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S M Shields

Publications and source records attributed to S M Shields.

7 recordsLinked to original sources
PubMed1992

The human pattern ERG: alteration of response properties with aging.

The influence of aging on both the amplitude and the latency of transient and steady-state pattern electroretinograms (PERG's) was studied in 80 healthy participants ranging from 25 to 77 years of age (mean age, 55.3 years). Responses to counterphasing checkerboard patterns were recorded for each of 7 test conditions in which the spatial (i.e., check sizes 0.25, 0.50, 1.00, and 2.00 degrees) and temporal characteristics (i.e., counterphasing at either 2, 4, 8, or 16 rps) of the stimuli were varied. For both the transient and steady-state PERG's amplitude was inversely related to age (p less than 0.05 for each test condition). In general, PERG latency directly correlated with age, but this effect was less robust (p less than 0.05 for one transient condition and three of the four steady-state conditions). The influence of age on the spatial tuning of the PERG was minimal; the decrease in PERG amplitude and the increase in PERG latency as a function of age were essentially the same for all test conditions. However, the magnitude of the age-related reduction in PERG amplitude was observed to vary with temporal frequency, being largest for the steady-state condition (16 rps). The results from an experiment in which young subjects were tested while wearing opaque contact lenses with 2-mm artificial pupils suggest that senile miosis is a significant factor contributing to the age-related PERG amplitude and latency changes, but it does not fully account for the observed changes.

Adult↗
PubMed1987

Segregation of inverted chromosome 13 in families ascertained through liveborn recombinant offspring.

In humans pericentric inversions are rare structural chromosome abnormalities. Reproductive consequences of inversion heterozygosity depend upon many variables such as the chromosomes involved, the location of breakpoints, frequency of crossovers in the inverted segment, functional impairment of the gametes produced, and the viability of unbalanced zygotes that form. Therefore, each pericentric inversion may be studied as a unique mutation. This paper analyzes the segregation of inversion 13 chromosomes resulting from breaks at bands 13p12 and 13q21/22 in 11 apparently unrelated families. Ten of these families were ascertained through malformed fetuses or infants with a recombinant 13 duplication q, deletion p chromosome.

Abnormalities, Multiple↗
PubMed1985

Calmodulin-dependent protein phosphorylation in synaptic junctions.

Synaptic junctions (SJs) from rat forebrain were examined for Ca2+/calmodulin (CaM)-dependent kinase activity and compared to synaptic plasma membrane (SPM) and postsynaptic density (PSD) fractions. The kinase activity in synaptic fractions was examined for its capacity to phosphorylate endogenous proteins or exogenous synapsin I, in the presence or absence of Ca2+ plus CaM. When assayed for endogenous protein phosphorylation, SJs contained approximately 25-fold greater amounts of Ca2+/CAM-dependent kinase activity than SPMs, and fivefold more activity than PSDs. When kinase activities were measured by phosphorylation of exogenous synapsin I, SJs contained fourfold more activity than SPMs, and 10-fold more than PSDs. The phosphorylation of SJ proteins of 60- and 50-kilodalton (major PSD protein) polypeptides were greatly stimulated by Ca2+/CaM; levels of phosphorylation for these proteins were 23- and 17-fold greater than basal levels, respectively. Six additional proteins whose phosphorylation was stimulated 6-15-fold by Ca2+/CAM were identified in SJs. These proteins include synapsin I, and proteins of 240, 207, 170, 140, and 54 kilodaltons. The 54-kilodalton protein is a highly phosphorylated form of the major PSD protein and the 170-kilodalton component is a cell-surface glycoprotein of the postsynaptic membrane that binds concanavalin A. The CaM-dependent kinase in SJ fractions phosphorylated endogenous phosphoproteins at serine and/or threonine residues. Ca2+-dependent phosphorylation in SJ fractions was strictly dependent on exogenous CaM, even though SJs contained substantial amounts of endogenous CaM (15 micrograms CaM/mg SJ protein). Exogenous CaM, after being functionally incorporated into SJs, was rapidly removed by sequential washings. These observations suggest that the SJ-associated CaM involved in regulating Ca2+-dependent protein phosphorylation may be in dynamic equilibrium with the cytoplasm. These findings indicate that a brain CaM-dependent kinase(s) and substrate proteins are concentrated at SJs and that CaM-dependent protein phosphorylation may play an important role in mechanisms that underlie synaptic communication.

Amino Acids↗
PubMed1985

Identification of protein phosphatase 1 in synaptic junctions: dephosphorylation of endogenous calmodulin-dependent kinase II and synapse-enriched phosphoproteins.

A calcium/calmodulin-dependent protein kinase termed CaM-kinase II is a major component of synaptic junctions from forebrain and constitutes approximately 12% of total synaptic junction protein. CaM-kinase II phosphorylates at least seven polypeptides that are enriched in synaptic junctions, of which two represent the 50- and 60-kilodalton subunits of the protein kinase. In this report the nature of endogenous protein phosphatases which dephosphorylate each of the seven synaptic junction phosphoproteins was examined. Assays of synaptic junctions and other subcellular fractions from rat forebrain for type-1 and type-2 protein phosphatases revealed that protein phosphatase 1 (PrP-1) was specifically enriched in synaptic junctions with respect to cytosolic fractions. The activity of type-2 protein phosphatases was very low in synaptic junctions. Homogeneous PrP-1 from rabbit skeletal muscle was found to dephosphorylate each of the seven phosphoproteins in synaptic junctions. Inhibitors-1 and -2 were found to inhibit endogenous protein phosphatase activity by 70 to 80%. Since inhibitors-1 and -2 are specific inhibitors of PrP-1, these results indicate that this enzyme accounts for the majority of endogenous protein phosphatase activity in synaptic junctions. Approximately 15% of the protein phosphatase activity in synaptic junctions was type 2A, whereas PrP-2B and PrP-2C accounted for little, if any, of the activity toward endogenous or exogenous phosphoproteins. These results indicate that PrP-1 may be important in controlling the state of phosphorylation of synaptic junction proteins.

Animals↗
PubMed1984

Autophosphorylation of calmodulin-kinase II in synaptic junctions modulates endogenous kinase activity.

Previous studies have purified from brain a Ca2+/calmodulin-dependent protein kinase II (designated CaM-kinase II) that phosphorylates synapsin I, a synaptic vesicle-associated phosphoprotein. CaM-kinase II is composed of a major Mr 50K polypeptide and a minor Mr 60K polypeptide; both bind calmodulin and are phosphorylated in a Ca2+/calmodulin-dependent manner. Recent studies have demonstrated that the 50K component of CaM-kinase II and the major postsynaptic density protein (mPSDp) in brain synaptic junctions (SJs) are virtually identical and that the CaM-kinase II and SJ 60K polypeptides are highly related. In the present study the photoaffinity analog [alpha-32P]8-azido-ATP was used to demonstrate that the 60K and 50K polypeptides of SJ-associated CaM-kinase II each bind ATP in the presence of Ca2+ plus calmodulin. This result is consistent with the observation that these proteins are phosphorylated in a Ca2+/calmodulin-dependent manner. Experiments using 32P-labeled peptides obtained by limited proteolysis of 60K and 50K polypeptides from SJs demonstrated that within each kinase polypeptide the same peptide regions contain both autophosphorylation and 125I-calmodulin binding sites. These results suggested that the autophosphorylation of CaM-kinase II could regulate its capacity to bind calmodulin and, thus, its capacity to phosphorylate substrate proteins. By using 125I-calmodulin overlay techniques and sodium dodecyl sulfate-polyacrylamide gel electrophoresis we found that phosphorylated 50K and 60K CaM-kinase II polypeptides bound more calmodulin (50-70%) than did unphosphorylated kinase polypeptides. Levels of in vitro CaM-kinase II activity in SJs were measured by phosphorylation of exogenous synapsin I. SJs containing highly phosphorylated CaM-kinase II displayed greater activity in phosphorylating synapsin I (300% at 15 nM calmodulin) relative to control SJs that contained unphosphorylated CaM-kinase II. The CaM-kinase II activity in phosphorylated SJs was indistinguishable from control SJs at saturating calmodulin concentrations (300-1,000 nM). These findings show that the degree of autophosphorylation of CaM-kinase II in brain SJs modulates its in vitro activity at low and possibly physiological calmodulin concentrations; such a process may represent a mechanism of regulating this kinase's activity at CNS synapses in situ.

Adenosine Triphosphate↗
PubMedDate not supplied

Mosaic trisomy 8: a cautionary note regarding missed antenatal diagnosis.

Chromosomal analysis of fetal cells is a commonly used, safe, and highly accurate procedure. The rate of false-negative results is unknown. Recent experience at four centers suggests that there may be a particular likelihood for mosaic trisomy 8 to be missed with routine antenatal diagnostic procedures. This report reviews these cases, the characteristic findings of mosaic trisomy 8, and the tissue-specific differential yield of chromosomal analysis that may contribute to the increased risk of missed antenatal diagnosis in patients with this disorder.

Chromosomes, Human, Pair 8↗