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Biomedical subjects

J LeBlanc

Publications and source records attributed to J LeBlanc.

At least 37 records · Page 2Linked to original sources
PubMed1997

Evidence that DNA fragmentation in apoptosis is initiated and propagated by single-strand breaks.

Apoptosis is characterised by the degradation of DNA into a specific pattern of high and low molecular weight fragments seen on agarose gels as a distribution of sizes between 50-300 kb and sometimes, but not always, a ladder of smaller oligonucleosomal fragments. Using a 2D pulsed field-conventional agarose gel electrophoresis technique, where the second dimension is run under either normal or denaturing conditions, we show that single-strand breaks are introduced into DNA at the initial stages of fragmentation. Using single-strand specific nuclease probes we further show that the complete fragmentation pattern, including release of small oligonucleosomal fragments can also be generated by a single-strand endonuclease. Three classes of sites where single-strand breaks accumulate were identified. The initial breaks produce a distribution of fragment sizes (50 kb to >1 Mb) similar to those generated by Topoisomerase II inhibitors suggesting that cleavage may commence at sites of attachment of DNA to the nuclear matrix. A second class of rare sites is also cut further reducing the size distribution of the fragments to 50-300 kb. Thirdly, single-strand breaks accumulate at the linker region between nucleosomes eventually causing double-strand scissions which release oligonucleosomes. These observations further define the properties of the endonuclease responsible for DNA fragmentation in apoptosis.

Journal Article↗
PubMed1997

A possible role for palatability of the food in diet-induced thermogenesis.

OBJECTIVE: A regulatory increase in energy expenditure, induced by excess intake of palatable food (cafeteria diet), is well documented. It has also been shown that excess feeding by gastric intubation, fails to enhance thermogenesis, suggesting that the palatability of the food could have a role in producing this regulatory response. A study was planned to find out if a palatable diet pair-fed with standard laboratory chow would produce diet-induced thermogenesis (DIT) and if the brown adipose tissue (BAT) was involved in this process. DESIGN: Body weight gain, BAT activity and body temperature response to norepinephrine were measured in rats fed for 40 d either the standard laboratory pellets (control), a palatable high carbohydrate diet fed ad libitum and the same palatable diet but fed in restricted amounts to match the intake of the control group. RESULTS: It was found that palatable food either fed ad libitum or pair-fed, increased DIT and reduced food efficiency (which is the body weight gain per 100 kj of food consumed). These responses were paralleled by increased BAT activity and enhanced response to noradrenaline. Since the DIT with pair-feeding was proportionally as large as with excess intake of the same food in the group fed ad libitum, it is concluded that the palatability of the food, rather than the excess intake per se, is responsible for the increased thermogenesis. CONCLUSIONS: DIT was observed when palatable food was fed either ad libitum or in restricted amounts. It is suggested that the palatability of the diet rather than the quantity or composition of the ingested food is responsible for the DIT. It is also proposed that the excess energy expenditure due to sensory stimulation induced by palatable food, is directly related to an enhanced sympathetic activity which stimulates the BAT thermogenic capacity.

Adipose Tissue, Brown↗
PubMed1997

Heterogeneous Serratia marcescens genotypes from a nosocomial pediatric outbreak.

OBJECTIVE: Define the applicability of a rapid molecular typing scheme to study the epidemiology of a Serratia marcescens outbreak. DESIGN: With the assistance of a simple bacterial lysis technique, isolates of S marcescens from a putative outbreak were genotyped with the polymerase chain reaction technology for which primers were chosen on the basis of previously defined enterobacterial repetitive intergenic consensus sequences. SETTING: Pediatric ICU. PATIENTS: Intensively monitored patients who were found to yield S marcescens from any body site during the epidemic period. RESULTS: Over an 8-month period, 12 ICU patients were either infected or colonized with S marcescens. All of these patients were transiently supported by artificial ventilation. During the epidemiologic investigation, a dilution error in a high-level glutaraldehyde disinfectant, which was being used for some ventilator components, was observed. Rectification of the error was associated with an abrupt termination of the outbreak. Enterobacterial repetitive intergenic consensus polymerase chain reaction was easily applicable to this setting and it defined 4 distinct genotypes among the 12 isolates. CONCLUSION: The typing method is easily implemented and offers great promise as an epidemiologic tool. The associated investigation served to emphasize that an outbreak may occur with more than one epidemic strain and that strain heterogeneity itself does not exclude an outbreak.

Bacterial Typing Techniques↗
PubMed1996

Early insulin and glucagon responses to different food items.

An early postprandial insulin release has previously been described when high carbohydrate meals are fed. The present investigation on humans shows that this response takes place not only with high carbohydrate (sugar pie) but also with high lipid (whipped cream) and protein (beef steak or fish fillet) meals, suggesting that it is caused by the palatability of the food rather than to its composition. This increment takes place at the very beginning of the meal and even if the period of feeding lasted 10 min, the response has disappeared at that time. Thirty min later due to plasma glucose elevation, a significant increase in insulin was observed with the sugar pie. At that time a similar increase was observed with the fish filet or the beef steak but not with the whipped cream. A cephalic glucagon response was not observed with any of the meals but 30 min after feeding the plasma level of this hormone increased with both beef and fish feeding and decreased significantly with the sugar pie meal. The usefulness of these responses is discussed with relation to the metabolic responses associated with feeding.

Adult↗
PubMed1996

Interactions between postprandial thermogenesis, sensory stimulation of feeding, and hunger.

An early thermogenic response has been described following the ingestion of palatable food. This study was designed to investigate the possible relationship between this so-called cephalic response, the sensory stimulation of feeding, and the declining feeling of hunger as the meal progresses. O2 consumption, carbohydrate and lipid oxidation, as well as ratings of hunger were measured in four experimental situations in which the subjects, after overnight fast, ate either two small caramel cakes at one time or the same amount of calories divided in eight portions that were eaten at 10-min intervals. The third experiment, the sham-feeding experiment, was similar to the last one except that the food was spit out instead of being swallowed after being chewed. A control experiment was added in which no food was given but during which the subject mimicked the act of chewing as was done in the preceding experiment. A small increase in O2 consumed was observed in the control experiment. After the one-meal experiment, the increase was larger for the first 90 min and declined thereafter. During the first 40 min of the sham-feeding experiment, O2 consumption increased more than when the eight meals were eaten, indicating that during this period the sensory stimulation per se is responsible for the cephalic thermic response to food. At 90 min, the ratings of hunger were diminished not only in the eight meals experiment but in the eight sham meals experiment as well, showing the role of sensory stimulation in the control of hunger. These results indicate a possible causal relationship between the cephalic thermogenesis, the control of hunger, and the prandial sensory stimulations.

Adult↗
PubMed1994

Endonuclease activities associated with high molecular weight and internucleosomal DNA fragmentation in apoptosis.

We have used pulsed-field gel electrophoresis and electron microscopy to correlate stages of DNA fragmentation with alterations of nuclear structure during apoptosis. DNA fragmentation occurs in two stages. The first is initiated by a previously undescribed endonucleolytic activity that cleaves DNA into 50- to 300-kb fragments. Electron microscopy showed that this degree of cleavage was sufficient to cause the chromatin to undergo condensation. The second stage of fragmentation is catalyzed by the previously described calcium-magnesium endonuclease. The enzyme activity responsible for the initial fragmentation of DNA was found to be distinct from that causing subsequent internucleosomal DNA cleavage based upon its cation requirements, independence of proteolysis and lack of inhibition by zinc. Both activities were found to preexist in nuclei from thymocytes, liver, HL60, and IL2-dependent CTLL cells. Thus, in apoptosis DNA degradation involves two distinct endonucleolytic activities, with only the first activity being essential for cell death.

Animals↗
PubMed1994

Hormonal dose-response to an adenosine receptor agonist.

The effect of various doses of i.p. injection of the adenosine receptor agonist (R)-phenylisopropyladenosine (R-PIA), ranging from nanomolar to micromolar concentrations, on plasma levels of free fatty acids, glucose, insulin, glucagon, ACTH, and corticosterone was examined in 200-g male rats. At the lowest dose of R-PIA (0.005 mumol/kg), a marked decrease in plasma insulin and free fatty acids was observed. This effect on free fatty acids persisted up to the highest concentration of R-PIA (50 mumol/kg). The insulin response showed a similar pattern except at the highest concentration, when the plasma levels were within normal ranges. A 100% increase in plasma glucose was found, but only with doses of 0.5 mumol/kg and above, suggesting an A2 receptor influence, possibly related to the elevation of plasma glucagon observed with the same doses of R-PIA. It has been shown that caffeine, an antagonist of adenosine, stimulates the pituitary--adrenal axis. Surprisingly, it was shown that R-PIA produces the same effect, as evidenced by the marked elevation of both plasma ACTH and corticosterone at concentrations of 0.5 mumol/kg and higher. It is suggested that this centrally mediated effect is due to a primary peripheral action.

Adrenocorticotropic Hormone↗
PubMed1994

Imaging of mediastinal foregut cysts.

This study was undertaken to determine the value of magnetic resonance imaging (MRI) in the diagnosis of mediastinal foregut cysts. The MRI scans of 56 patients (with a total of 57 mediastinal masses) were reviewed. The patients (26 women and 30 men) had been examined between March 1986 and April 1991 at a tertiary-care hospital. T1-weighted and T2-weighted spin-echo images were available in all cases. The signal intensity of the lesions was compared with that of normal fat and muscle; the size, shape and location of the mediastinal masses were also noted. The 57 lesions consisted of 15 lymphomas, 10 neurogenic tumours, 10 thyroid masses, 6 thymomas, 6 foregut cysts and 10 other masses. Forty-eight of the masses had a signal intensity similar to that of muscle in T1-weighted images and higher than, equal to or lower than that of fat in T2-weighted images. Nine of the masses appeared bright in T1-weighted images, and the signal intensity was less than or equal to that of fat. Of these, four were foregut cysts and five were lymphomas. Of the six foregut cysts, four had short T1 values (the signal intensity ratio for cyst to fat ranging from 0.78 to 0.98) and long T2 values; two had the characteristic appearance usually associated with cystic lesions containing serous fluid--long T1 and T2 values. All of the foregut cysts appeared to be of soft-tissue attenuation on computed tomography (CT), all were located in the middle or posterior mediastinum, and all were round or oval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Surgical management and radiological characteristics of bronchogenic cysts.

Forty-two patients with bronchogenic cysts were treated over a 30-year period (1962 to 1991). The location was mediastinal in 37 and intrapulmonary in 5. Cysts were symptomatic in 21 patients (50%) and complications occurred in 11 (26%). The complications included infection in 5 patients, hemorrhage into the cyst in 2 patients, dysphagia due to esophageal compression in 2, adenocarcinoma arising from a bronchogenic cyst in an 8 1/2-year-old girl, and an esophagobronchopleurocutaneous fistula as a result of previous incomplete resection in 1 patient. Magnetic resonance imaging has been found to provide specific diagnostic information about bronchogenic cysts. All but 2 patients were treated with complete excision. One patient was managed by observation and another had drainage of the cyst by mediastinoscopy. Complications of treatment occurred in only 2 patients. One had a minor wound infection and the other had Clostridium difficile enterocolitis. Only 4 patients were lost to follow-up. No late complication or recurrence developed in those patients having complete excision. We recommend complete excision in most instances to confirm the diagnosis, relieve symptoms, and prevent complications.

Adolescent↗
PubMed1993

Components of postprandial thermogenesis in relation to meal frequency in humans.

Experiments on dogs have shown that the size of the meal has no effect on the early cephalic postprandial thermogenesis, and that four small meals are more thermogenic than a larger meal with the same total caloric content as the four meals. A study was repeated on human subjects who were fed during alternating weeks either one large meal (653 kcal (1 kcal = 4.1855 kJ)) or four small meals (163 kcal) at 40-min intervals. Oxygen consumption and respiratory exchange ratio determinations indicated (i) larger overall increase in postprandial thermogenesis with the four meals than with one meal and (ii) an enhancement of glucose utilization with the large meal compared with greater lipid utilization with the four meals. On the basis of indirect evidence from previous investigations it is suggested that the enhanced thermogenesis observed in the four-meal experiment is due to lipid mobilization caused by repeated stimulation of the sympathetic nervous system with palatable food. Blood analysis indicated a reduced elevation of plasma glucose in the four-meal experiment. The variations of insulin and C-peptide exactly paralleled those observed for glucose. It is concluded that the increased frequency of feeding significantly reduces insulin secretion in subjects fed a relatively high carbohydrate meal. In addition to this beneficial effect, increasing the number of meals increased thermogenesis and fat utilization.

Adult↗
PubMed1993

Detection of the initial stages of DNA fragmentation in apoptosis.

DNA fragmentation during apoptosis proceeds through an ordered series of stages commencing with the production of DNA fragments of 300 kbp, which are then degraded to fragments of 50 kbp. The 50-kbp fragments are further degraded, in some but not all cells, to smaller fragments (10-40 kbp) and release the small oligonucleosome fragments that are recognized as the characteristic DNA ladder on conventional agarose gels. Methodology is presented for the detection of the initial stages of DNA fragmentation using pulsed-field gel electrophoresis or a combination of pulsed-field gel electrophoresis and conventional agarose gel electrophoresis that allows detection of the DNA ladder in the same sample. A new method for the detection of high molecular weight DNA fragments on conventional agarose gels is presented, together with a rationale for the analysis of DNA fragmentation during apoptosis.

Animals↗
PubMed1992

Mechanisms of adaptation to cold.

The animal model used the most frequently for understanding the mechanisms of adaptation to cold in humans has been the rat. It has been established that rats kept in the cold for a few weeks stop shivering while preserving a normal internal temperature because of an enhanced thermogenic capacity of the brown adipose tissue (BAT) mediated by the sympathetic nervous system. Studies on groups of humans exposed to cold have shown that shivering is also attenuated but without compensatory increased in heat production possibly because of non-significant contribution of the BAT. However when humans and laboratory animals are exposed repeatedly to short severe cold evidence for adaptation has been described. This adaptation is not metabolic; instead it is related to the phenomenon of habituation. When exposed to a novel stress such as cold, the alarm reaction is initiated as evidenced by the activation of the sympathetic nervous system which opposes the stressing situation. However with time, when it is realized that the normal functioning of the body is not endangered the responses are attenuated and enhanced tolerance is observed. This type of adaptation was observed in Eskimos, fishermen, outdoor workers, etc.

Adaptation, Physiological↗
PubMed1992

Cold wind stimulation reflex.

The bradycardia induced by cold wind blown on the face and the early cephalic release of insulin induced by feeding have been shown to be caused by a vagal reflex stimulation. An experiment was designed to determine whether cold wind blown on the face would induce both pancreatic and cardiac stimulation. A 4 degrees C wind blown on the face for 4 min produced a rapid and persistent bradycardia, which interestingly persisted for up to 35 min after the test. The effect on respiration rate is more gradual and vanishes immediately after cold wind stimulation. Cold wind produced a slight reduction of insulin secretion, as evidenced by the fall of both plasma insulin and C-peptide, and caused a significant increase in plasma norepinephrine. These results suggest that the cold wind action of the vagus nerve is exerted on the heart and that of the sympathetic on the pancreas, whereas during the cephalic phase of feeding a vagal influence is observed on the pancreas and a sympathetic action on the heart. The mechanisms of the quantitative and qualitative control of these autonomic responses are not known and deserve further investigation.

Adult↗
PubMed1991

Thermogenic and hormonal responses to palatable protein and carbohydrate rich food.

Simultaneous variations of oxygen consumption, and plasma insulin and norepinephrine were measured during the postprandial cephalic and gastrointestinal phases of feeding in six human subjects following the ingestion of various nutrients. On alternative days the subjects were given foods (1280 kjoules) either rich in carbohydrates (sugar pie) or in proteins (fish). Both nutrients produced an initial (0-40 min) enhanced thermogenesis and an early (2 min) cephalic insulin release. During that period, elevations of plasma norepinephrine were also observed with pie feeding at 10 and 30 min and at 10 min with fish. Palatability ratings indicated that both food items were equally tasting. During the gastrointestinal phase (40 to 120 min) the variations of these same parameters including glucagon seem to be explained by the content in carbohydrates and proteins in the food rather than by its palatability. Indeed during that period the protein meal was more thermogenic and the carbohydrate meal induced the expected insulin secretion. These results suggest that the palatability of the food is responsible for the early cephalic increase in postprandial thermogenesis, and for the insulin and norepinephrine release. During the subsequent gastrointestinal phase the increased thermogenesis is related to the composition of the food which exerts its action by the biochemical processes involved in the disposal of the absorbed nutrients.

Adult↗
PubMed1991

Effect of patient positioning after needle aspiration lung biopsy.

Fifty-five patients who underwent fluoroscopically guided needle aspiration lung biopsy were randomly assigned to one of two postbiopsy treatment groups: Patients were placed recumbent with puncture site either down (n = 36) or up (n = 19) for at least 1 hour. No significant difference in pneumothorax rate was seen between the two groups. Chest tube placement, however, was required in 21% (four of 19) of the puncture-site-up group versus 3% (one of 36) of the puncture-site-down group, which was a significant difference (P = .04). Puncture-site-down postbiopsy positioning reduces the proportion of patients requiring chest tube placement after lung biopsy.

Biopsy, Needle↗