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Biomedical subjects

J P Robin

Publications and source records attributed to J P Robin.

At least 19 recordsLinked to original sources

Long-term fasting and re-feeding in penguins.

Spontaneous fasting during reproduction (sometimes with a full stomach) and moult is a major characteristic of the annual cycle of penguins. Long-term fasting (up to four months in male emperor penguins) is anticipated by the accumulation of fat (incubation fast) and of fat and protein (moult fast). During most of the incubation fast, birds rely almost entirely on lipids as an energy source, body proteins being spared. However, below a critical (but non-total) fat store depletion, marked behavioural, metabolic, and endocrine changes occur. Spontaneous locomotor activity increases and the egg is transitorily left unincubated for increasingly long periods, until its definitive abandon and the bird departs to re-feed at sea. These changes are thought to be activated by an endogenous re-feeding signal triggered before lethal energy depletion. An increase in body protein catabolism in the face of a reduction in lipid availability and utilisation, and an increase in circulating corticosterone vs. a decrease in plasma prolactin, are likely to be major metabolic and hormonal components of this signal. The survival and rapid restoration of energy stores in birds having departed to re-feed at a stage of near total lipid depletion demonstrates the effectiveness of the re-feeding signal. Penguins, and possibly other seabirds, are therefore appropriate animal models for understanding the long-term interactions between body energy reserves and fasting, breeding and feeding physiology and behaviour.

Animals↗

Determining body fuels of wintering mallards.

Measuring body lipids and proteins of wild animals such as mallards is essential to determine the impact of the environment on their body condition. A major difficulty, however, is that biochemical analysis of carcass is tedious and therefore cannot be applied at a large scale. The main objective of this study was therefore to find out if simple measurements can be used as indices of total body lipids and proteins. Four classes of lipid and protein indices, derived on a 'source' group, were defined according to their complexity and condition of application (field or laboratory). Accuracy of the indices was evaluated on an independent group, of which the body composition calculated from indices was compared to carcass analysis. In live birds, body mass was an accurate and convenient predictor for both lipid and protein masses. If carcasses are available, extensive analysis provides a higher accuracy for body lipids only. This can be simply obtained through multiple regressions using abdominal fat mass and/or dry body mass.

Animals↗

Refeeding signal in fasting-incubating king penguins: changes in behavior and egg temperature.

This study is directed toward understanding the process of feeding stimulation ("refeeding signal") that has been suggested to operate below a body mass threshold or critical metabolic status in spontaneously fasting birds. Behavior and egg temperature (T(egg)) were continuously monitored by video monitoring and biotelemetry, respectively, in fasting-incubating king penguins kept in a pen to prevent relief by the partner until spontaneous egg abandonment. Penned birds fasted 10 days more and lost 1.2 kg more than birds relieved normally by their partner, abandoning the egg about 1 wk after reaching a critical body mass. Definitive egg abandonment was preceded by transitory abandonments of progressively increasing duration during which time the birds went further and further away from their egg. There were marked interindividual differences but on average transitory abandonments began 36 +/- 5 h before the definitive abandonment and were paralleled by resumption of display songs signaling the readiness of the bird to depart for feeding. T(egg) was maintained at around 35.7 degrees C during normal incubation but significantly decreased the last 2 days before egg abandonment. These changes are interpreted as reflecting a stimulation to refeed at a threshold body mass corresponding to a critical fat store depletion. Thus the fasting-incubating king penguin appears to be an interesting animal model for understanding the long-term metabolic control of feeding behavior in relation to energy status.

Animals↗

Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers.

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.

Amino Acid Sequence↗

Acquired hemophilia due to factor VIII inhibitors in 34 patients.

BACKGROUND: Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS: We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS: The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION: This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.

Adult↗

Behavioral changes in fasting emperor penguins: evidence for a "refeeding signal" linked to a metabolic shift.

This study examines the relationships between metabolic status and behavior in spontaneously fasting birds in the context of long-term regulation of body mass and feeding. Locomotor activity, escape behavior, display songs, body mass, and metabolic and endocrine status of captive male emperor penguins were recorded during a breeding fast. We also examined whether body mass at the end of the fast affected further survival. The major part of the fast (phase II) was characterized by the maintenance of a very low level of locomotor activity, with almost no attempt to escape, by an almost constant rate of body mass loss, and by steady plasma levels of uric acid, beta-hydroxybutyrate, and corticosterone. This indicates behavioral and metabolic adjustments directed toward sparing energy and body protein. Below a body mass of approximately 24 kg (phase III), spontaneous locomotor activity and attempts to escape increased by up to 8- and 15-fold, respectively, and display songs were resumed. This probably reflected an increase in the drive to refeed. Simultaneously, daily body mass loss and plasma levels of uric acid and corticosterone increased, whereas plasma levels of beta-hydroxybutyrate decreased. Some experimental birds were seen again in following years. These findings suggest that at a threshold of body mass, a metabolic and endocrine shift, possibly related to a limited availability of fat stores, acts as a "refeeding signal" that improves the survival of penguins to fasting.

3-Hydroxybutyric Acid↗

Accumulated body burden and endogenous release of lead in employees of a lead smelter.

Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.

Adult↗

Evaluation of selenium exposure in copper refinery workers.

Concentrations of selenium in plasma and urine and activity of glutathione peroxidase in erythrocytes were determined in workers exposed to selenium and in a control group. Plasma selenium concentrations were significantly lower in exposed workers compared to the controls. Erythrocyte glutathione peroxidase activity in selenium workers was significantly higher than in the control subjects. Urine selenium concentrations were not statistically different between the two groups. There was a significant positive correlation between plasma selenium concentrations and urine selenium concentrations in workers exposed to selenium. A weak significant positive correlation was found between plasma selenium concentrations and erythrocyte glutathione peroxidase activity in exposed workers. Our results suggest that the lower plasma selenium concentrations in selenium workers may be attributed to an increase of urinary selenium excretion.

Adult↗

Involvement of corticosterone in the fasting-induced rise in protein utilization and locomotor activity.

During fasting, most of the energy is derived from lipids whereas proteins are efficiently spared. However, there is a late rise in net protein utilization. Fasting is also associated with an increase in locomotor activity. Because the plasma corticosterone level increases concomitantly with these metabolic and behavioral changes, the involvement of corticosterone has been hypothesized. To test this, the net protein utilization and locomotor activity were investigated in fasted adrenalectomized (Adx) rats, with or without replacement with corticosterone, and in fasted intact rats treated with RU486, an antagonist of type II glucocorticoid receptors. During the phase of fasting characterized by protein sparing, urine nitrogen loss was further reduced in Adx rats and in RU486-treated controls compared with intact rats and with Adx rats with corticosterone replacement: this indicates a catabolic effect of corticosterone through type II receptors. In the last phase of fasting, the rise in net protein breakdown was suppressed in Adx rats and restored by corticosterone replacement. The increase in locomotor activity induced by fasting in controls was suppressed in Adx and restored by corticosterone replacement. This rise in running activity was still present in RU486-treated rats. In conclusion, this study shows that corticosterone plays a critical role in the changes of both protein catabolism and locomotor activity during prolonged fasting.

Adipose Tissue↗

Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by a new synthetic demethylpodophyllotoxin derivative.

A newly synthesized demethylpodophyllotoxin derivative, 4-O-butanoyl-4'-demethylpodophyllotoxin (BDPT) or BN58705, has recently been shown to exert a potent cytotoxic activity in vitro against a variety of drug-resistant human tumor cell lines. The effect of this agent on effector cells of the immune system, however, has not been examined. The present study investigated the effect of BDPT on the response of activated human peripheral blood derived monocytes (PBM) to secrete cytokines. Activation of PBM overnight with LPS, IFN-gamma, or PMA resulted in secretion into the supernatant of TNF-alpha, IL-1 beta, IL-6, and IL-8 as assessed by ELISA. The addition of BDPT to the stimulated cultures resulted in significant inhibition of TNF-alpha and IL-1 beta secretion, whereas the secretion of IL-6 and IL-8 was not affected. The selective inhibition of TNF-alpha and IL-1 beta secretion by BDPT-treated PBM was observed with all three stimuli tested. The inhibitory effect mediated by BDPT was concentration dependent and was optimal at 6-20 microM. Time kinetic analysis indicated that the inhibition of secretion was rapid and detected as soon as 2 hr following stimulation of the PBM and lasted for as long as 24 hr. A comparison was made between BDPT and pentoxyfilline, a xanthine-derived phosphodisterase inhibitor that was reported to inhibit TNF-alpha and IL-1 beta secretion by PBM. Both BDPT and PTX showed similar time kinetics and patterns of inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Cytotoxic properties of a new synthetic demethylpodophyllotoxin derivative, BN 58705, against human tumor cell lines.

The in vitro cytotoxic properties of a newly synthesized demethylpodophyllotoxin derivative, 4-o-butanoyl-4'-demethylpodophyllotoxin (BN 58705), were determined by using several human tumor cell lines of different histological origin and of different sensitivity to conventional chemotherapeutic drugs (Adriamycin and cis-diammine-dichloride platinum). BN 58705 is shown to be cytotoxic against various human tumor cell lines as assessed by the MTT assay. Furthermore, BN 58705 is shown to be cytotoxic against several drug-resistant tumor cell lines. BN 58705 is cytotoxic at concentrations 100- to 1000-fold lower than those of Adriamycin or cis-diammine-dichloride platinum required to achieve similar cytotoxicity. BN 58705 did not mediate DNA fragmentation of target cells, whereas the epipodophyllotoxin-like etoposide induced DNA cleavage by stabilizing the DNA-enzyme intermediate. Like vinca alkaloids, BN 58705 induced a block in the mitotic phase of the cell cycle. By comparison, BN 58705 exerted a stronger cytotoxic activity in vitro than did either etoposide, an epipodophyllotoxin, or vincristine, a vinca alkaloid. When BN 58705 was applied in vivo in mice, it resulted in low toxicity (50% lethal dose, 150 mg/kg). These results demonstrate than BN 58705 is cytotoxic to drug-resistant human tumor cell lines and is manyfold more potent than conventional drugs. The cytotoxic potency and low toxicity of BN 58705 are important criteria to establish its potential chemotherapeutic efficacy in vivo.

Animals↗

[Malacoplakia. Apropos of a case of retroperitoneal site].

Malacoplakia is a granulomatous inflammatory disease caused by a disorder of macrophage bactericidal function. The disease, histologically characterized by the presence of Michaelis-Gutmann bodies, has a preference for the urogenital tract and less frequently affects the gastrointestinal tract and the retroperitoneal region. We report the unusual case of a male patient who presented with retroperitoneal pseudotumoral malacoplakia associated with vesical malacoplakia. The main pathophysiological, diagnostic and therapeutic aspects of this rare disease are described.

Adult↗

Relationships between lipid availability and protein utilization during prolonged fasting.

Mammals and birds adapt to prolonged fasting by mobilizing fat stores and minimizing protein loss. This strategy ends with an increase in protein utilization associated with behavioural changes promoting food foraging. Using the Zucker rat as a model, we have investigated the effect of severe obesity on this pattern of protein loss during long-term fasting. Two interactions between the initial adiposity and protein utilization were found. First, protein conservation was more effective in obese than in lean rats: fatty rats had a three times lower daily nitrogen excretion and proportion of energy expenditure deriving from proteins, and a lower daily protein loss in various muscles. This phase of protein sparing is moreover nine times longer in the fatty rats. Second, obese animals did not show the late increase in nitrogen excretion that occurred in their lean littermates. Total body protein loss during starvation was larger in fatty rats (57% versus 29%) and, accordingly, total protein loss was greater in their muscles. At the end of the experiment, lean and obese rats had lost 98% and 82%, respectively, of their initial lipid reserves, and fatty rats still had an obese body composition. These results support the hypothesis that in severely obese humans and animals a lethal cumulative protein loss is reached long before the exhaustion of fat stores, while the phase of protein conservation is still continuing. In contrast, in lean rats, survival of fasting seems to depend on the availability of lipid fuels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Stress in birds due to routine handling and a technique to avoid it.

The stress that might result in animals from the routine handling that most experimental studies involve, e.g., weighing, injecting, and blood sampling, is usually assumed to be minimal when the animals look quiet. However, the intensity of this stress remains largely ignored. We have developed a system that allows blood samples to be taken from freely behaving geese without entering the animal room. In these entirely undisturbed geese, the humoral indexes of stress, i.e., blood levels of catecholamines, corticosterone, and lactate, were as low or even lower than the lowest values previously reported for birds. Remarkably, the mean basal values for epinephrine and norepinephrine were 90-fold and 5-fold, respectively, below the lowest values in the literature. Stress-induced variations in pH that would have concealed detection of nutrition-induced changes in pH were eliminated. In contrast, even though the birds looked quiet during a short 5-min routine handling procedure, to which they had been accustomed for weeks, there was a dramatic increase in the level of humoral indexes of stress. These increased severalfold within only 2 min, and the return to initial values could take up to 1 h. Acid-base balance was also disrupted. Thus, in studies on animals, the absence of stress cannot be deduced from only behavioral observations. Only a system for taking blood without human interference may enable stress-free investigations.

Adaptation, Psychological↗

Daily pattern of melatonin secretion in an antarctic bird, the emperor penguin, Aptenodytes forsteri: seasonal variations, effect of constant illumination and of administration of isoproterenol or propranolol.

Daily variations in circulating melatonin concentrations have been measured at monthly intervals from April to December 1986 in an Antarctic bird, the emperor penguin, Aptenodytes forsteri, maintained under natural conditions. Both duration of the elevated nighttime melatonin levels and amplitude of the day-night rhythm displays an annual variation closely related to variations in the daylength. Duration of the nocturnal peak of melatonin secretion depended upon the duration of the darkness, decreasing with increasing daylength and disappearing completely during the summer solstice. The duration of the nighttime melatonin peak melatonin increased inversely with decreasing daylength. The amplitude of the day-night rhythm decreased in such a way that the nocturnal peak of melatonin completely disappeared during the winter solstice. Three days of constant illumination in September did not suppress the nighttime peak of melatonin secretion. The response of melatonin secretion, decreasing after beta-adrenergic agonist treatment and increasing after antagonist treatment, reinforces the hypothesis that in birds the regulation of melatonin synthesis differs from that of the rat. Receptors other than beta receptors may be involved.

Animals↗

Fasting-induced rise in locomotor activity in rats coincides with increased protein utilization.

The aim of this study was to investigate the possible relation between the modifications in locomotor activity (on running wheel) which occur during prolonged fasting and changes in the utilization of energy reserves. In 18-week-old rats, we found that the rate of body mass loss reflects the changes in nitrogen excretion that occur over three phases of fasting: (I) initially decreasing, (II) maintained at a low level and (III) increasing. Locomotor activity started to increase during phase II without a change in its nycthemeral pattern. By contrast, the 10-fold higher daily locomotor activity that occurred in phase III was marked by a higher proportion of diurnal activity. Using 9-, 18-, and 33-week-old rats, in order to obtain a different timing in the metabolic changes during fasting, we could confirm the coincidence between the later rise in locomotor activity and the occurrence of phase III. Refeeding of rats of either age in phase III rapidly suppressed fasting-induced changes in locomotor activity. These data accord with the idea that behavioral changes reflecting the search for food are triggered by a later and reversible change in the utilization of body protein vs. lipid stores during prolonged fasting.

Animals↗

Whole-body and tissue protein synthesis during brief and prolonged fasting in the rat.

1. Little information is currently available on protein turnover during chronic protein loss situations. We have thus measured the whole-body and tissue protein fractional synthesis rates (ks), the whole-body fractional protein degradation rate (kd), the capacity for protein synthesis (Cs) and the efficiency of protein synthesis (kRNA) in vivo in fed and fasted (1, 5 and about 9 days) 400 g rats. 2. One day of starvation resulted in a reduced ks and an increased kd in the whole body. ks was selectively depressed in skeletal muscles, mainly owing to a reduced kRNA, and was not modified in heart, liver and skin. The contribution of skin to whole-body protein synthesis increased by 39%. 3. During the phase of protein sparing (5 days of fasting), kd in the whole body decreased below the control fed level. ks in skeletal muscles was sustained because kRNA was restored to 82-98% of the control value. 4. Rats were in a protein-wasting phase after 9 days of starvation. kd in the whole body did not increase and was actually 78% of the value observed in fed animals. By contrast, ks in the whole body and tissues decreased to 14-34% of the control values, owing to reductions in both Cs and kRNA. Whatever the duration of the fast, the contribution of the skin to whole-body protein synthesis largely exceeded that of skeletal muscle. 5. The present findings suggest that the main goal in the treatment of chronic protein loss should be to sustain protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Carbamoyl phosphate biosynthesis and partition in pyrimidine and arginine pathways of Escherichia coli. In situ properties of carbamoyl-phosphate synthase, ornithine transcarbamylase and aspartate transcarbamylase in permeabilized cells.

A procedure for the permeabilization of Escherichia coli cells was adapted to the in situ determination of the catalytic and regulatory properties of the enzymes responsible for the biosynthesis of carbamoyl phosphate and its utilization in the pyrimidine and arginine pathways. Differences in enzyme sensitivity to effectors and changes in pH dependence were observed. Partition of carbamoyl phosphate in the two metabolic pathways could be measured under conditions of substrate saturation. The results obtained will allow to test experimentally the theoretical predictions made by A. Goldbeter (1973) PhD thesis, Université Libre de Bruxelles, on the distribution of carbamoyl phosphate and the oscillation of its intracellular concentration.

Arginine↗