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Biomedical subjects

F B Palmer

Publications and source records attributed to F B Palmer.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cell-specific fatty acylation of proteins in cultured cells of neuronal and glial origin.

Distinct sets of cellular proteins were labeled with [3H]myristic and [3H]palmitic acids in primary (rat neurons and astroglia) and continuous (murine N1E-115 neuroblastoma and rat C6 glioma) cell cultures derived from the nervous system. Both soluble and membrane proteins were modified by myristate in a hydroxylamine-stable (amide) linkage, while palmitoylated proteins were ester-linked and almost exclusively membrane bound. Chain elongation of both labeled fatty acids prior to acylation was observed, but no protein amide-linked [3H]myristate originating from [3H]palmitate was detected. Fatty acylation profiles differed considerably among most of the cell lines, except for rat astroglial and glioma cells in which myristoylated proteins appeared to be almost identical based on SDS gel electrophoresis. An unidentified 47 kDa myristoylated protein was labeled to a significantly greater extent in astroglial than in glioma cells; the expression of this protein could be related to transformation or development in cells of glial origin.

Acylation↗
PubMed1989

Giftedness. Can it be predicted in infancy?

A cohort of 200 children, who were followed from birth and periodically evaluated as part of a longitudinal study of child development, was used to determine the ability of the Bayley Scales of Infant Development (BSID) to predict children who would be considered intellectually gifted at 7.5 years. The cohort was predominantly white (91%), upper middle class (70% in Hollingshead class 1 or 2), and had preschool educational experiences (94%). At outcome, 36 children had WISC-R verbal, performance, or full scale IQs greater than 135 and were called gifted. On average, gifted children walked 0.7 months earlier and spoke two-word sentences 2.2 months earlier than the non-gifted group. As a group, gifted children showed statistically significant, but clinically small, advantages for age of walking, age of speaking two-word sentences, BSID, and Stanford Binet IQ. Of the 36 children who later proved to be gifted, only two had BSID IQs greater than 134. Of the four children who had BSID IQs greater than 134, two maintained their superior function but 2 did not. A discriminant function analysis was used to predict giftedness for individual children based on BSID performance. The resulting classification achieved sensitivity = 0.69 and specificity = 0.39. Although groups of infants who will be gifted have higher BSID scores, the BSID cannot be endorsed as a method of identifying individual infants who will later demonstrate superior cognitive function.

Child↗
PubMed1988

Isolation of plasma membranes from cultured glioma cells and application to evaluation of membrane sphingomyelin turnover.

A rapid and reliable method for the isolation of plasma membranes and microsomes of high purity and yield from cultured glioma cells is described. The procedure involves disruption by N2 cavitation, preliminary separation by centrifugation in Tricine buffer, and final separation on a gradient formed from 40% Percoll at pH 9.3. Enzyme and chemical markers indicated greater than 60% yield with six- to eightfold enrichment for plasma membranes and greater than 25% yield with three- to fourfold enrichment for a microsomal fraction consisting mainly of endoplasmic reticulum. The final fractions were obtained with high reproducibility in less than 1 h from the time of cell harvesting. Application of this procedure to human fibroblasts in culture is assessed. The isolation procedure was applied to investigations of synthesis and turnover of sphingomyelin and phosphatidylcholine in plasma membranes of glioma cells following incubation for 4-24 h with [methyl-3H]choline. These studies indicated that radioactivity from phosphatidylcholine synthesized in microsomes from exogenous choline may serve as a precursor of the head-group of sphingomyelin accumulating in the plasma membrane.

Biomarkers↗
PubMed1988

The effects of physical therapy on cerebral palsy. A controlled trial in infants with spastic diplegia.

Legislatively mandated programs for early intervention on behalf of handicapped infants often stipulate the inclusion of physical therapy as a major component of treatment for cerebral palsy. To evaluate the effects of physical therapy, we randomly assigned 48 infants (12 to 19 months of age) with mild to severe spastic diplegia to receive either 12 months of physical therapy (Group A) or 6 months of physical therapy preceded by 6 months of infant stimulation (Group B). The infant-stimulation program included motor, sensory, language, and cognitive activities of increasing complexity. Masked outcome assessment was performed after both 6 and 12 months of therapy to evaluate motor quotient, motor ability, and mental quotient. After six months, the infants in Group A had a lower mean motor quotient than those in Group B (49.1 vs. 58.1, P = 0.02) and were less likely to walk (12 vs. 35 percent, P = 0.07). These differences persisted after 12 months of therapy (47.9 vs. 63.3, P less than 0.01, and 36 vs. 73 percent, P = 0.01, respectively). We noted no significant differences between the groups in the incidence of contractures or the need for bracing or orthopedic surgery. Group A also had a lower mean mental quotient than Group B after six months of therapy (65.6 vs. 75.5, P = 0.05). The routine use of physical therapy in infants with spastic diplegia offered no short-term advantage over infant stimulation. Because of the limited scope of the trial, our conclusions favoring infant stimulation are preliminary. The results suggest that further study of the effects of both physical therapy and infant stimulation is indicated.

Cerebral Palsy↗
PubMed1988

Sodium channel activation does not alter lipid metabolism in cultured neuroblastoma cells.

The interaction of voltage-sensitive Na+-channels and membrane lipid metabolism was examined by incubating cultured neuroblastoma cells with neurotoxins which alter the voltage-dependent relationship between the closed and open conformation of the channel protein. Guanidinium flux rate, a measure of Na+-channel activation, was increased 10-fold by the combined action of veratridine (100 microM) and scorpion venom (28 micrograms/ml). This response was completely blocked by tetrodotoxin (1 microM). Under the same experimental conditions, the toxins did not increase the efflux of [3H]arachidonic acid from prelabeled cell membrane lipids or stimulate uptake of exogenous [3H]arachidonic acid. In addition, altering membrane fatty acid composition by incubating cells for 24 hr in a medium containing 50 microM arachidonic or oleic acid did not alter guanidinium flux rates relative to that of control cultures. When cells were pulsed with 32Pi for 60 min and stimulated by veratridine plus scorpion venom for an additional 30 min, uptake of 32Pi into phosphatidylinositol was reduced; stimulating cells with bradykinin, a receptor agonist which activates the inositol cycle, promoted a 3.8 fold increase. Polyphosphoinositide turnover was not affected by Na+-channel activation, but was stimulated by bradykinin. These results suggest that voltage-sensitive Na+-channel activation in cultured neuroblastoma cells can function independent of membrane phospholipid and fatty acid metabolism.

Arachidonic Acids↗
PubMed1988

Soluble and membrane-bound polyphosphoinositide phosphohydrolases in mammalian erythrocytes.

Phosphatases and phosphodiesterases that hydrolyse polyphosphoinositides are described in both membrane and cytosol fractions of human, pig, rat, rabbit, and sheep erythrocytes using exogenous substrates. With suitably optimized assay conditions, Ca2+-dependent phosphatidylinositol bisphosphate (PIP2) phosphodiesterase activity was found in the hemoglobin-free cytosol fraction, as well as the membrane. Membrane activity is completely dependent upon Triton X-100 and salt and inhibited by cetyltrimethylammonium bromide (CTAB), while the soluble activity requires CTAB and is inhibited by Triton. A low Ca2+-dependent PIP2 phosphatase activity, not present in other tissues, was also detected. The cation-independent phosphatidylinositol phosphate (PIP) phosphatase is localized in the membrane in most species, while the diesterase and the PIP2 phosphatases (both Mg2+ and Ca2+ dependent) are localized in the cytosol. Rat and rabbit erythrocytes are atypical in having a substantial proportion of their Mg2+-dependent PIP2 phosphatase activities in the membrane. All activities are lowest in sheep erythrocytes, except the PIP phosphatase, most of which is soluble in this species. Ca2+-dependent PIP2 phosphatase activity is not correlated with the activity or subcellular distribution of any of the other hydrolases and seems to be a separate enzyme. All the phosphoinositide hydrolase activities, particularly the diesterase, are orders of magnitude lower in erythrocytes than in other tissues. Both soluble and membrane diesterase activities are lost as erythrocytes age. Soluble polyphosphoinositide diesterase does not seem to be active with membrane-bound substrate, since pig and sheep erythrocytes that have negligible membrane activity do not respond to Ca2+ loading, yet have substantial diesterase activity in the cytosol. This supports the view that the diesterase is not physiologically functional in normal erythrocytes.

Animals↗
PubMed1987

Identification of the phosphomonoesterases that hydrolyze lysopolyphosphoinositides in rat brain and liver.

The phosphatase activities responsible for the sequential dephosphorylation of lysophosphatidylinositol 4,5-bisphosphate (lysoPtdIns(4,5)P2) to lysophosphatidylinositol that precedes reacylation in rat brain and liver microsomes were characterized. LysoPtdIns(4,5)P2 and the intermediate lysophosphatidylinositol 4-phosphate (lysoPtdIns4P) were hydrolyzed by two distinct phosphatase activities which were distinguishable by their substrate and cation requirements. The lysoPtdIns(4,5)P2 phosphatase activity was Mg2+ dependent and partially inhibited by Ca2+, excess Mg2+, and cationic detergent (cetyltrimethylammonium bromide). Activity was maximal at neutral (brain) or slightly alkaline (liver) pH when the Mg2+/lysoPtdIns(4,5)P2 molar ratio was 1.0 in the presence of bovine serum albumin (1 mg.mL-1). LysoPtdIns4P phosphatase activity did not require divalent cations (not inhibited by EDTA). This activity was inhibited by Ca2+, Mg2+, and substrate concentrations above 0.2 mM. Maximum activity was observed over a broad pH range (6.0-8.5). Both activities were inhibited by lysophosphatidylinositol and lysophosphatidylcholine, but not other lysophospholipids. The lysopolyphosphoinositides are most likely hydrolyzed by the same phosphatases that act on the diacylpolyphosphoinositides, since PtdIns(4,5)P2 and PtdIns4P were also hydrolysed by Mg2+-dependent and cation-independent phosphatases, respectively. Activities with the diacylpolyphosphoinositides differed only in their requirement of detergents for maximum activity in vitro. Specific activities for the diacyl and "lyso" forms of each substrate were very similar when suitably optimized reaction mixtures were used. The subcellular distributions of the two phosphatase activities in both brain and liver were the same when acting on diacyl- or lyso-polyphosphoinositides, as was their response to inhibitors. Alkaline, acid, phosphoprotein, and inositol-1-phosphate phosphatases did not contribute substantially to the hydrolysis of either lysoPtdIns4P or lysoPtdIns(4,5)P2, since the activities were not significantly inhibited by cysteine, dithiothreitol, NaF, or LiCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The Clinical Linguistic and Auditory Milestone Scale (CLAMS). Identification of cognitive defects in motor-delayed children.

The Clinical Linguistic and Auditory Milestone Scale (CLAMS) and Bayley Scales of Infant Development (BSID) were independently administered to 43 children with mild-to-moderate motor delay at 15, 21, and 27 months of age. Highly significant correlations were noted for each examination. Sex, race, and age at time of examination did not significantly influence the relationship between a CLAMS quotient and a Bayley ratio quotient (BRQ). On the first examination gestational age exerted an effect that carried over to the total population. The initial CLAMS quotient also correlated with the results of the CLAMS and BSID administered 12 months later. The CLAMS identified children with a delayed BRQ (less than 70) as follows: sensitivity, 0.66; specificity, 0.79; predictive value of a positive test, 0.80; and predictive value of a negative test, 0.65. The CLAMS provides the pediatrician with a language assessment instrument that adequately detects cognitive deficits in motor-delayed children.

Child Language↗
PubMed1986

Clinical linguistic and auditory milestone scale: prediction of cognition in infancy.

At each well-child examination between birth and two years, parents of 448 infants were questioned about their child's age at attainment of 25 linguistic and auditory milestones. Parental reports were compared with the results of independently administered Bayley Mental Developmental Index (MDI) at one year of age. Parental recall of information was high, ranging from 70 to 99 per cent for 21 of the 25 milestones. The milestone performance of infants with normal MDI scores showed an orderly, sequential progression of expressive and receptive language. Across the entire population studied, the correlation between milestone attainment and MDI was statistically significant for 24 of the 25 milestones, and later attainment of milestones correlated with lower MDI. As a group, 'delayed' infants (MDI less than 68) attained milestones significantly later than 'average' infants (MDI 85 to 116) for 20 of 25 items. Attention to linguistic and auditory milestones early in infancy can contribute to the early detection and diagnosis of mental retardation and disorders of communication.

Auditory Perception↗
PubMed1986

Metabolism of lysopolyphosphoinositides by rat brain and liver microsomes.

Lysophosphatidylinositol 4,5-bisphosphate has been reported to form ion-conducting channels in artificial membranes. If formed in vivo, mechanisms for its removal from cellular membranes would be required. Thus, possible pathways were explored in rat brain and liver microsomes. Since neither lysophosphatidylinositol 4-phosphate nor lysophosphatidylinositol 4,5-bisphosphate were acylated in experiments with [3H]arachidonic acid or [14C]oleoyl CoA, polyphosphoinositides do not participate directly in a deacylation-reacylation cycle as proposed for the postsynthesis enrichment of phosphatidylinositol with arachidonic acid. Similar enrichment in polyphosphoinositides can occur only via the rapid phosphorylation-dephosphorylation cycle linking all three phosphoinositides. Lysophosphatidyl[2-3H]inositol 4,5-bisphosphate and lysophosphatidyl[2-3H]inositol 4-phosphate were rapidly dephosphorylated to 1-acyl-sn-glycero(3)phospho(1)-D-myo-inositol by microsomes from both tissues. Appearance of only trace quantities of radioactive lysophosphatidylinositol monophosphate during the catabolism of lysophosphatidyl[2-3H]inositol 4,5-bisphosphate indicated that the second dephosphorylation step, which was cation independent, was at least as fast as the first step which required Mg2+. In the presence of ATP, CoA, and arachidonic acid, the lysophosphatidylinositol was converted to phosphatidylinositol. This acylation reaction was rate limiting in brain microsomes. Dephosphorylation of lysophosphatidylinositol 4,5-bisphosphate was rate limiting in liver microsomes. Neither the lysopolyphosphoinositides nor the lysophosphatidylinositol produced from them in the reactions were degraded by acyl hydrolases or phosphodiesterases in microsomes from either tissue. Therefore, any lysopolyphosphoinositide formed in vivo would probably be removed by dephosphorylation and recycled to phosphatidylinositol.

Animals↗
PubMed1985

An enzymatically coupled assay for rat brain polyphosphoinositide phosphodiesterase in an optimized reaction mixture.

Bovine intestinal alkaline phosphatase was found to hydrolyze inositol phosphates many times faster than the monoester phosphate groups of the polyphosphoinositides. A convenient and sensitive in vitro assay for the Ca2+-dependent polyphosphoinositide phosphodiesterase was devised in which inositol trisphosphate released from exogenous phosphatidylinositol 4,5-bisphosphate was hydrolyzed by alkaline phosphatase. The resulting inorganic phosphate was measured by an automated method after solubilization of the reaction mixture with sodium dodecyl sulfate. The phosphodiesterase was maximally stimulated by combining the known positive effects of cetyltrimethylammonium bromide (at the optimum detergent-to-substrate ratio of 2.3), monovalent cations (0.1 M KCl), and Ca2+ (0.5 mM) with the additional enhancement by Triton X-100 (0.2% w/v). Activities obtained for rat brain homogenates and microsomal and cytosol fractions were 126 +/- 3.8 (17), 110 +/- 5.7 (10), and 252 +/- 15.5 (8) nmol X min-1 X mg protein-1 (mean +/- SE for n determinations), respectively.

Alkaline Phosphatase↗
PubMed1985

Normal gross motor development: the influences of race, sex and socio-economic status.

The ages at attainment of 12 gross motor milestones were obtained prospectively during well-baby visits in the first two years of life for 381 children. All had been born at term and were judged to be normal at one year. A longitudinal analysis, using an index summarizing each child's progress for eight selected milestones, is reported for the 284 children for whom data were complete. A high percentage of parents were able to report the age at attaining milestones with an acceptable degree of variability. The children attained milestones at earlier ages than traditionally reported. There were only minor sex differences in age at attainment, but black children attained milestones earlier than white children.

Analysis of Variance↗
PubMed1985

Polyphosphoinositide metabolism in aging human erythrocytes.

Normal human erythrocytes were fractionated in a density gradient. Capacity to metabolize polyphosphoinositides was compared in young (least dense) and old (most dense) cells. Polyphosphoinositide synthesis was assessed by following the incorporation of radioactivity from [gamma-32P]ATP into the 1-(3-sn-phosphatidyl)-D-myo-inositol 4-phosphate (PtdIns4P) and 1-(3-sn-phosphatidyl)-D-myo-inositol 4,5-bisphosphate (PtdIns(4,5)P2) of isolated membranes. There was no significant age-dependent change in the ability to synthesize PtdIns4P and PtdIns(4,5)P2 or in the response of the PtdIns and PtdIns4P kinases to Mg2+. The cytosolic Mg2+-dependent PtdIns(4,5)P2 phosphatase was also unaffected by age. The membrane cation-independent PtdIns4P phosphatase activity declined slightly (12%). Therefore, the capacity to catalyse the interconversion among the three phosphoinositides in the membrane is retained throughout the life of the erythrocyte. The Ca2+-dependent polyphosphoinositide phosphodiesterase activity in the membranes was reduced in old cells (57%) to the same extent as the glutamate-oxaloacetate transaminase activity used as an index of cell age. Thus, irreversible loss of polyphosphoinositide from the membrane by the action of this diesterase (prevented in healthy cells by the active maintenance of a very low intracellular Ca2+ concentration) is not very likely even in senescent cells when Ca2+ homeostasis begins to fail.

Adenosine Triphosphatases↗
PubMed1985

The diagnostic value of the neurodevelopmental examination.

The neurodevelopmental examination is a pediatric approach to developmental diagnosis that relies on evaluation of multiple streams of development. The value of the neurodevelopmental examination for the early diagnosis of cerebral palsy and mental retardation was studied by a retrospective analysis of prospectively (longitudinally) collected data. Both conditions were found to be accurately diagnosed in the first year of life. For cerebral palsy, sensitivity was 0.81 and specificity 1.00; for mental retardation, sensitivity was 0.56 and specificity 0.96. The trained pediatrician can make early diagnoses of developmental disabilities.

Cerebral Palsy↗