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Biomedical subjects

S Robert

Publications and source records attributed to S Robert.

At least 37 records · Page 2Linked to original sources

The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster.

The Drosophila Polycomb group (PcG) of genes is required for the epigenetic regulation of a number of important developmental genes, including the homeotic (Hox) genes. The members of this gene family encode proteins that do not share sequence similarity, implying that each plays a unique role in this epigenetic repression mechanism. Polycomblike (Pcl) was the second PcG gene to be identified. We report here the isolation and characterization of a human cDNA, termed PHF1, which encodes a protein with significant sequence similarity to Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL includes the two PHD fingers (C4-H-C3 motif), the region between them, and sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this 258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ hybridization. While several genetic diseases that are likely to result from developmental abnormalities map to this region, PHF1 is not a clear candidate gene for any of them.

Amino Acid Sequence↗

Bromocriptine given orally to periparturient of lactating sows inhibits milk production.

Gilts were assigned as controls (CTL, n = 6) or received orally 10 mg of bromocriptine thrice daily from d 110 of gestation until farrowing, (BRPP, n = 7), from d 1 to 6 postpartum (PP) (BRL1, n = 6), from d 7 to 13 PP (BRL2, n = 7), from d 14 to 20 PP (BRL3, n = 6), or from d 21 to 27 PP (BRL4, n = 6). Weights of pigs were recorded at birth, 24 h later, and on d 7, 14, 21, 28, 31 (weaning), 42, and 56 PP. Jugular blood samples were collected from sows on d 109 of gestation and every other day until farrowing, as well as on d 1, 6, 13, 20, and 27 PP. Behavioral observations of sows and litters were taken every 3 min for a 24-h period beginning 48 h after the onset of the treatments. In experimental sows, bromocriptine induced marked reductions in prolactin levels during treatment (P < .001). Compared to CTL sows, concentrations of IGF-I were higher at d 21 (P = .01) and 28 (P = .003) PP in BRL3 and BRL4 sows, respectively. In bromocriptine-treated sows, weight gain of litters was either drastically reduced or abolished (P < .001) during the week of treatment. Treatments also altered significantly the suckling behavior of pigs at all stages studied. Therefore, the present results strongly suggest that prolactin is essential for the initiation and the maintenance of milk production in sows. Results also indicate that prolactin does not seem to be involved in the maintenance of lactational anestrus during a 4-wk lactation.

Administration, Oral↗

Crystallization of monoacylated proteins: influence of acyl chain length.

The crystallization of monoacylated proteins has been investigated using a model system. Acylated derivatives of bovine pancreatic ribonuclease A, differing in their acyl chain lengths (10 to 16 carbon atoms), have been prepared using reverse micelles as microreactors. With one fatty acid moiety per polypeptide chain, covalently attached to the NH2 terminus of the protein, all the modified proteins have similar enzymatic activity and hydrodynamic radius as the native protein. Only the caprylated derivative can give crystals which diffract to high resolution. The resolved structure indicates that: (i) the protein folding is not modified by the chemical modification, (ii) the capryl moiety is not buried within the molecule but available for external interactions. Dynamic light scattering experiments on concentrated solutions show that the protein-protein interactions are dependent on acyl chain length. Proteins with the longest attached chains (14 and 16 carbon atoms) tend to self-associate through acyl group interactions.

Acylation↗

The Drug Utilization Review Network of Quebec.

Drug utilization review programs have been recognized as an effective way to control health care spending while maintaining quality services. This article describes the structure, mandate and activities of Quebec's Drug Utilization Review Network. This 112-member network, which represents 45% of health care facilities in the province, was established to promote the optimal utilization of drugs through the provision of support to pharmacology committees, therapeutic committees and pharmacy departments. The network's main role is to coordinate multi-centre drug utilization studies. Future challenges include maintaining member interest and evaluating the clinical and economic impact of the network's efforts.

Cost Control↗

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man.

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.

Adult↗

SES differentials in health by age and alternative indicators of SES.

Despite the general persistence and even increase of strong socioeconomic status (SES) differentials in health in the United States, research suggests that SES differentials in health may diminish or become nonexistent at older ages. However, most research has used only limited measures of SES (e.g. education, income), and has not thoroughly investigated intra-elderly age differences in this trend. The current study investigates how SES differentials in health vary by age in the United States, using fairly detailed age categories (through ages 85+), and 2 alternative indicators (home ownership and liquid assets) of a major additional dimension of SES, financial assets, which may be especially important at older ages. We address (a) how strongly financial assets are associated with health, considered both alone and net of education and income; (b) if the health effects of financial assets vary by age; and, more specifically, (c) if their effects are especially pronounced in older age, again considered both alone and net of or relative to education and income. Results show that financial assets, especially liquid assets, considered both alone and net of education and income, are associated with health throughout adulthood and old age, at least until ages 85+. Furthermore, financial assets remain associated with health until quite late in life and become more important relative to education and income at older ages for some measures of health.

Adult↗

Aprotinin.

OBJECTIVE: To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). DATA SOURCES: A MEDLINE search was used to identify French- and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. CONCLUSIONS: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.

Aprotinin↗

Transcription of the TATA binding protein gene is highly up-regulated during spermatogenesis.

TATA-binding protein (TBP) and its associated factors are required for transcriptional initiation by all three RNA polymerases, and evidence for regulation of their activities during early development has been recently reported. In the present study, we have investigated the regulation of TBP gene expression during male germ cell development. TBP mRNA was found to be increased more than 40-fold in rat and mouse testis and spermatogenic cells relative to somatic tissues. This up-regulation was stage-dependent, occurring specifically in meiotic and postmeiotic cells. Nuclear run-on analysis further demonstrated that transcription of the TBP gene was markedly elevated in the adult mouse testis relative to somatic tissue and prepuberal testis, indicating that transcriptional induction accounts, in large part, for the increased abundance of TBP mRNA in spermatogenic cells. In contrast to TBP mRNA, levels of TBP protein were elevated only 2.5-fold in mouse spermatogenic cells relative to somatic tissues. Polysome gradient analysis suggested that translational repression is an important determining factor in the unexpectedly low ratio of TBP protein-mRNA in male germ cells. These findings raise the possibility that transcriptional induction of TBP during spermatogenesis reflects a cell-specific homeostatic mechanism that maintains TBP protein concentrations at sufficiently high levels throughout male germ cell development.

Animals↗

Lactation performance of sows fed a bulky diet during gestation and receiving growth hormone-releasing factor during lactation.

Forty-eight crossbred gilts were used in an experiment with a 2 x 2 x 2 factorial arrangement of treatments. Treatments were control or bulky diet during gestation (4.1 vs 15.3% crude fiber), number of meals served daily in lactation (2 vs 4), and three daily s.c. injections of saline or of 1 mg of a human growth hormone-releasing factor analog (GRF-AN) from d 3 to 29 of lactation. Weights of pigs were recorded weekly until weaning on d 33. On d 29 of lactation, milk yield was estimated and a milk sample was obtained the next day. Jugular blood samples were collected from the sows on d 3 and 28 of lactation. Feed and water intake of sows were recorded throughout the study. Feeding the bulky diet decreased water intake in gestation (P < .001) and increased feed intake in lactation (P < .03). The number of meals served daily had no effect on feed intake during lactation (P > .1). Injections of GRF-AN increased IGF-I concentrations in blood (P < .01) and in milk (P < .001) and decreased backfat thickness (P < .001) and feed intake (P < .001) of sows during lactation. Pigs from sows injected with GRF-AN weighed more on d 14 (P < .05) and had a tendency to weigh more on d 7 (P = .09) and d 21 (P = .06). The incidence of sows showing estrus within 10 d of weaning was reduced with exogenous GRF (P < .01). The use of exogenous GRF in lactating sows may therefore have beneficial effects on growth of the pigs, yet the optimal nutritional and hormonal conditions needed for GRF to exert its full potential still need to be determined.

Animals↗

Serum concentrations of micronutrients, packed cell volume, and blood hemoglobin during the first two gestations and lactations of sows.

The objective of the present work was to describe the changes in serum concentrations of some micronutrients during the first 2 gestations and lactations of 33 gilts in order to establish blood reference values for a rapid assessment of nutritional status. In both parities, blood samples were taken from the jugular vein at mating, 5, 10 and 15 wk of gestation and l d and 4 wk after parturition (weaning). Reference values (mean, standard deviation, minimum, maximum) for serum folates, vitamin B12, vitamin B6 metabolites (pyridoxal and pyridoxal-5-phosphate), calcium, phosphorus, sodium, zinc, copper and iron, as well as blood hemoglobin and packed cell volume are reported for each studied time. Differences between parities and between each time are also reported. Results from the present report demonstrate that knowledge of the physiological state of the sows is critical for the assessment of nutritional status of an individual or a breeding herd by interpretation of analyses of blood constituents.

Animals↗

Sensitivity of reproducing sows and suckling pigs to stray voltage.

OBJECTIVE: To evaluate whether stray voltage reduces welfare of sows and their litters, causes reproductive problems, or impairs growth and survival of suckling pigs. ANIMALS: 120 gilts assigned randomly to 3 treatment groups: 2-V baseline plus 3-V pulses (2-5 V); 5-V baseline plus 3-V pulses (5-8 V); and control treatment (0-0 V). PROCEDURE: Behavior was recorded during gestation and lactation. Water and feed intakes were measured daily, milk composition was evaluated once during lactation, and hematocrit, hemoglobin, glucose, total protein, aspartate transaminase, alanine transaminase, albumin, globulins, and fatty acids values were measured at mating, weeks 8 and 15 of gestation, parturition, and weaning. Prolific ability of sows, mortality and disease of suckling pigs, and growth rate until 56 days of age were recorded. RESULTS: Gilts under voltage were lying down more often and performing less abnormal behaviors than were control gilts. Behavior of sows and suckling pigs was not affected by treatments. Water and feed intakes were similar among treatments, except during week 1 of lactation where feed intake was lower in the control group. Fecundity and prolific ability of sows, percentage of stillbirth, growth rate of suckling pigs, and milk composition were similar among treatments. More suckling pigs died in 2-5-V group than in other groups, but diarrhea was more frequent in the control group. Blood metabolites were similar among treatment groups. CONCLUSIONS: Transient stray voltage at values up to 8 V did not impair the welfare, reproductive performance, or health of sows and suckling pigs.

Animal Welfare↗

Fatal hepatotoxicity following oral administration of amiodarone.

OBJECTIVE: To report a case of fatal hepatotoxicity associated with the chronic use of oral amiodarone. CASE SUMMARY: Long-term administration of amiodarone for the control of intractable ventricular tachycardia was associated with fatal hepatotoxicity in a patient receiving amiodarone for 14 months. DISCUSSION: Although most hepatic adverse effects associated with amiodarone are transient and reversible with time, deaths resulting from amiodarone-induced hepatotoxicity have been reported. The relation of hepatotoxicity to cumulative dose and duration of therapy is debated. The histopathologic features of amiodarone-induced hepatotoxicity include Mallory bodies, steatosis, intralobular inflammatory infiltrates, fibrosis, and phospholipidosis. CONCLUSIONS: Evidence pertaining to both mild and severe amiodarone toxicity indicates that cumulative dose may correlate with overall toxicity and, therefore, maintenance doses should be kept as low as possible. Patients should be followed with monitoring of liver function test results every 3-6 months.

Administration, Oral↗

Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity.

Digoxin intoxication occurs frequently and may require treatment with digoxin-specific Fab therapy. Little is known, however, regarding the biological fate of this compound. Pharmacokinetic studies have not been performed in healthy volunteers, but there are limited kinetic data from patients who have received therapy for the treatment of digoxin toxicity. Digoxin-specific Fab is eliminated via renal and nonrenal routes, having a volume of distribution slightly exceeding extracellular volume (0.40 L/kg) and an elimination half-life of 16 to 20 hours. Patients with renal impairment and end-stage renal disease have elimination half-life values that are prolonged up to 10-fold in magnitude, while volume of distribution is unaffected. Systemic clearance of digoxin-specific Fab is approximately 0.32 ml/min/kg in digoxin-toxic patients with preserved renal function. Renal failure also decreases Fab clearance by up to 75%. Therefore, Fab may reside in the serum of anephric patients for 2 to 3 weeks after administration. More important is the effect of Fab on the disposition of digoxin. Because digoxin-specific Fab has a stronger digoxin-binding affinity than do biological membranes, it can sequester tissue-bound and intracellular digoxin into the extracellular spaces. This results in a rapid increase in digoxin serum concentrations in the central compartment. Since the majority of digoxin is bound by Fab, it cannot interact with its biological receptor and thus reverses digoxin toxicity. The pharmacokinetic fate of total digoxin after administration of digoxin-specific Fab follows that of Fab. However, it appears that the elimination half-life of Fab is slightly shorter than that of total digoxin in patients with end-stage renal disease, suggesting that the clearance of Fab is slightly faster than that of total digoxin. Free digoxin concentrations fall rapidly after Fab administration and then rebound upwards within 12 to 24 hours. This rebound in free digoxin concentrations, however, is delayed by 12 to 130 hours in patients with renal dysfunction and end-stage renal disease. Rebound in free digoxin concentrations occurs during the initial phase of the biexponential decline of the serum concentration-time profile for digoxin-specific Fab, suggesting that distribution from the vascular spaces is the likely cause. Following the increase, free digoxin concentrations decline in a manner that is dependent on renal and nonrenal routes of elimination. During this time period it is evident that Fab retains it capability of binding digoxin while it resides in plasma. There is no evidence to support a dissociation between the Fab-digoxin complex over extended periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modulatory effect of dexamethasone on ornithine decarboxylase activity and gene expression: a possible post-transcriptional regulation by a neutral metalloprotease.

The intracellular effect of dexamethasone (DXME) on the activity and gene expression of ornithine decarboxylase (ODC) was studied in Syrian hamster embryo cells (SHE). The ODC activity (expressed as nmoles decarboxylated ornithine mg-1 protein h-1) was 4.61 +/- 0.14 in untreated cells, whereas it increased to 14.38 +/- 0.26 after 5 h treatment with 1.6 x 10(-7) M TPA. In contrast, DXME (2.5 x 10(-5) M) reduced the ODC activity by 50 per cent to 2.35 +/- 0.22. In cells co-treated for 5 h with TPA and DXME, ODC activity decreased to the level of the untreated cells. However, when DXME was added 3 h after TPA treatment for 2 h, in the continuous presence of TPA, the ODC activity unexpectedly increased further to 16.44 +/- 1.05. The modulation of ODC activity correlated partly with the level of ODC mRNA. Thus when cells were treated with TPA, the ODC mRNA increased threefold, whereas it decreased by 30 per cent when the cells were exposed to DXME. In TPA-DXME co-treated cells, as in TPA pretreated cells followed by DXME for 2 h, a decrease (31.25 per cent and 12.5 per cent respectively) was observed in ODC mRNA. In turnover studies, DXME was found to increase the stability of ODC; the discrepancy between ODC activity and ODC mRNA levels could result from an inhibitory effect of the corticoid on proteolysis of ODC. Studies of lysosomal protease showed that the activities of cathepsins L, B and H decreased following TPA treatment. DXME also inhibited cathepsin L and B activities, but stimulated cathepsin H.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of bulky diets based on wheat bran or oat hulls on reproductive performance of sows during their first two parities.

The aim of the present study was to determine the effect of different degrees of bulkiness in the gestation diet on reproductive performance of sows during their first two parities. The density of the diets was modified by incorporating a high proportion of fibrous ingredients (wheat bran and corn cobs in Diet 2 and oat hulls and oats in Diet 3). A diet without fibrous ingredients was used as a control (corn and soybean meal in Diet 1). Although all the gestation diets were formulated to provide the same daily intake of the major nutrients, sows fed Diet 3 were the lightest and had the lowest backfat thickness (P < or = .05) during both parities, and those fed Diet 2 were the heaviest and the fattest (P < or = .05) during the second parity. These results seem to indicate an overestimation of the calculated nutritive value of Diet 3, whereas those obtained with Diet 2 seemed to be linked to its marked effect on behavior of sows during the second parity. There was no marked effect (P > .11) of treatments on the number of pigs born alive, on preweaning mortality, or on the weaning-to-estrus interval. At parturition, total litter weight was similar among treatments in the first parity, whereas in the second parity it was greater (P < or = .05) in sows fed Diet 2 than in those fed Diets 1 and 3. In both parities, feed intake of the common lactation diet given during lactation was 5% higher (P < or = .05) for sows fed Diet 3 during gestation than for sows fed the other diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Reconciling productivity and welfare in intensive pig husbandry: a challenge for the year 2000.

In the first part of this paper, the authors discuss the growing concern of consumers for farm animal welfare, and the attitude adopted by veterinarians to cope with this new and more humanitarian concept of intensive husbandry. The effects of intensification of pig production on the ability of pigs to adapt, and the behavioural, husbandry and health consequences of the principal stress factors in pig rearing are reviewed and illustrated by examples from recent research. In conclusion, the authors discuss the importance of constructive integration of welfare into pig production, in training courses and in actual application.

Animal Husbandry↗