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Biomedical subjects

L Singer

Publications and source records attributed to L Singer.

At least 19 recordsLinked to original sources

Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene.

The third component of complement (C3) is an important mediator of inflammation. Murine and human genomic cosmid clones were isolated, characterized and sequenced 5' to the complement C3 gene transcriptional initiation sites to determine cis elements that participate in constitutive and regulated C3 gene expression. The murine and human 5' flanking regions are 51% identical overall, with positions -36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but deletion and transfection analysis using reporter gene constructs in HepG2 cells indicated that only the TATA element at position -30, together with sequences -395 to -111, are essential for constitutive expression of murine C3 in hepatocytes. Deletion analysis also suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Sequences between -90 to -41 confer both enhancer activity and interleukin-1/-6 (IL-1/IL-6)-responsiveness. Mutation analyses showed that both sequences between -88 and -83 and -77 to -72 are essential for enhancer activity and responsiveness to IL-1, but only sequences between -88 and -83 are necessary for IL-6-responsiveness. A gel-retardation assay showed that several nucleoproteins, perhaps of the C/EBP family, from HepG2 cells bound to sequences between -88 to -83. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene expression and provide evidence for specific transacting factors.

Animals

Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers.

To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word-completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems.

Adult

Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers.

The effects of two benzodiazepines, diazepam (15 or 20 mg orally) and lorazepam (1.75 or 2.5 mg orally), and a placebo on explicit memory, lexical priming and perceptual priming were assessed using a free-recall, a word-completion and a picture-completion test. The picture-completion test included two different study conditions intended to manipulate the magnitude of the priming effect. Sixty healthy volunteers took part in this double-blind study. Free-recall performances were altered by both drugs. Lorazepam impaired word-completion and picture-completion performance, whereas diazepam only exhibited a deleterious effect on the more sensitive of the two measures of the picture-completion test. These results indicate that the two benzodiazepines have differential amnestic effects. It is suggested that these differential effects could be accounted for by a different cortical distribution of the two benzodiazepines.

Adult

Childhood medical and behavioral consequences of maternal cocaine use.

Reviewed available studies of the impact of fetal cocaine exposure on child medical and developmental outcome, as well as the current status of clinical psychological interventions and research strategies. Current studies are inconclusive but suggest that prenatal exposure to crack-cocaine can have significant effects on the growth and neurological development of the infant, with the potential of later learning and behavioral disabilities. Social-environmental correlates of maternal cocaine use are confounding factors with known negative effects on child outcome. Large, population-based studies using multivariate analyses are needed to determine the independent effects of cocaine on child outcome relative to other confounding variables.

Child, Preschool

Pediatric management of Robin sequence.

The care of infants with Robin sequence is discussed with special reference to upper airway obstruction and feeding difficulties. The use of nasopharyngeal tubes is recommended initially to alleviate the immediate consequences of hypoxia. Modifications in feeding procedures are minor and involve enlarging the hole in the nipple and keeping the nipple and infant positioned appropriately.

Airway Obstruction

Upper airway obstruction and the Robin sequence.

Both the etiology of Robin sequence and the mechanisms of upper airway obstruction are heterogeneous. As a result, generalizations about the care of newborns with the combination of micrognathia, cleft palate, and airway obstruction cannot be made. Management of the airway obstruction should be based on the results of direct endoscopic observation of the site of obstruction and not on the presumptive diagnosis of glossoptosis. It should not be assumed that "catch-up growth" of the mandible will occur and lead to spontaneous resolution of either the airway obstruction or the micrognathia. The presentation of the child with Pierre Robin sequence should not be the end of the diagnostic search, but rather the beginning.

Airway Obstruction

Pharyngeal flap surgery: postoperative complications.

Using a protocol specifically designed to decrease the risk factors for postoperative morbidity and upper airway obstruction, we have essentially eliminated major complications after pharyngeal flap surgery while maintaining excellent speech results. The protocol includes inserting a short pharyngeal flap into a tissue "sandwich" and keeping an NP tube in place for 48 hours postoperatively. The complications reduced by use of this protocol include apnea and other upper respiratory complications, as well as bleeding. In addition, postoperative discomfort is decreased with the current protocol. Using this approach, pharyngeal flap surgery is highly effective in improving speech and is associated with low morbidity.

Adolescent

Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge.

Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight

Explicit memory and repetition priming in depression. Preliminary findings.

Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia.

Dementia

Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period.

The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease in food intake and body weight of marmots. When infused with insulin into their lateral ventricles (Alzet #2002 minipumps), animals had significantly lower food intake as compared to their food intake during the control period. In addition, these animals lost body weight during the period of the insulin infusion. We suggest that during the summer when marmots are not hibernating and are actively feeding, brain insulin levels may play a role in regulating food intake.

Adipose Tissue

Seasonal changes in CSF insulin levels in marmots: insulin may not be a satiety signal for fasting in winter.

Plasma insulin (PI) reportedly crosses the blood-brain barrier in mammals and acts with the central nervous system (CNS) to reduce food intake. Animals that hibernate (hibernators) eat little or no food from early winter (November) to spring (April). This lack of food intake may be due to elevated PI concentrations acting within the CNS. In this study, we determined whether hibernators have altered insulin levels within the CNS at different times during the circannual cycle of metabolism and feeding. Plasma and cerebrospinal fluid (CSF) immunoreactive insulin concentrations were measured in marmots (Marmota flaviventris) during the feeding phase of the body weight cycle and during the fasting period (hibernation). Basal plasma and CSF samples were collected in September, November, January, and April. In addition, plasma and CSF insulin levels were monitored during a 2-h intravenous infusion of glucose (20% wt/vol) that stimulated pancreatic B-cell production of insulin. During the spring feeding period, we found that as PI levels rise, so do CSF insulin concentrations. However, in fall and winter when marmots are fasting, very little insulin entered the CSF even when PI levels were significantly elevated. Furthermore, the longer the fast, the lower was the CSF insulin under both basal and infusion conditions. These results lead us to conclude that elevated CSF insulin is not a likely cause of suppressed food intake in fasting marmots.

Animals

Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride.

We have examined the possible effect of fluoride intake on chromosome damage. There was no evidence of increased frequency of chromosomal aberration in bone marrow or testis cells of mice with either 50 ppm fluoride intake over several generations or 100 ppm intake for 6 weeks compared to animals drinking distilled water. Fluoride was not found to be mutagenic in a widely used bacterial mutagenesis assay over a range of 0.1 to as high as 2000 microgram fluoride per plate.

Animals

Lack of effect of fluoride on urinary cAMP excretion in rats.

The urinary excretion of cyclic 3'5'-adenosine monophosphate (cAMP) was measured in rats provided a low fluoride diet (less than 0.5 ppm) and drinking water containing either 0 or 25 ppm of fluoride. The pMole cAMP/microgram creatinine ratio decreased with age but was not influenced by fluoride intake.

Animals

[Lithium and thyroid function. Significance of the TRH test in the diagnosis of lithium-induced thyroid dysfunction].

The treatment by lithium is known to involve certain endocrine complications. Those concerning the thyroid function, with risk of a frank hypothyroidy, are the most important. Aiming to appreciate the frequence and the intensivity of the endocrine effects of lithium, the thyroid parameters and the steady state of the hypothalamo-pituitary-thyroid axis were tested using the TRH test in 52 patients with maniaco-depressive psychosis with special attention to TSH, prolactin and growth hormone: 24 out of them were treated for 1 month to 6 years by lithium; the 28 others were considered as controls. The lithium treatment involves a decrease in the free thyroxine index (1.78 +/- 0.09 vs 2.16 +/- 0.09; p less than 0.01), an increase in the mean baseline TSH level (5.80 +/- 1.49 vs 2.70 +/- 0.24 microU/ml; p less than 0.05) and a noteworthy increase in the TSH responsiveness to TRH (22.7 +/- 2.14 vs 9.75 +/- 1.63 microU/ml; p less than 0.005). The TSH supranormal responses were neither correlated with the length of the treatment nor with the age of the patients. They appear as the consequence of a decrease in the thyroidal hormone secretion. The basal and stimulated prolactinemias remain comparable in the two groups of patients and no response of growth hormone occured after TRH. The TRH test must be considered as a useful complement for the surveillance of the patients treated with lithium because it permits to diagnose early the lithio-induced thyroid dysfunction.

Adolescent

Concentrations of ionic, total, and bound fluoride in plasma.

We found no significant difference between the means for ionic, bound, and total fluoride concentrations in the plasma of male and female subjects of the same age, living in a community with fluoridated water. When results for the 264 fasting subjects were therefore combined according to age, they indicated that persons over 60 years of age have a significantly higher mean ionic (3.89 mumol/L) and total (6.58 mumol/L) fluoride concentration in plasma than do younger age groups. For younger age groups, means ranged from 2.74 to 3.05 mumol/L for ionic fluoride and from 4.74 to 5.58 mumol/L for total. The bound fluoride concentration was lower in individuals 21 to 30 years of age (1.89 mumol/L) than in older age groups (for whom means ranged from 2.42 to 2.68 mumol/L), but was not significantly different from that of individuals who were younger (2.21 mumol/L). A tendency for the mean ionic fluoride concentration to increase with age was noted, but the concentration was significantly higher than the preceding decade group only in those persons over 60 years of age.

Adolescent