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D E Comings

Publications and source records attributed to D E Comings.

At least 127 records · Page 7Linked to original sources
PubMed1982

Chinese hamster nuclear proteins. An electrophoretic analysis of interphase, metaphase and nuclear matrix preparations.

A comparison, by two-dimensional gel electrophoresis, of total interphase nuclear, metaphase chromosomal and nuclear matrix proteins from Chinese hamster V-79 cells was undertaken to examine the distribution of these proteins during mitosis. We have found a number of differences among these populations, although the two-dimensional gel patterns are generally similar. The most striking observation is that a loose cluster of six interphase nuclear polypeptides, with isoelectric points in urea between 5.7 and 6.7 and molecular masses ranging from 53 to 75 kDa, is greatly enriched in chromosome preparations. Each of these species is prominent also in the nuclear matrix. Preliminary evidence suggests that one of these polypeptides is the intermediate filament protein, vimentin. In addition, two major polypeptides of interphase nuclear preparations, a basic 94-kDa species and an approximately 65-kDa species, are absent from chromosomes. The latter polypeptide is the nuclear pore-lamina complex lamin B. Actin is present in all of these fractions, but tubulin has not been observed. hnRNP particle polypeptides are major components of the nuclear matrix, but are markedly reduced in metaphase chromosomes. The intermediate and basic 65-75-kDa nuclear matrix polypeptides we have previously demonstrated to be major components of rat liver nuclear matrix, are reduced in Chinese hamster matrix preparations and at least one of these species, a minor, basic, 68-kDa polypeptide, is missing entirely from metaphase chromosomes. These results are discussed in relation to nuclear and chromosome structure and the possibility of contamination of nuclear protein preparations from cultured cell lines with intermediate filaments.

Animals↗
PubMed1982

A case of familial exhibitionism in Tourette's syndrome successfully treated with haloperidol.

The authors describe a 32-year-old man with Gilles de la Tourette's syndrome whose most severe symptom was exhibitionism. Treatment with low doses of haloperidol eliminated all exhibitionistic urges. This patient's oldest son has multiple tics and his nephew has Tourette's syndrome with mild exhibitionism. The major implications of this case are that 1) all patients with compulsive-type exhibitionism should be carefully questioned about symptoms of Tourette's syndrome and, if positive, be given a trial regimen of haloperidol; 2) some patients with compulsive exhibitionism and no symptoms of Tourette's syndrome have a genetic, neurochemical disorder and respond to haloperidol.

Adult↗
PubMed1982

Two-dimensional gel electrophoresis of human brain proteins. V. Non-equilibrium gel electrophoresis, with detection of a myelin basic protein mutation--MBL-Duarte.

To examine the basic human brain proteins, we subjected 9 mmol/L urea extracts to non-equilibrium gel electrophoresis. The pattern observed differs distinctly from that with equilibrium gel electrophoresis. With this technique, the myelin proteins (myelin basic protein, proteolipids, and basic Wolfgram proteins) and many other unindentified major basic proteins can be demonstrated. The myelin basic proteins occur as two major polypeptides of different charge and slightly different molecular mass, indicating the action of at least two genes. The proteolipid proteins occur as a long series of charge isomers, suggesting multiple genes or extensive post-transcriptional modification. In one patient with schizophrenia, a charge-change mutation of the larger myelin basic protein (MBL) was observed and is termed "MBL-Duarte."

Brain Chemistry↗
PubMed1982

Two-dimensional gel electrophoresis of human brain proteins. I. Technique and nomenclature of proteins.

To understand at a molecular level the basis of the normal and pathological genetic differences between individuals it is necessary to begin a detailed two-dimensional gel electrophoretic mapping of the proteins of the human brain in normal individuals and those with various genetic neurological disorders. The present study is an examination of the polypeptide patterns of extracts of the human brain made with 9 mol/L urea solution. Details of the technique and the nomenclature of the patterns obtained are presented. the gels are separated into 20 sub-sections, based on standards with known molecular masses and isoelectric points. Groups of polypeptides within these sub-sections are identified by a number and a letter; the individual proteins are identified by a number. Thus, protein 1 in subsection 8, group b, would be designated 8b: 1. Subsequent papers in this series identify many of these proteins; show which proteins belong to the cytosol, synaptosome, myelin, and other brain fractions; show how these patterns vary between normal individuals and those with different neurological and psychiatric conditions; examine the effect of severe gliosis; and present the results of non-equilibrium gel electrophoresis for the more basic proteins.

Brain Chemistry↗
PubMed1982

Two-dimensional gel electrophoresis of human brain proteins. III. Genetic and non-genetic variations in 145 brains.

To determine the frequency of genetic mutations, polymorphisms, and non-genetic variation in the major human brain proteins, I examined, by equilibrium two-dimensional gel electrophoresis, 145 brains from patients dying of a wide variety of psychiatric, neurological, and non-neurological disorders. Of 176 polypeptides screened, there was one polymorphism of glial fibrillary acidic protein (GFAP-Duarte). Chi square analysis indicated it was non-randomly distributed among different diseases. A possible mutation associated with Joseph's disease is being further investigated. Three examples of a possible mutation of protein 8c:1 were noted. No other genetic mutations were observed. This low frequency of polymorphisms is consistent with results for two-dimensional gel analysis of other tissue and species. The numerous non-genetic variations are described.

Brain Chemistry↗
PubMed1982

Two-dimensional gel electrophoresis of human brain proteins. IV. Disorders of glial proliferation and a polymorphism of glial fibrillary acidic protein--GFAP Duarte.

Several genetic and non-genetic neurological disorders are characterized by neuronal cell death, followed by astrocytic glial cell proliferation. Because the major intermediate filament in astrocytes is glial fibrillary acidic protein (GFAP), large amounts of this protein accumulate. The two-dimensional gel-electrophoretic pattern of gliosed tissue is described. It shows a massive accumulation of the 50 000-dalton GFAP charge isomers (8e:1--8) plus a series of breakdown products of lower molecular mass and more-acid charge. In addition, I describe a genetic polymorphism, GFAP-Duarte, presenting as an additional, basic charge isomer of GFAP. The possibility that this or other mutations of GFAP may predispose certain neurons to premature cell death is discussed.

Brain Chemistry↗
PubMed1982

Two-dimensional gel electrophoresis of human brain proteins. II. Specific proteins and brain subfractions.

Brain proteins extractable with distilled water or 9 mol/L urea were subjected to two-dimensional gel electrophoresis. They are examined in relation to the identification of actin, tubulin, neurofilament proteins, glial fibrillary acidic protein; proteins of human embryonic neocortex, synaptosomes, myelin, and plasma; and rat neocortex, rat glial, and mouse neuroblastoma cell lines.

Actins↗
PubMed1981

Fibronectin from human germ-cell tumors resembles amniotic fluid fibronectin.

Three human germ-cell tumors established as xenografts in immunosuppressed mice were shown to produce fibronectin. Immunoperoxidase tissue staining with a specific antiserum revealed human fibronectin in some tumor cells. The cyst fluid which accumulated in the tumors contained human fibronectin as shown by a species-specific radioimmunoassay. Human fibronectin was isolated from two of the tumor fluids and compared to previously characterized fibronectins. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and gel electrofocusing showed that the germ-cell fibronectins resembled amniotic fluid fibronectin with regard to subunit molecular weight and isoelectric point. The distinct features of the amniotic fluid and germ-cell tumor fibronectin suggest that such fibronectins may provide new oncodevelopmental markers.

Amniotic Fluid↗
PubMed1981

Isolation of a non-histone chromosomal high mobility group protein from mouse liver nuclei by hydrophobic chromatography.

A histone-binding polypeptide of 25,000 Mr (J2) in the saline-EDTA wash of mouse liver nuclei was purified to homogeneity in three steps: 1) ammonium sulfate fractionation, 2) hydrophobic chromatography using omega-amino butyl agarose, and 3) DEAE-cellulose chromatography. The isolation conditions were mild, and avoided extremes of pH and use of chaotropic reagents. The purified polypeptide was similar, although not identical, to calf thymus HMG-1 (high mobility group protein). The molecular weight, migration in two-dimensional polyacrylamide gels, and the amino acid sequence of the first 9 residues of the NH2-terminal region were identical for the two proteins. The amino acid analysis, however, indicated the mouse liver polypeptide was more acidic, with a lower content of lysine and higher contents of serine, glutamic acid, and aspartic acid. The mouse liver and calf thymus proteins differ in extraction from nuclei and solubility at neutral pH. The J2 polypeptide reacted with affinity-purified HMG-1 antibody by complement fixation, but always at a lower level than the homologous antigen purified with chaotropic reagents. We conclude the J2 polypeptide is an HMG-1-like protein. The intrinsic hydrophobicity of HMG-1 may be important in its functional interaction with DNA and histones.

Amino Acids↗
PubMed1981

Huntington disease and Tourette syndrome. I. Electron spin resonance of bed ghosts.

Abnormalities in the electron spin resonance (ESR) of nitroxide-labeled red blood cell membranes have been reported in Huntington disease (HD). Because of the importance of verifying a general membrane defect in this disease, we have examined 13 unmedicated HD patients of all grades of severity, with a duration of symptoms from 3 to 20 years and including juvenile and rigid cases. No significance differences in the ESR of controls, HD patients, and three Tourette syndrome patients were found.

Adolescent↗
PubMed1981

Huntington disease and Tourette syndrome. II. Uptake of glutamic acid and other amino acids by fibroblasts.

Injection of kainic acid, a rigid analog of the excitatory neurotransmitter glutamic acid (glu), into the neostriatum of rats produces a condition that mimics Huntington disease (HD) in at least 12 different morphological and biochemical parameters. These results suggested that one of the possible basic mechanisms in HD is a defect in the presynaptic of glial uptake of glu, resulting in chronic hyperstimulation and death of a specific set of neurons. To test this hypothesis, the uptake of glu was studied in 12 carefully matched sets of control-HD pairs and two lines of Tourette syndrome fibroblasts. Although the first six sets suggested a glutamate transport defect in HD cells, examination of 12 sets indicated that there were no significant differences between control and HD cells. The fibroblasts showed both a high and low affinity uptake of glutamic acid. Sodium dependent uptake of L-glutamate (L-glu) minus D-glutamate (D-glu) at 100, 1,000, and 10,000 Micrometers glutamate was normal in HD and Tourette syndrome cells.

Adolescent↗
PubMed1981

Homozygosity for Pc 1 Duarte-like protein in primates and other animals.

Pc 1 Duarte is a mutant brain protein present in 32% of the normal human population with 2.6% being homozygous. Preliminary studies suggest an increased frequency of this mutation in individuals with affective disease. To determine if this mutant was present in primates, 32 fetal (wild)-born baboons were examined. All 32 were homozygous for a Pc 1 Duarte-like protein.

Animals↗