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Biomedical subjects

J Leblanc

Publications and source records attributed to J Leblanc.

At least 19 recordsLinked to original sources

Effects of fasting and food restriction on sympathetic activity in brown adipose tissue in mice.

The activity of the sympathetic nervous system in mice that were either fed ad libitum, food restricted or fasted was estimated by measuring the accumulation of dopamine following the inhibition of dopamine beta-hydroxylase activity. Mice in each group were injected with the dopamine beta-hydroxylase inhibitor 1-cyclohexyl-2-mercaptoimidazole and were exposed to either 30 degrees C (warm) or 4 degrees C (cold). Mice were killed 1 h after the injection. Both heart and brown adipose tissue were then quickly removed and homogenized in ice-cold perchloric acid. Dopamine and noradrenaline were determined using high performance liquid chromatography. Regardless of whether mice were warm or cold exposed, both content and concentration of brown adipose tissue and dopamine were predictably higher in 1-cyclohexyl-2-mercaptoimidazole-injected mice than in non-injected animals. In mice fed ad libitum, post-injection content and concentration of dopamine in both brown adipose tissue and heart were higher in cold-exposed mice than in warm-exposed animals. In food-restricted and fasted mice, post-injection concentrations of dopamine in brown adipose tissue were higher in cold-exposed mice than in warm-exposed animals. In food-restricted and fasted mice there was no difference between warm- and cold-exposed animals with respect to post-injection contents and concentrations of dopamine in heart tissue. In fasted mice there was no difference between warm- and cold-exposed animals in post-injection content of dopamine in brown adipose tissue. This study provides further evidence that fasting, in contrast to food restriction, may blunt the tissue sympathetic nervous system response in brown adipose tissue of cold-exposed mice.

Adipose Tissue, Brown

The topoisomerase II inhibitor teniposide (VM-26) induces apoptosis in unstimulated mature murine lymphocytes.

This study shows that not only concanavalin A-stimulated proliferating lymphocytes but also unstimulated mouse splenic lymphocytes are sensitive to the topoisomerase II (topo II) inhibitor teniposide (VM-26). When unstimulated lymphocytes are pretreated with VM-26 for a 2-h period and are then incubated in drug-free medium, cell viability, as determined by trypan blue exclusion, decreases to 40% of the control by 6 h. The drug-treated cultures show two to three times the level of detergent soluble DNA than the control cultures and agarose gel electrophoresis of the soluble DNA shows the presence of oligonucleosomal-sized fragments, a feature considered to be a hallmark of apoptosis. Phase contrast microscopy, Hoechst staining for DNA, and immunofluorescence microscopy of various nuclear and cytoplasmic antigens (nucleolar fibrillarin, snRNP, ubiquitin, vimentin, tubulin) in the VM-26-treated cells characterize the morphological changes during apoptosis of these cells. The role of topo II as the mediator of the VM-26 effects is supported by pulsed field gel electrophoresis, which shows the typical topo II-induced cleavage of supercoiled DNA into loop-sized 300- and 50-kbp fragments. We conclude that the cancer chemotherapeutic agent VM-26 interacts with topo II and induces apoptosis in unstimulated lymphocytes.

Animals

Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes.

The effects of topoisomerase II-reactive epipodophyllotoxins etoposide and teniposide as well as amsacrine on the viability of thymocytes in primary culture has been examined. All three drugs were shown to produce DNA cleavage detectable by resolving isolated DNA by pulsed field agarose gel electrophoresis. The DNA cleavage was found to have two components. The first was due to the interaction of the drugs with topoisomerase II, whereas the second component was due to endonuclease cleavage caused by the drug-induced entry of the thymocytes into programmed cell death or apoptosis. This second component of the DNA cleavage was also detected in thymocytes undergoing apoptosis following exposure to the glucocorticoid analogue, dexamethasone. The effect of the drugs on programmed cell death is dependent upon new protein and RNA synthesis, indicating that topoisomerase II has a role in the very first stages of the process. These results are discussed in terms of the use of this class of topoisomerase II-reactive drugs in chemotherapy.

Amsacrine

The involvement of the sympathetic nervous system in meal-induced thermogenesis in mice.

The acute effect of food intake on the activity of the sympathetic nervous system (SNS) in both heart and brown adipose tissue (BAT) was investigated in mice. Upon delivery to the laboratory mice were housed singly and divided into two groups. Half the mice were accustomed to eat their daily food ration in two meals whereas the other half were given continuous access to food. SNS activity in both heart and BAT was estimated by measuring the accumulation of dopamine (DA) after having blocked the transformation of dopamine into noradrenaline (NA) with 1-cyclohexyl-2-mercapto-imidazole (CHMI). CHMI inhibits the enzyme dopamine beta-hydroxylase. On the day SNS activity was assessed, continuously fed (CF) or meal-fed (MF) mice were injected with either saline or CHMI one hour before being killed. In order to assess the anticipatory effects of being fed, a group of mice already accustomed to the meal-feeding schedule were not allowed to eat after the injections. Additional CF and MF mice were killed without being injected in order to determine the basal levels of both DA and NA. The results show that the accumulation of DA in both heart and BAT was higher in MF than CF mice regardless of whether MF mice were or were not fed after the injection of CHMI. It therefore appears that the intake of food may increase SNS activity in various tissues in mice, and that such a response may be largely of cephalic origin.

Adipose Tissue

Periodicity of DNA folding in higher order chromatin structures.

Each level of DNA folding in cells corresponds to a distinct chromatin structure. The basic chromatin units, nucleosomes, are arranged into solenoids which form chromatin loops. To characterize better the loop organization of chromatin we have assumed that the accessibility of DNA inside these structures is lower than on the outside and examined the size distribution of high mol. wt DNA fragments obtained from cells and isolated nuclei after digestion with endogenous nuclease or topoisomerase II. The largest discrete fragments obtained contain 300 kbp of DNA. Their further degradation proceeds through another discrete size step of 50 kbp. This suggests that chromatin loops contain approximately 50 kbp of DNA and that they are grouped into hexameric rosettes at the next higher level of chromatin structure. Based upon these observations a model by which the 30 nm chromatin fibre can be folded up into compact metaphase chromosomes is also described.

Animals

[Isolated rectal ectasia: a rare cause of chronic constipation. Apropos of 2 cases].

We present two patients with intractable constipation, in which investigation revealed a huge rectal ectasia without apparent other anomaly. Findings at operation are similar to those observed in the focal ectasia of the terminal bowel that we have already described in some cases of low anal deformities. As long as the physiopathology of this anomaly is not elucidated, complete amputation of the rectum seems to be the treatment of choice.

Adolescent

Factors affecting cold acclimation and thermogenesis in man.

Three types of cold exposure are observed in man: systemic moderate cold (SM), systemic severe cold (SS), and local severe cold (LS). Contrary to rat, prolonged exposure to SM cold does not produce non-shivering thermogenesis, as it does in the rat, possibly because of lack of active brown adipose tissue. Instead there is a reduction in heat production, in shivering, and in discomfort through a process known as habituation. No adaptation was found with exposure to SS cold, since shivering and discomfort always prevail and there is indirect evidence of enhanced sympathetic response after repeated exposure to SS cold. Exposure to LS cold leads to adaptive responses in which discomfort and autonomic activity are reduced. It is suggested that LS adaptation is also related to habituation.

Acclimatization

Effects of cold acclimation, cold exposure, and palatability on postprandial thermogenesis in rats.

Groups of rats were maintained at 24 degrees C and 4 degrees C (WA, CA). At each temperature one group was fed a pelleted stock diet, while another was fed in addition, 3 kJ of palatable food at 1-h intervals for a total of 8 h during the day. After 2 weeks the thermogenic response to both 3 kJ and 30 kJ of palatable food was determined by measuring oxygen consumption over a period of 3 h. Food intake revealed two phases of postprandial thermogenesis. During the initial cephalic phase which lasted 30 min the O2 consumption increased by about 40 percent with both test meals and the response was comparable for WA and CA rats tested at the same temperature. During the subsequent gastrointestinal phase the response was proportional to the size of the meal and the CA rats were always more responsive than the WA rats specially when tested at 4 degrees C. The results suggest that postprandial thermogenesis during the initial cephalic phase is related to food palatability and that cold exposure and cold acclimation cause an enhanced response during the second phase of meal thermogenesis.

Acclimatization

Effects of exercise and intermittent cold exposure on shivering and nonshivering thermogenesis in rats.

The effects of both exercise training and intermittent cold acclimation on heat production (shivering and nonshivering thermogenesis (NST)) in rats were studied. Warm-acclimated rats (housed at 24 degrees C, WA) and intermittently cold-acclimated rats (exposed daily to -5 degrees C for 2 h, CA) were forced to run (25 m.min-1 for 1 h) every day (WA-T and CA-T). WA and CA left sedentary (WA-S and CA-S) served as controls. Norepinephrine (NE)-induced thermogenic capacity assessed from the increment of oxygen consumption (VO2) and colonic temperature (Tc) were measured 4 weeks after commencing acclimation and exercise training. The thermogenic capacity was greater in CA than in WA. However, in WA, WA-T responded to NE less than WA-S, whereas the response of CA-T and CA-S did not differ. Wet weight of interscapular brown adipose tissue (IBAT) and its protein (and dry matter--regarded to be highly representative of protein) content were larger in CA than in WA. Respective sedentary and exercised groups of rats had similar IBAT protein (and dry matter) content although tissue weight was lighter in WA-T than in WA-S. Lipid content of IBAT was also larger in CA than in WA. IBAT of WA-T had less lipid compared to that of WA-S while no difference was seen between CA-S and CA-T. Shivering activity during acute cold (4 degrees C) exposure was less in CA compared to WA and there was no difference between respective groups of exercised and sedentary rats. Propranolol, a blocker of NE-dependent NST, eliminated the difference in shivering among these four groups. When exposed to severe cold (-10 or -20 degrees C), the fall in Tc of rats fasted for 18 h was greater in WA than in CA. CA-T showed a greater decrease in Tc than CA-S during -20 degrees C exposure while it did not differ during -10 degrees C exposure. On the other hand, Tc of WA-T and WA-S did not differ significantly during either cold exposure period. These results suggest that exercise training in rats housed at 24 degrees C suppresses NE-dependent NST whereas another nonshivering thermogenic mechanism (NE-independent) may compensate this suppression. However, NE-dependent NST of WA-S and WA-T did not parallel protein (dry matter) content of IBAT; no difference existed in IBAT protein between these two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization

Thermogenesis with relation to exercise and exercise-training.

Exercise-training at environmental temperatures outside the thermal neutral zone, causes thermoregulatory adaptive reactions. In the heat, sweat efficiency is enhanced thus reducing the incidence of hyperthermia while in the cold discomfort and danger of frostbite are minimized by an improved cutaneous circulation specially in the extremities. Over long periods of time exercise does not affect thermogenesis except when refeeding. It is suggested that the reduced postprandial heat production reported in exercise-trained subjects is related to changes in nutrient metabolism which in turn could be related to insulin and norepinephrine modified actions.

Body Temperature Regulation

Energy balance in exercise-trained rats acclimated at two environmental temperatures.

The present study was carried out to investigate the effects of exercise training on energy balance in male rats acclimated at two different environmental temperatures. Sedimentary and exercised rats were housed and trained at either 24 or 4 degrees C, with the training program consisting of running on a motor-driven treadmill within their respective environments. After 45 days, energy, protein, and fat contents of rats were determined together with the energy content of food and feces. The results show that metabolizable energy intake was reduced by 10% in exercise-trained groups. Substantial differences in energy gains were observed between sedentary and trained rats; sedentary rats showed almost three times more energy gain than trained rats. Carcass analysis revealed the energy gain differences to be mainly due to varied amounts of fat deposition. Energy expenditure (kJ) excluding the cost of exercise training was corrected for metabolic body size (BW 0.75), which in turn showed no significant differences between trained rats and their respective sedentary controls. The present results suggested that exercise training in rats leads to neither increase nor decrease in energy expenditure through components additional to physical activity. The present results also indicated that brown adipose tissue thermogenesis, as assessed through mitochondrial guanosine 5'-diphosphate binding, was not significantly modified by exercise training, regardless of the temperature at which the rats were housed and trained.

Acclimatization

[Diagnostic and therapeutic use of human anti-D (Rho) monoclonal antibodies. Evaluation and perspectives].

Human monoclonal antibodies will be essential in medicine. They are valuable tools for biological diagnosis and therapeutics. Our model, human monoclonal antibodies directed against the Rhesus D antigen can be used for the determination of the Rhesus D phenotype and for the suppression of Rh(D) immunisation in women. These new products require new procedures of preparation, new regulations for the quality controls, which will be discussed in this paper.

Animals

Familial resemblance in maximal heart rate, blood lactate and aerobic power.

There are considerable interindividual differences in maximal oxygen uptake per kilogram of body weight (VO2 max/kg), maximal heart rate (max HR) and maximal blood lactate (max blood La) measured during a progressive exercise test. The aim of the study was to quantify the familial relationships for these variables. Parents and children of 38 families of French-Canadian descent were submitted to a modified Balke treadmill test. VO2 max/kg and max HR were the highest values reached during the test for 1 min. Max blood La was obtained from a blood sample taken 2 min after the test. The effects of age and sex were significant for max blood La and VO2 max/kg in each generation. Scores were thus adjusted through multiple regression procedures (age + sex + age X sex + age2), yielding residuals which were submitted to further analysis. Intraclass correlations (ri) were significant in pairs of sibs for max blood La and max HR, i.e. 0.28 (p less than 0.01) and 0.43 (p less than 0.05), respectively. For VO2 max/kg, pairs of spouses and sibs were about similarly correlated (ri = 0.20 and 0.15; p less than 0.05). Data suggested that children were more related to their mother than to their father for VO2 max/kg, VO2 max/kg of fat-free weight, and particularly for max HR. It was concluded that familial resemblance and heritability estimates for maximal aerobic power, max HR and max blood La were quite low and generally nonsignificant. Correlations between biological sibs were, however, consistently significant for max HR and max blood La. The suggestion of a maternal effect in maximal aerobic power should be further investigated.

Adolescent

[Is it still necessary to teach community psychiatry to the psychiatric resident?].

After having defined his conception of what community psychiatry is, where it is situated in the line of evolution of modern psychiatry, the author weighs the pertinence of teaching residents knowledge pertaining to a sector in full identity crisis. The effort is worthwhile, since this crisis has permitted the community psychiatrist to better define himself, namely in regard to the other health professionals, and it is therefore easier to determine what kind of knowledge should be transmitted to the resident in this particular field. A tentative teaching program is outlined. In such a program, education aspects should take precedence of training aspects, making the future psychiatrist more prepared to face eventual changes in that field. Such a program should take place in the final part of the residency course following a solid preparation in basic clinical psychiatric knowledge.

Community Psychiatry

Thermogenesis in relation to feeding and exercise training.

Tube-fed rats gain more weight than meal-fed rats when fed isocaloric diets. Human volunteers were fed on separate occasions isocaloric meals by mouth or by gavage and resting metabolic rate was measured for 90 min postprandially. Resting metabolic rate was greater in meal-fed than in tube-fed especially in the period following meal digestion. These results suggest that ingestion of food through sensory stimulation activates oxidative processes which may be under endocrine control. In tube-feeding where sensory inputs are absent, a reduction in meal thermogenesis is observed.

Animals