, obtained at pH 8.0 and 25 degrees C, are in contrast with the stoichiometry of 2 mol of tRNA to 1 mol of enzyme, previously observed at pH 6.0 and 4 degrees C.

Amino Acyl-tRNA Synthetases↗

Reaction of tryptophanyl-tRNA synthetase from beef pancreas with periodate-oxidized ATP.

Tryptophanyl-tRNA synthetase from beef pancreas reacts with periodate-oxidized ATP according to biphasic kinetics. A rapid phase involves two groups of the protein, presumably lysine side-chains. The slow phase corresponds to the reaction of a larger number of groups. The time-course of the partial losses of the ATP-PPi isotopic exchange and of the aminoacylation activities of the enzyme follow the labelling of the two fast-reacting groups. However, the ability of the enzyme to form a bis(tryptophanyladenylate)-enzyme complex is not lost after reaction of these two groups with the reagent. The affinity for ATP is also unaffected by this initial labelling of the protein, as seen from the Km values of this substrate in the ATP-PPi isotopic exchange reaction. These data suggest that, in this fast initial reaction, oxidized ATP reacts neither with specific ATP-binding groups of the enzyme nor with any major catalytic residue of the tryptophan-activation site. In contrast with this first step, the further slow labelling of lysine residues leads to a disappearance of the aminoacylation ability of the enzyme, while it does not further affect the ATP-PPi exchange activity. The behaviour of beef tryptophanyl-tRNA synthetase during derivatization with oxidized ATP is therefore at variance with that which has been described for the homologous E. coli enzyme.

Adenosine Triphosphate↗

Immunosuppression in mice after inhalation of cadmium aerosol.

Aerosol cadmium (CdCl2) exposure of female C57Bl/6 mice was performed to assess the in vivo effects of cadmium on the cellular and humoral immune responses of splenic lymphocytes. Primary cellular and humoral responses of lymphocytes were examined at 5-18 days after a single, 60 min exposure to 0.88 mg Cd/m3 (MMAD = 0.7 +/- 0.3 micron, sigma g = 3.43). Significant decrease of in vitro lymphoproliferative response to allogeneic antigens, LPS and PHA antigens, and inhibition of the primary IgM response to sheep erythrocytes were correlated with a marked decrease in spleen cell viability at 5-8 days after aerosol cadmium exposure. This type of cadmium-induced immunosuppression, which correlated with the direct cytotoxicity of effector cells, appeared to be different from the chronic, oral cadmium-induced suppression of the primary IgM response, in which acute cytotoxicity of the spleen cell population was not observed.

Administration, Inhalation↗

Suppression of humoral immunity in inbred mice by dieldrin.

The effect of single, sublethal i.p. injection of dieldrin on the primary antibody response to thymodependent (sheep red blood cells, SRBC) and T-cell-independent (lipopolysaccharide, LPS) antigens were investigated in inbred C57Bl/6 mice. Time-course studies showed significant suppression of the anti-SRBC IgM and anti-LPS IgM response at 7-24 days and at 4-14 days, respectively, after exposure to 0.6 LD50 of dieldrin. The anti-SRBC IgG response was also suppressed by dieldrin exposure, however, maximal suppressory effect was found at 48 days after the pesticide exposure. Similar patterns of the dieldrin-induced suppression of the primary IgM response to the thymodependent and T-cell-independent antigens, in addition to the overall control of cytotoxicity of lymphoid cell populations, suggest rather dysfunction of cellular cooperation during the inductory phase of the immune humoral response.

Animals↗

Suppression of MHV3 virus-activated macrophages by dieldrin.

Dieldrin (36 mg/kg body weight) administered intraperitoneally prolonged recovery from infection with mouse hepatitis virus 3 (MHV3) in the genetically-resistant A/J strain, affected the humoral anti-MHV3 IgG immune response, and inhibited the intrinsic antiviral activity of peritoneal macrophages upon in vitro rechallenge with the virus. Infection of untreated A/J animals and vehicle controls with MHV3 resulted in marked and reproducible activation of peritoneal macrophages, observed in vitro as resistance to MHV3-cytopathic effects 48 hr after rechallenge with the virus, whereas exposure to dieldrin resulted in apparent loss of the intrinsic capacity of cells to restrict replication of MHV3 and to protect them from cytolysis. In addition, in vitro treatment of MHV3 virus-activated macrophages with dieldrin, mitomycin C and X-irradiation, inhibited the intrinsic capacity of cells to restrict MHV3 replication. This mechanism of cellular restriction of the virus by MHV3-activated macrophages from the resistant A/J strain appeared to be one of the sensitive targets for the suppressive action of dieldrin on host resistance, as no major changes in macrophage cellular parameters were observed in in vitro studies of cell viability, adherence to plastic, and superoxide anion generation; the increased cell yield in the peritoneal exudates during MHV3 virus infection was not affected by dieldrin exposure; and the attachment and uptake of [3H]MHV3 by virus-activated macrophages was shown to be unchanged by dieldrin exposure.

Animals↗

Tryptophanyl-tRNA synthetase is a major soluble protein species in bovine pancreas.

Besides their central role in protein synthesis, aminoacyl-tRNA synthetases have been found or thought to be involved in other processes. We present here a study showing that tryptophanyl-tRNA synthetase has a surprising tissular distribution. Indeed, immunochemical determinations showed that in several bovine organs such as liver, kidney and heart, tryptophanyl-tRNA synthetase constitutes, as expected, about 0.02% of soluble proteins. In spleen, brain cortex, stomach, cerebellum or duodenum, this amount is about 10-times higher, and in pancreas it is 100-fold. There is no correlation between these amounts and the RNA content of the organs. Moreover, the concentration of another aminoacyl-tRNA synthetase (methionyl-tRNA synthetase) is higher in liver than in pancreas, while the amount of tRNATrp is not higher in pancreas than in liver as compared to other tRNAs. Among several interpretations, it is possible that tryptophanyl-tRNA synthetase is involved in a function other than tRNA aminoacylation. This unknown function would be specific to the differentiated organs, since fetal cerebellum and fetal pancreas contain the same amount of tryptophanyl-tRNA synthetase as adult liver.

Amino Acyl-tRNA Synthetases↗

Correlation between the morphology and the lipid and protein compositions in the peripheral nervous system of individual 8-day-old normal and trembler mice.

The hereditary, hypertrophic interstitial neuropathy which afflicts the trembler mouse manifests itself about two weeks after birth. Consequently, the identification of these mutant mice was not possible before this age, except when double mutants were available. We show that the trembler mice can be easily distinguished from their normal littermates before the clinical symptoms appear by using an HPTLC/densitometry technique that allows the simple and rapid analysis of the polar lipids extracted from one sciatic nerve. The results presented in this paper demonstrate important differences between the polar lipid compositions of sciatic nerves from 8-day-old normal and trembler littermates, whose phenotypes were confirmed by the morphological analysis of the contralateral sciatic nerves. The small amount of material that is needed for this identification makes it possible to use the remaining nerve material for other studies. Furthermore, important differences between the sciatic nerve protein compositions of normal and trembler mice, identified according to their polar lipid composition, were also observed and these differences can, therefore, also be employed for the identification of the mutants before the manifestation of the clinical symptoms of the trembler neuropathy.

Animals↗

Effect of nutritional deprivation on diaphragm contractility and muscle fiber size.

The influence of nutritional deprivation on the contractile and fatigue properties of the diaphragm was studied in adult rats. Food access was restricted to one-third of normal daily intake until the body weight of nutritionally deprived (ND) animals was approximately 50% of controls (CTL). Isometric contractile properties were studied in an in vitro nerve muscle strip preparation. Both twitch (Pt) and tetanic (Po) tensions of diaphragms from the ND animals were markedly reduced compared with CTL; however, Pt/Po was higher for the ND group. The shape of the force-frequency curve (normalized to Po) was generally similar between the two groups, except at 5 and 10 pulses/s stimulation, where greater relative tensions were produced in diaphragms from the ND animals. Diaphragm fatigue was induced by repetitive stimulation at either 20 or 100 pulses/s. Endurance time (defined as the time required for tension to fall to 50% of initial) of diaphragms from ND animals was prolonged at both 20 and 100 pulses/s. Immediately after induction of fatigue, force-frequency curves for both ND and CTL diaphragms were shifted to the right. However, this rightward shift was attenuated in the ND group compared with CTL. Nutritional deprivation had no effect on the proportions of different fiber types within the diaphragm but did result in a significant decrease in the cross-sectional area of both fast-and slow-twitch fibers. This decrease in cross-sectional area was significantly greater for fast-twitch fibers. We conclude that these changes in diaphragm contractile and fatigue properties occur as a result of the influence of malnutrition on muscle fiber cross-sectional area.

Animals↗

Soleus motor units in chronic spinal transected cats: physiological and morphological alterations.

Intracellular recording and stimulation were used to study electrical properties of soleus motoneurons and isometric contractile properties of their muscle units. In addition, some muscle units were depleted of glycogen for purposes of studying their morphology. These data were compared for two experimental groups of barbiturate-anesthetized adult cats: those with spinal cords intact (normal) and others with spinal cords transected (ST) 4 mo before study. The greatest change in soleus motoneurons after ST was a decrease in afterhyperpolarization (AHP) duration. Axonal conduction velocity (CV) increased slightly, yet consistently. These data confirm previous findings. The voltage threshold of motoneurons, estimated from the product of rheobase current and input resistance, increased from the normal value of 7.5 mV to 10.1. This resulted from a significant increase in rheobase current after ST, because input resistance was not altered significantly. These data suggest that motoneuron excitability decreased after ST and therefore cannot account for hyperreflexia in chronic ST cats. Measurement of soleus muscle unit isometric contractile properties generally confirmed earlier reports of decreases in twitch time course [both contraction time (CT) and half-relaxation time] and in twitch (Ptw) and maximum tetanic (Pmax) tensions after chronic ST. The ratio Ptw/Pmax increased as a result of a greater decline in tetanic than in twitch tension. No significant change was observed in the fatigue index. Direct measures of muscle unit morphology showed that the specific tension for three ST units fell below the range of four normal units. This was expected given that the innervation ratio was not altered and that the decrease in muscle fiber area after ST was proportionately smaller than the decrease in Pmax. Two lines of evidence showed that motoneuron and muscle unit properties were coordinated before and after ST. First, the normal correlation between AHP duration and CT was nearly as strong after as before ST, and the slope of this relation was not significantly different for normal and ST groups. Second, multivariate statistics (canonical analysis) showed that a combination of all motoneuron electrical properties listed above was strongly correlated with a combination of muscle unit twitch time, Pmax, and Ptw/Pmax for normal and ST groups. In contrast with the conclusions of Gallego et al., we suggest from these data that SOL motor-unit properties are coordinated after ST.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗