Biomedical subjects

D F Smith

Publications and source records attributed to D F Smith.

At least 163 records · Page 9Linked to original sources

PubMed1991

Decreased biosynthesis of Forssman glycolipid after retinoic acid-induced differentiation of mouse F9 teratocarcinoma cells. Lectin-affinity chromatography of the glycolipid-derived oligosaccharide.

Glycolipids synthesized by the mouse teratocarcinoma F9 cells and F9 cells (RA/F9 cells) induced to differentiate by a 3-day treatment with 0.1 microM all-trans-retinoic acid were analyzed. Both F9 cells and RA/F9 cells were incubated in media containing either D-[6-3H]galactose or D-[6-3H]glucosamine; the metabolically-radiolabeled glycolipids were isolated and the oligosaccharides were released from the glycolipids by ozonolysis and alkali fragmentation. From both cells, a single major pentasaccharide was isolated from the mixture of neutral [3H]oligosaccharides by affinity chromatography on a column of immobilized Helix pomatia agglutinin. The structure of this oligosaccharide was analyzed by methylation analysis and specific exoglycosidase treatments and identified as the Forssman pentasaccharide alpha-D-GalpNAc-(1----3)-beta-D-GalpNAc-(1----4)-alpha-D-Galp-(1----4)-b eta-D- Galp-(1----4)-D-Glc. There was a 3-4-fold decreased amount of the Forssman pentasaccharide from RA/F9 cells relative to F9 cells. In contrast, there were no major differences between these cells in the levels of globoside, the precursor to Forssman glycolipid. To investigate the basis for the decline in Forssman glycolipid synthesis upon differentiation, the activity of UDP-D-Gal-NAc:GbOse4Cer alpha-(1----3)-N-acetyl-D-galactosaminyltransferase (Forssman synthase) was determined in extracts of both the F9 and RA/F9 cells. The specific activity of Forssman synthase was approximately 70% lower in differentiated relative to the nondifferentiated cells. These data demonstrated that F9 cells synthesize authentic Forssman glycolipid, and that its expression and the activity of Forssman synthase were decreased following induced cellular differentiation.

Animals↗

PubMed1991

Fetal alcohol syndrome in adolescents and adults.

Fetal alcohol syndrome is a specific recognizable pattern of malformation. Manifestations in 61 adolescents and adults suffering from alcohol teratogenesis are presented. After puberty, the faces of patients with fetal alcohol syndrome or fetal alcohol effects were not as distinctive. Patients tended to remain short and microcephalic, although their weight was somewhat closer to the mean. The average IQ was 68, but the range of IQ scores widely varied. Average academic functioning was at the second- to fourth-grade levels, with arithmetic deficits most characteristic. Maladaptive behaviors such as poor judgment, distractibility, and difficulty perceiving social cues were common. Family environments were remarkably unstable. Fetal alcohol syndrome is not just a childhood disorder; there is a predictable long-term progression of the disorder into adulthood, in which maladaptive behaviors present the greatest challenge to management.

Adaptation, Psychological↗

PubMed1991

[Sex differences among Danish physicians of type A personality].

The Jenkins Activity Survey was used for measuring four components of coronary-prone behaviors (i.e. Factors A, S, H, and J) in a large random sample of male and female physicians as well as in a large random sample of males and females in the general public. As expected, males in the general public tended to score higher than females in terms of coronary-prone behavior. In contrast, female physicians scored higher than male physicians on several components of coronary-prone behavior related to career goals, ambitiousness, job involvement, and time urgency. The findings suggest that female physicians in Denmark may be influenced by factors that make them particularly prone to the development and/or expression of coronary-prone behaviors.

Adult↗

PubMed1991

Effects of pyrroloisoquinoline enantiomers ((+)- and (-)-McN-5652-Z) on behavioral and pharmacological serotonergic mechanisms in rats.

A behavioral syndrome consisting of 5-hydroxytryptamine (5-HT)-dependent behaviors (e.g. forepaw treading, retropulsion and splayed hindlimbs) as well as hyperthermia occurred after bilateral injection of the (6S, 10bR)-(+)-enantiomer of McN-5652-Z into the cerebral ventricles in pargyline-treated rats. Both the behavioral syndrome and hyperthermia produced by (+)-McN-5652-Z were counteracted by parachlorophenylalanine or ketanserin. The (6R, 10bS)-(-)-enantiomer of McN-5652-Z influenced neither behavior nor body temperature. The enantiomers of McN-5652-Z differed also in their ability to inhibit ex vivo binding of paroxetine in rat frontal cortex and hypothalamus, in vitro uptake of 5-HT in rat blood platelets, and 5-HT-induced contraction of rat vascular smooth muscle, with (+)-McN-5652-Z being most active. No difference was observed between the effects of (+)- and (-)-McN-5652-Z on 5-HT metabolism by rat brain monoamine oxidase. Molecular models of N-protonated enantiomers having a cis B,C-ring juncture and a B-ring chair conformation were differentiated using a hypothetical model of the 5-HT uptake area. The findings indicate that the enantiomers of McN-5652-Z are useful tools for studying the stereoselectivity of behavioral and pharmacological effects exerted by serotonergic neurotransmission.

Animals↗

PubMed1991

Right displacement of the abomasum and abomasal volvulus in dairy cows: 458 cases (1980-1987).

Clinical and surgical findings in 458 dairy cows with right displacement of the abomasum or abomasal volvulus (AV) were analyzed to determine the association between these variables and the outcome (productive, salvaged, or terminal) of the affected cow. Heart rate at initial examination was higher in the salvaged and terminal groups of cows (P less than 0.0001) than in the productive group. The plasma Na+ concentration was lower in the salvaged and terminal groups of cows (P less than 0.0001) than in the productive group. The plasma C1- concentration was lower in the salvaged group of cows than in cows with either productive or terminal outcomes (P less than 0.0001). Anion gap was significantly higher (P less than 0.0001) in the salvaged and terminal groups than in cows classified as productive. On the basis of surgical findings, cattle with right displacement of the abomasum were more likely to survive than cows with AV. Cows that required fluid decompression of the abomasum via abomasotomy were less likely to survive than those in which gaseous decompression was performed. Cows with evidence of vascular compromise of the abomasal wall were less likely to survive than those with normal abomasal serosa. Preoperative heart rate and anion gap had positive correlations with the presence of abomasal necrosis, whereas temperature, venous blood pH, plasma bicarbonate, and base excess concentrations had negative correlations. Cows in terminal stages of AV were likely to have a mixed primary acid-base disturbance, consisting of metabolic alkalosis with superimposed metabolic acidosis. These findings were highly correlated with abomasal necrosis.

Abomasum↗

PubMed1991

The major serum protein of Drosophila larvae, larval serum protein 1, is dispensable.

Null alleles of all three genes (alpha, beta and gamma) coding for the major serum protein of Drosophila larvae, larval serum protein 1, have been characterized at the protein level and by analysis of their RNA and DNA. Each allele completely lacks one polypeptide chain. beta shows an unaltered gene but reduced levels of RNA, alpha shows restriction-fragment-length polymorphism and shows low levels of transcript, while gamma is a deletion. The three null alleles have been combined to give a strain without the gene for larval serum protein 1 which survives.

Alleles↗

PubMed1991

Beta-haemolytic non-group A streptococci and pharyngitis: a case-control study.

A case-control study was conducted to examine the association of beta-haemolytic non-group A streptococci and pharyngitis in a paediatric population (n = 502). No association could be found between disease and traditional Lancefield groups B, C, F, or G. When the analysis included the clustering of genetically related subgroups from different Lancefield groups, an association was evident for moderate and heavy quantitations of beta-haemolytic "large colony" group C and G streptococci (Streptococcus equisimilis and human biotypes of large colony group G streptococci) (p = 0.021). This study further defines a subset of the beta-haemolytic non-group A streptococci that merit recognition by both the laboratory and physician.

Case-Control Studies↗

PubMed1991

A microplate assay for analysis of solution-phase glycosyltransferase reactions: determination of kinetic constants.

We have developed a sensitive and simple method for assaying glycosyltransferase activities. This method makes use of solution-phase transferase reactions followed by capture to a microplate well coated with a substrate-specific monoclonal antibody. Sugar incorporation is quantitated by binding a saccharide-specific lectin and using bioluminescent aequorin for a reporter molecule. We demonstrate this method using the glycoprotein hormone-specific GalNAc-transferase and its acceptor substrate, agalacto-hCG. As little as 20 ng of agalacto-hCG with 32 nU of GalNAc-transferase gives a detectable signal with less than 10% of the acceptor sites substituted. In addition to this high sensitivity, by doing the transferase reactions in solution, we can assay up to 10 micrograms of agalacto-hCG. We show that this allows the determination of Km and Vmax kinetic constants that compare well to those obtained with radiolabeled nucleotide sugars.

Aequorin↗

PubMed1991

A solid-phase assay for beta-1,4-galactosyltransferase activity in human serum using recombinant aequorin.

We have developed a sensitive and rapid solid-phase assay for the serum enzyme UDPGal:beta-D-GlcNAc beta-1,4-galactosyltransferase (beta 1,4-GT) (EC 2.4.1.38) that employs the recombinant bioluminescent protein aequorin as the enzyme label for product detection. The substrate for beta 1,4-GT is a neoglycoprotein, bovine serum albumin containing covalently attached GlcNAc residues (GlcNAc-BSA), and it was immobilized by adsorption in microtiter plate wells. Serum samples were added to each well along with saturating levels of UDPGal and Mn2+. Galactosylation of the neoglycoprotein acceptor by the serum beta 1,4-GT produces the N-acetyllactosamine derivative Gal beta 1, 4GlcNAc-BSA. The product formed is quantified by adding the biotinylated plant lectin Ricinus communis agglutinin-I, which binds specifically to N-acetyllactosamine, followed by the addition of streptavidin and the biotinylated aequorin. Aequorin produces a flash of light in response to Ca2+ and is detectable to 10(-19) mol in a luminometer. Using this assay, the beta 1,4-GT activity in human serum and the activity of a semipurified beta 1,4-GT are linear with time and serum concentration over a wide range. The reaction is dependent on UDPGal and Mn2+, is highly reproducible with a low background, and can be performed in a few hours. Assays employing aequorin have a wider range of linearity than those employing horseradish peroxidase as an enzyme label. These results demonstrate that the assay for beta 1,4-GT is useful for determining activity in heterogeneous samples and also demonstrate the utility of the recombinant protein aequorin for solid-phase assay methods.

Acetylglucosamine↗

PubMed1991

Seizure frequency, patient-perceived seizure severity and the psychosocial consequences of intractable epilepsy.

It is generally recognised that the assessment of treatment effects in epilepsy using seizure frequency as the only outcome measure may lack sensitivity. A patient-based seizure severity scale has been developed and initial results confirm its reliability and validity. As part of the further development of this scale it is important to explore the relationship between seizure severity, seizure frequency and the psychosocial consequences of intractable epilepsy. One hundred patients with medically refractory partial seizures completed a quality of life questionnaire including measures of physical (seizure severity and frequency), social and psychological well-being (anxiety, depression, self-esteem, locus of control and happiness). Multivariate analysis demonstrated that individual psychological variables were best predicted by other psychological variables. However, when these were removed from analysis, seizure severity was the most significant predictor of self-esteem (P = 0.005), locus of control P = 0.039) and anxiety (P = 0.048). Seizure frequency did not contribute significantly to the variance of any of the psychological factors. These results highlight the importance of considering seizure severity when assessing treatment effects in epilepsy and provide further evidence for the construct validity of a novel patient-based seizure severity scale.

Activities of Daily Living↗

PubMed1991

The development of a seizure severity scale as an outcome measure in epilepsy.

In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post-ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid.

Adolescent↗

PubMed1991

Postoperative course after sufentanil or fentanyl anesthesia for coronary artery surgery.

Postoperative hemodynamic effects were compared in 50 patients randomly selected to receive either sufentanil, 25 micrograms/kg, or fentanyl, 100 micrograms/kg, anesthesia for coronary artery bypass grafting. The two groups exhibited similar patient demographics; dose of premedicants and muscle relaxants; and use of inhalation agents. Values for 15 hemodynamic variables were recorded at baseline and at six postoperative times. The times to awakening, response to verbal commands, and extubation were also noted. Patients who received sufentanil had a more stable course, with higher cardiac outputs, lower systemic vascular resistances, and a lower incidence of hypertension. Postoperatively, the two groups had similar values for time to awakening, response to verbal commands, and extubation. Elimination half-lives differed significantly: 554 +/- 91 minutes (fentanyl) versus 277 +/- 60 minutes (sufentanil). Serum concentrations of both decreased linearly. The added advantages of postoperative hemodynamic stability could be important in the choice of anesthetic.

Anesthesia Recovery Period↗

PubMed1991

The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.

Granule membrane protein-140 (GMP-140) is an inducible receptor for myeloid leukocytes on activated platelets and endothelium. Like other selectins, GMP-140 recognizes specific oligosaccharide ligands. However, prior data on the nature of these ligands are contradictory. We investigated the structural features required for ligand interaction with GMP-140 using purified GMP-140, cells naturally expressing specific oligosaccharides, and cells expressing cloned glycosyltransferases. Like the related selectin endothelial leukocyte adhesion molecule-1 (ELAM-1), GMP-140 recognizes alpha(2-3)sialylated, alpha(1-3)fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells, including the sequence Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNac beta-R (sialyl Lewis x). Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140. Although sialyl Lewis x is expressed by both myeloid HL-60 cells and CHO cells transfected with an alpha 1-3/4 fucosyltransferase, GMP-140 binds with significantly higher affinity to HL-60 cells. Thus, the sialyl Lewis x tetrasaccharide may require additional structural modifications or specific presentations in order for leukocytes in flowing blood to interact rapidly and with high affinity to GMP-140 on activated platelets or endothelium.

Amino Sugars↗

PubMed1991

A test-retest study of intelligence in patients with fetal alcohol syndrome: implications for care.

Successive IQ scores of 40 patients with fetal alcohol syndrome or possible fetal alcohol effects were compared to examine stability of IQ into mid-adolescence. There were no significant differences in IQ scores across time for patients with fetal alcohol syndrome and fetal alcohol effects. Group means and individual IQ scores remained stable over the average test-retest interval of 8 years. These data demonstrate the long-term enduring consequences of prenatal brain damage in the fetal alcohol syndrome, an entirely preventable developmental disability.

Adolescent↗

PubMed1991

The prognosis of primary intracerebral tumours presenting with epilepsy: the outcome of medical and surgical management.

It is not known whether conservative or early aggressive (resective surgery with or without radiotherapy) management is better for tumours presenting with epilepsy. The prognosis of 560 patients with a clinical and CT diagnosis of intrinsic supratentorial tumour was examined retrospectively. Epilepsy was the first symptom in 164 patients. Histological confirmation of diagnosis was available in 391 (70%) of cases. Median survival was 37 months in the group presenting with epilepsy and six months in those presenting with other symptoms (p less than 0.0001). Patients presenting with epilepsy were more likely to have a normal clinical examination, a non-enhancing low density lesion on CT scan and a low grade tumour. From Cox's stepwise proportional hazards model, significant independent variables adversely affecting prognosis were increasing age, focal neurological signs and enhancing CT lesions at diagnosis, non-resective surgery and male sex. Of those presenting with epilepsy 80 patients had surgical treatment within two months of CT diagnosis. The Cox's model failed to identify any beneficial effects for either early resective surgery or radiotherapy. In primary intracerebral tumours with presentations other than epilepsy, resective surgery and radiotherapy were amongst the important factors associated with prolonged survival. Primary intracerebral tumours presenting with epilepsy are relatively benign and their outcome appears to be chiefly determined by clinical factors.

Adolescent↗

PubMed1991

Group G streptococcal bacteraemia--a review of thirteen cases in Grampian.

Thirteen cases of group G streptococcal bacteraemia are described. All subjects were hospital in-patients between 1980-1988, and were either middle-aged or elderly. A primary site of infection was identified in 11, of whom nine had soft tissue infection and two had infections derived from the gut/biliary tree. Seven patients had underlying disease, two of whom had malignancy. One patient died of septicaemia. In the majority of patients early institution of treatment led to prompt recovery.

Aged↗

PubMed1991

A follow-up study of the community near the McColl waste disposal site.

To assess the effect of interim clean-up measures on the current health of a community, we conducted a follow-up survey of 193 residents living near the McColl waste disposal site and a comparison area located approximately 5 miles from the site. Results from this survey were compared with results from a similar survey conducted 7 years earlier. Odors were detected at least once per week by 32.7% of "high-exposed" respondents in 1988 compared with 68.5% in 1981, but prevalence odds ratios (PORs) comparing symptom reporting between "high-exposed" and comparison-area respondents were greater than that of the 1981 survey for 89% of symptoms. PORs comparing symptom reporting between these two areas were greater than 2.0 for 64% of symptoms assessed in the current survey. Symptoms reported in excess did not represent a single organ system or suggest a mechanism of response. PORs comparing respondents who were very worried about the environment and those reporting no worry were greater than 2.0 for 86% of symptoms. These finding, along with environmental data from the area, suggest that living near the waste disposal site and being very worried about the environment, rather than a toxicologic effect of chemical from the site, explain excess symptom reporting found in this follow-up study.

Adult↗

PubMed1991

Retrotransposons and evolution in phlebotomines.

The polymerase chain reaction was used to amplify a segment of the reverse transcriptase (RT) gene of putative retrotransposons from Phlebotomus (Larroussius) perniciosus, P. (L.) perfiliewi, P. (Phlebotomus) papatasi and Lutzomyia (Lutzomyia) longipalpis. Based on amino acid sequence comparisons with known RT genes, the amplified products of these species were shown to be derived from non-LTR retrotransposons related to the F element of Drosophila melanogaster. The usefulness of this technique is discussed in relation to taxonomy and genetic manipulation.

Amino Acid Sequence↗