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Biomedical subjects

L Singer

Publications and source records attributed to L Singer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Umbilical cord fluoride serum levels may not reflect fetal fluoride status.

OBJECTIVE: To evaluate the reliability of fluoride levels in the umbilical cord as reflecting neonate fluoride status. DESIGN: Prospective study of fluoride levels of pregnant women at term and their neonates. SETTING: Delivery room and maternity unite of Hadassah Hospital Mount Scopus. PATIENTS: Fluoride serum levels were determined in the sera of 20 women with normal pregnancies at term, during delivery, in the corresponding mixed cord sera and neonatal sera at 24 hours after delivery. RESULTS: The mean maternal fluoride serum level was 0.0303 microgram/ml (SD 9.015), mean cord fluoride serum level 0.0183 microgram/ml (SD 0.012), and mean neonatal fluoride serum 0.0380 microgram/ml (SD 0.016). CONCLUSION: The significantly (p < 0.001) low mixed cord serum levels of fluoride as compared with neonatal and maternal serum levels may be explained by placental sequestration of fluoride. It is suggested that cord serum fluoride levels to not reflect fetal fluoride status.

Female↗
PubMed1994

Inherited human complement C3 deficiency. An amino acid substitution in the beta-chain (ASP549 to ASN) impairs C3 secretion.

We recently described a case of hereditary complement C3 deficiency (C3D) in a New Zealand male who has a small amount of serum C3 (7 micrograms/ml), a normal size 5.2-kilobase C3 mRNA that is present in normal quantities, and a normal size M(r) 180,000 proC3 molecule that is synthesized in normal amounts. Secretion of C3 from this patient's cells was greatly diminished, however, and an aberrant C3 trypsin cleavage profile indicated an abnormality in the proC3 structure. To determine the primary structure of the C3D proC3 molecule, the corresponding cDNA was cloned and sequenced in the present study, revealing a normal signal peptide, tetraarginine linker, and thiolester domain. One nucleotide substitution in exon 13 (G1705 AC to AAC) was found, however, that resulted in an amino acid change in a highly conserved region of the C3 beta-chain (Asp549 to Asn). This substitution has not been described in any individual with either C3 Fast or C3 Slow phenotypes. Immunoprecipitation of C3 from L-cells transfected with full-length normal and C3D cDNAs demonstrated that C3 was secreted by the cells transfected with the normal C3 cDNA; however, only a C3 precursor was detected in the intracellular compartment of the cells transfected with the C3D cDNA and none detected extracellularly. Immunofluorescence studies revealed a perinuclear localization of C3 in the C3D transfectants, arrested early in the secretory pathway. Allele-specific polymerase chain reaction analysis demonstrated that this New Zealand family is a compound heterozygous C3D kindred, with the Asn549 point mutation being inherited from the mother and a yet undescribed C3 defect being inherited from the father. Taken together, these data indicate that 1) C3 deficiency is caused in a New Zealand kindred by two distinct molecular genetic mutations, one being an amino acid substitution in a highly conserved region of the beta-chain that results in impaired C3 secretion, and 2) the molecular basis of this deficiency has not been described in any other C3-deficient individual, providing additional evidence that multiple defects cause inherited C3 deficiency in humans.

Alleles↗
PubMed1994

Problems in postoperative management after anterior cricoid split.

OBJECTIVE: Describe complications and postoperative management problems associated with the anterior cricoid split. DESIGN: Retrospective case series. SETTING: Urban referral hospital. PATIENTS: Nine consecutive patients with acquired subglottic stenosis believed amenable to the anterior cricoid split. INTERVENTION: The anterior cricoid split was performed on 10 occasions between June 1989 and June 1992. MAIN OUTCOME MEASURE: Extubation or decannulation. RESULTS: Six of nine patients underwent decannulation, with success. Management problems included those related to surgery or postoperative endotracheal stenting, preexisting medical conditions, and postoperative sedation requirement. CONCLUSIONS: The number of postoperative complications and management problems was highest in those patients with both bronchopulmonary dysplasia and preexisting tracheotomy.

Bacterial Infections↗
PubMed1994

Direct and indirect interactions of cocaine with childbirth outcomes.

OBJECTIVE: To evaluate neonatal sequelae of maternal cocaine use during pregnancy. METHODS: One hundred women positive for cocaine use during pregnancy were compared with 100 matched controls who did not use cocaine. Maternal characteristics and infant neonatal outcomes were compared. We used t tests, chi 2, and multiple regression analyses to evaluate the contributions of cocaine vs other drugs to outcome. RESULTS: Cocaine was the best predictor of increased incidence of abortions, higher maternal gravidity, and poorer prenatal care. Cocaine was also the best predictor of preterm birth and of lower birth weight, after controlling for prematurity. Maternal use of cocaine and alcohol in combination was the best predictor of decreased linear growth, after controlling for prematurity. CONCLUSIONS: Maternal cocaine use predicts negative birth outcomes directly, as well as through obstetric risk factors of abortion history and less prenatal care. Interactive effects of cocaine and alcohol should be considered in future studies of birth outcomes.

Abortion, Spontaneous↗
PubMed1994

Inherited complement C3 deficiency: a defect in C3 secretion.

The molecular basis of inherited complement C3 deficiency in a 20-year-old newly diagnosed male patient was studied. Using an enzyme-linked immunosorbent assay, the patient's C3 serum level was found to be approximately 7 micrograms/ml, which is less than 1% of normal. In contrast, Northern analysis indicated that the patient's C3 mRNA was of normal size and quantity. Peripheral blood monocytes (PBM) and skin fibroblast cultures (F) from the patient and from healthy donors were labeled for 2 h with [35S] methionine. Analysis of cell lysates and supernatants by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated normal levels of C3 in lysates of patient's PBM and F. However, C3 secretion in the patient's cells was extremely reduced, with pulse-chase experiments demonstrating a long delay in the disappearance of intracellular C3. Secretion of C1r and factor B by the patient's cells was normal. Lipopolysaccharide and interleukin-1 increased C3 synthesis in the patient's PBM and F, but had no effect on the secretion. SDS-PAGE analysis of trypsin-cleaved intracellular C3 revealed an aberrant cleavage profile for the patient's C3. Collectively, these data indicate that C3 deficiency in this patient is due to a defect in the C3 secretion, probably as the result of abnormality in the proC3 structure.

Adolescent↗
PubMed1994

Eating behaviour and depression before and after antidepressant treatment: a prospective, naturalistic study.

Eating behaviour of severely depressed patients was assessed before (n = 56), after acute (n = 46) and during maintenance (n = 35) treatment and compared to matched normal controls in order to investigate the behavioural mechanisms underlying the weight gain induced by antidepressants. Assessments included food intake, appetite and food preferences. Before treatment, there was a decrease in appetite and in food intake with a relative excess of carbohydrates and a preference for sweets. Maintenance treatment was associated with substantial weight gain. All differences in eating behaviour between patients and controls disappeared, with the exception of a decrease in appetite in a subgroup of less-improved patients. These results suggest that antidepressant treatment induces weight gain by mechanisms that are largely independent of their action on mood.

Adult↗
PubMed1994

Explicit memory, repetition priming and cognitive skill learning in schizophrenia.

Explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, were examined in twenty-four schizophrenic patients and twenty-four normal control subjects previously matched for sex, age, and educational level. Two explicit tasks, free recall and frequency monitoring, and two implicit tasks, word completion and the Tower of Toronto puzzle, a variant of the Tower of Hanoi puzzle, were selected. The performance of schizophrenic patients was impaired in both explicit tasks, whereas repetition priming was intact; in the Tower of Toronto puzzle, a deficit was observed in problem solving, but not in skill learning. This dissociation between explicit and implicit memory is not entirely consistent with the hypothesis of a deficiency in effort-demanding information processing. It could be better accommodated by a model of a disturbance in the internal representation of context.

Adolescent↗
PubMed1994

Complement C3 deficiency: human, animal, and experimental models.

The third complement component (C3) is a multifunctional glycoprotein that interacts with numerous serum proteins, cell surface receptors, and membrane-associated regulatory proteins. Deficiencies of C3 have been reported in several human kindred of different ethnic backgrounds and from different geographic regions. In addition, inherited C3 deficiency has been discovered in certain strains of guinea pigs, dogs, and rabbits, and has been experimentally induced in animals by injections of cobra venom factor. Studies of the C3-deficient humans and animals have demonstrated the important roles performed by C3 in the immune response, opsonization and phagocytosis of pathogens, and immune complex solubilization. Current knowledge of the molecular and cellular basis of complement C3 deficiency indicates that C3 deficiency is caused by numerous molecular genetic mutations that include splicing defects, a partial gene deletion, and a critical amino acid substitution. With the advent of gene ablation technology, C3-deficient murine models can now be established, making it possible to examine the role that C3 plays in the molecular pathogenesis of many different diseases.

Animals↗
PubMed1994

A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds.

To determine the molecular defect accounting for the deficiency of pulmonary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequence of the SP-B transcript in affected infants was ascertained. A frameshift mutation consisting of a substitution of GAA for C in codon 121 of the SP-B cDNA was identified. The three affected infants in the index family were homozygous for this mutation, which segregated in a fashion consistent with autosomal recessive inheritance of disease. The same mutation was found in two other unrelated infants who died from alveolar proteinosis, one of whom was also homozygous, and in the parents of an additional unrelated, affected infant, but was not observed in 50 control subjects. We conclude that this mutation is responsible for SP-B deficiency and neonatal alveolar proteinosis in multiple families and speculate that the disorder is more common than was recognized previously.

Amino Acid Sequence↗
PubMed1993

Neurodevelopmental effects of cocaine.

How and to what extent fetal cocaine exposure produces specific, negative, long-term effects on infant neurodevelopmental competence has not yet been determined. We have argued previously that results from animal studies, the findings of intrauterine growth retardation in human studies, and the markedly higher incidence of numerous associated risk factors in cocaine-exposed cohorts herald significant clinical risk to the developing infant. Recognition of infant risk status should not imply condemnation of a group of children but, as with preterm infants, lead to aggressive, national, social, and scientific efforts to delineate and intervene with potential sequelae of drug exposure.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗