Biomedical subjects

S Finley

Publications and source records attributed to S Finley.

10 recordsLinked to original sources

PubMed1991

Enhanced stability of subtilisin by three point mutations.

This study was undertaken to characterize the effect of three point mutations made on aprA-subtilisin on the stability of the protein to both heat- and detergent-induced denaturation. Asparagine residues at positions 109 and 218 were replaced with serine residues to prevent the possible cyclization between these asparagines and the adjacent glycine residues and hence to increase the long-term stability. The effect of these substitutions on conformational stability was examined by thermal denaturation. At high calcium concentrations, the Ser109-substituted analog showed a 3 degrees C higher transition temperature than that of aprA-subtilisin, while the Ser218 substituted analog had a 4 degrees C higher transition temperature. The analog with both changes had a 7 degrees C higher transition temperature than that of the original aprA-subtilisin, indicating that the contributions of the individual mutations were additive. The analog with both mutations also exhibited increased stability in the presence of sodium dodecyl sulfate (SDS) when compared to aprA-subtilisin. In addition to the above two mutations, the asparagine at position 76, located in the high affinity Ca(2+) binding loop of subtilisin, was changed to aspartic acid. The effect of this mutation on the thermal stability of the protein was examined at different calcium concentrations. The analog with all three mutations exhibited little dependence on calcium concentration below 1 mM levels, while the proteins without the mutation at asparagine-76 displayed a strong dependence of melting temperature on Ca(2+) concentration in this range. At much higher calcium concentrations, the analog with three mutations showed an increase in stability similar to that observed with aprA-subtilisin. The analog with three mutations also exhibited greater stability to SDS-induced denaturation than both aprA-subtilisin and the Ser109- and Ser218-substituted analogs. The activation energy barrier for loss of structure in 1% SDS for the analog with all three mutations was increased over that for aprA-subtilisin by 16 kcal/ml. These results suggest that the mutation of asparagine-76 to aspartic acid increases the affinity of the primary Ca(2+) binding site.

Circular Dichroism↗

PubMed1988

Insulin injection in the fetal rat: accelerated intrauterine growth and altered fetal and neonatal glucose homeostasis.

Fetal hyperinsulinemia is a well-known correlate of accelerated fetal growth; the consequences of fetal hyperinsulinemia upon fetal and neonatal glucoregulation are less well understood. We injected rat fetuses of a litter on day 18 of gestation with either 5 units of long acting insulin (I) or 154 mmol/L NaCl. Twelve hours after injection, the wet and dry mass of total body and liver of I fetuses significantly exceeded that of controls. At birth (day 21.5), newborn I pups weighed 5.86 +/- .08 g, and controls, 5.48 +/- .05 g, (P less than .001). On day 18, within one hour of injection, fetal plasma insulin concentrations were significantly elevated and remained so for 24 hours. Mothers of I fetuses had significant elevations of plasma insulin at 1, 3, and 6 hours, and they developed transient hypoglycemia. Plasma glucose concentrations in I fetuses were significantly diminished at 1, 3, and 6 hours and then achieved control levels by 12 hours. Fetal hypoglycemia resulted from an apparent direct effect of insulin upon fetal tissue and from the maternal hypoglycemia. Hypoglycemic I fetuses demonstrated a sluggish alpha-cell response; they failed to increase plasma glucagon one hour after insulin injection. Values were significantly increased three hours after injection. At birth, I pups became hypoglycemic relative to controls. This was, in part, due to their significantly elevated plasma insulin concentrations at 120 and 240 minutes (120 minutes, 43.8 +/- 8 v 17.5 +/- 6 microU/mL, P less than .001). Plasma glucagon was significantly increased in I pups at 240 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1988

Psychological sequelae of head injury.

Psychological disturbances are common after head injuries. A constellation of factors--organic, psychosocial and legal--may contribute to disability. Behavioural problems are not uncommon in children after head injuries. Developments in understanding the mechanisms that might lead to these complications have brought about improved management techniques.

Accidents, Traffic↗

PubMed1986

Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat.

We measured several growth stimulating variables in growth retarded (small-for-gestational-age [SGA]) rat fetuses on days 18, 19, 20, and 21 of their 21.5-day gestation. Bilateral maternal uterine artery ligation on day 18 was used to retard fetal growth, and fetuses of sham and nonoperated (normal) mothers served as controls. SGA fetuses had the lowest body and placental weights, while sham fetuses had intermediate weights from days 19 to 21. Similarly, SGA fetuses had the most profound alterations in arteriovenous PO2, PCO2, and pH, while sham fetuses had significant but less severe alterations. Fetal plasma concentrations and fetal/maternal ratios of glucose were significantly diminished in SGA fetuses on days 18 and 19; sham fetuses had intermediate values on day 19. Plasma concentrations and fetal/maternal ratios of leucine, isoleucine, and valine, but not the other amino acids, were significantly diminished in SGA fetuses on days 18, 19, and 20. Plasma insulin concentrations were significantly diminished in SGA fetuses on days 19 and 20, and hepatic concentrations of glycogen were significantly diminished on all days. Despite significantly elevated plasma glucagon concentrations in SGA fetuses, hepatic cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity was not elevated. These data indicate that bilateral uterine artery ligation retards fetal growth in the rat by altering gas exchange and limiting fuel availability. The limited insulin in SGA fetuses might further have retarded growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Branched-Chain↗

PubMed1985

Altered growth, hypoglycemia, hypoalaninemia, and ketonemia in the young rat: postnatal consequences of intrauterine growth retardation.

We characterized some of the consequences of intrauterine growth retardation in rat pups growth retarded [small for gestational age (SGA)] due to bilateral maternal uterine artery ligation. Pups of sham and nonoperated (normal) mothers served as controls. SGA pups had significantly reduced body and carcass mass throughout the study while body mass did not differ between sham and normal pups after 4 days. Brain mass was similar in the three groups at any age, while at 21 days and later, SGA liver weight as % body mass exceeded that of sham or normals. At 21 days, a 48-h fast reduced plasma glucose significantly in SGA compared to sham and normal pups; SGA plasma insulin was decreased and glucagon increased. Hepatic phosphoenolpyruvate carboxykinase activity and glycogen content were similar among groups. SGA pups did have significantly reduced plasma alanine and elevated betahydroxybutyrate levels. No differences in the responses to fasting occurred at 28 or 35 days. These data indicate that intrauterine growth retardation has profound effects on postnatal growth and metabolism.

3-Hydroxybutyric Acid↗

PubMed1985

Hypoglycemia in the newborn growth-retarded rat: delayed phosphoenolpyruvate carboxykinase induction despite increased glucagon availability.

We have characterized the sequential changes in plasma glucose, insulin and glucagon concentrations, and hepatic glycogen and phosphoenolpyruvate carboxykinase (PEPCK) during the first 240 min of life in rat pups growth retarded [small for gestational age (SGA)] due to bilateral maternal uterine artery ligation. Pups of sham and nonoperated (normal) mothers served as controls. SGA pups were smaller, had reduced liver mass, and demonstrated a pattern of hypoglycemia. They had significantly reduced plasma glucose concentrations at birth, 20, and 240 min but had normal values at 60 and 120 min. SGA pups had significantly reduced hepatic glycogen stores at birth. Plasma glucagon concentrations in SGA pups increased significantly at 20 and 60 min while insulin concentrations decreased equally in all groups. Hepatic PEPCK activity increased greatly in the sham and normal pups. SGA pups did not induce PEPCK during the first 240 min of life; however, pharmacologic doses of glucagon at birth accelerated PEPCK induction in SGA pups and prevented hypoglycemia. These data indicate that newborn SGA pups develop hypoglycemia because of limited hepatic glycogen stores and retarded gluconeogenesis. The delay in PEPCK induction in SGA pups may result from an inadequate although increased glucagon release at birth or diminished sensitivity to available glucagon.

Animals↗

PubMed1983

Ring chromosome 6: variability in phenotypic expression.

We present four children with a ring chromosome 6. Clinically, these cases are quite variable. A review of ten previously reported cases also suggests difficulty of phenotype-karyotype correlation in patients with a ring 6.

Adult↗

PubMed1982

Anti-immunoglobulin antibodies. III. Properties of sequential anti-idiotypic antibodies to heterologous anti-gamma globulins. Detection of reactivity of anti-idiotype antibodies with epitopes of Fc fragments (homobodies) and with epitopes and idiotopes (epibodies).

Murine anti-V region antibodies against a human monoclonal protein Gl with anti-gamma-globulin activity and bearing the Wa cross-reactive idiotype were prepared in several strains of mice. Antibodies were obtained that were specific for the Gl idiotype, the Wa cross-reactive idiotype, and for various framework antigenic determinants that were distinguished by a variety of procedures. Synthesis of such antibodies were found to be independent of MHC and Igh gene complexes. These anti-V region antibodies, produced by a majority of mouse strains investigated, also share a cross-reactive idiotype recognized by BALB/c anti-anti-V region Gl antibodies. A fraction of BALB/c anti-anti-V region Gl antibodies displayed human Fc gamma binding activity and, therefore, can be considered homobodies, as described in other systems. Two of the anti-idiotype antibodies obtained in this system exhibited a peculiar property: they interacted not only with their own antigen (IgM Gl), but also with the Fc fragment with which IgM Gl reacts. Thus, A/J anti-V region Gl antibodies bind to the human Fc gamma fragment in addition to IgM Gl. Similarly, a monoclonal CB6 F1 anti-anti-V region Gl antibody interacted with the V region of IgM Gl as well as with the syngeneic anti-V region antibodies. We called these anti-idiotypic antibodies epibodies because they interact with epitopes of the primary antigen. These homobodies and epibodies, obtained by immunization across heterologous barriers, represent new examples of recognition of the internal image of the antigen within the immune system.

Animals↗

PubMed1981

Utilization of prenatal genetic diagnosis in women 35 years of age and older in the United States, 1977 to 1978.

As a measure of access to and acceptability of prenatal chromosomal diagnosis among older gravidas, we determined the ratio of use of prenatal diagnosis among women 35 years of age and older in Alabama, California, Manhattan, and Nebraska for the period 1977-1978. Utilization ratios were higher in 1978. Overall, utilization ratios were between 6% and 28%, well below the adjusted rates of 40% to 50% found in certain United States and British localities. Urban women tended to have higher utilization ratios than had rural women, and white women had higher ratios than had black women. Ratios were extremely low for black and rural residents. The oldest women (those greater than or equal to 40 years), who were at fivefold greater risk than women 35 to 36 years of age, had less than a onefold increase in utilization over the latter groups. The vast majority of older gravidas initiated prenatal care sufficiently early in their pregnancies to receive prenatal diagnosis. Current program strategies need to ensure access to prenatal diagnosis, especially for women greater than or equal to 40 years of age, women who are black, and women who live in rural areas.

Adult↗

PubMed1980

Gonadal dysgenesis in a neonate with 45,X/47,XXX karyotype.

A case of X/XXX mosaicism in a neonate with dysgenetic gonads is presented because of the rarity of the X/XXX karyotype and the presence of dysgenetic ovaries and congenital heart anomalies. We suggest that the X/XXX mosaicism may not have a protective effect on the gonads as does X/XX mosaicism in some cases.

Female↗