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D Patterson

Publications and source records attributed to D Patterson.

At least 55 records · Page 3Linked to original sources
PubMed1990

Physical mapping of chromosome 21 DNA markers in Alzheimer's disease region using somatic cell hybrids.

From a chromosome 21 phage library, we selected 10 clones located proximal of the senile plaque amyloid precursor protein gene. Since a locus for Alzheimer's disease (AD) has been localized in the pericentromeric region of chromosome 21, the selected phage clones are potential candidate probes for genetic analysis of AD. In this study, we subcloned single-copy fragments of the selected phage clones, refined their physical localization, and examined their chromosomal distribution in relation to their position on chromosome 21. The results indicated that the phage clones are identifying nine chromosome 21 loci, which, if polymorphic, may be helpful in localizing the AD locus more precisely. Moreover, since all phage clones are located close to the centromere of chromosome 21, they can be used to determine the parental origin of nondisjunction in trisomy 21 with high reliability.

Alzheimer Disease↗
PubMed1989

Effect of nitrous oxide inactivation of vitamin B12-dependent methionine synthetase on the subcellular distribution of folate coenzymes in rat liver.

The effects of nitrous oxide inactivation of the vitamin B12-dependent enzyme, methionine synthetase (EC 2.1.1.13), on the subcellular distribution of hepatic folate coenzymes was determined. In controls, cytosolic folates were 5-methyltetrahydrofolate (45%), 5- and 10-formyltetrahydrofolate (9 and 19%, respectively), and tetrahydrofolate (27%). Exposure of rats to an atmosphere containing 80% nitrous oxide for 18 h resulted in a marked shift in this distribution pattern to 5-methyltetrahydrofolate, 84%; 5- and 10-formyltetrahydrofolate, 2.1 and 9.1%, respectively; and tetrahydrofolate, 4.7%. Activity of the cytosolic enzyme, methionine synthetase, was reduced by about 84% as compared to that of air breathing controls. In controls, mitochondrial folates were 5-methyltetrahydrofolate (7.3%), 5- and 10-formyltetrahydrofolate (11.5 and 33.1%, respectively), and tetrahydrofolate (48.1%). This distribution did not change after exposure to nitrous oxide. These results show that the effects of nitrous oxide inactivation of vitamin B12 are confined to the cytosol, at least in the short term, and suggest that there is little, if any, transport of free folates between the cytosolic and mitochondrial compartments.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1989

Characterization of an unusual and complex chromosome 21 rearrangement using somatic cell genetics and cloned DNA probes.

In a previous case of a newborn infant with typical Down syndrome, chromosome analysis indicated the presence of an unusual and complex translocation of chromosome 21. The patient's cells contained one normal chromosome 21 and a rearranged, F group-sized submetacentric chromosome. This abnormal chromosome appeared to involve duplication of the distal portion of 21q with translocation to the short arm, and a deletion of C-band-positive centromeric heterochromatin. Using linearly ordered cloned DNA probes, we report the detailed molecular examination of this abnormal chromosome, which has been isolated on a hamster background in a hybrid cell line. Both short arm and pericentromeric sequences are present on this chromosome, as well as distal 21q sequences. However, a substantial portion of proximal 21q is deleted. The distal boundary of this deleted section can be pinpointed within the region between two loci (D21S8 and D21S54), a distance of about 5,000 kb. This study illustrates the power of using precisely mapped, linearly ordered DNA probes to characterize this type of rearrangement. In addition, this hybrid cell line can also be used as a member of a mapping panel to map DNA sequences regionally on chromosome 21.

Animals↗
PubMed1989

Mapping of the gene encoding the multifunctional protein carrying out the first three steps of pyrimidine biosynthesis to human chromosome 2.

The CAD gene encodes a trifunctional protein that carries the activities of the first three enzymes (carbamyl phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase) of de novo pyrimidine biosynthesis. Genomic fragments of the human CAD gene have been obtained by screening a human genomic library in bacteriophage lambda using a Syrian hamster cDNA clone as a probe. These human genomic clones have been used to assign the CAD gene to human chromosome 2 using in situ hybridization to human metaphase chromosomes and Southern blot hybridization analysis of DNA isolated from a panel of Chinese hamster/human hybrid cells. In situ hybridization analysis has allowed further localization of this gene to the chromosomal region 2p21-p22.

Amidohydrolases↗
PubMed1989

Drosophila purine auxotrophy: new alleles of adenosine 2 exhibiting a complex visible phenotype.

New mutant alleles of the adenosine2 locus (ade2; 2-17.7) have been isolated using the eye-color phenotype exhibited by the prototype auxotrophic allele ade2 as the screening criterion. The new mutants form a single complementation group, suggesting that they all exhibit purine auxotrophy and defective formylglycineamide ribotide amidotransferase enzyme, like ade2. Tests carried out on particular new alleles confirm these suggestions. The new mutants all exhibit more extreme physical defects than the prototype. They have wing abnormalities like mutants defective in pyrmidine biosynthesis and reduced bristles like those defective in protein synthesis; thus they exhibit the combined visible phenotype of rudimentary wings, rosy eyes, and bobbed bristles. Cytogenetic analysis places the locus in the interband proximal to 26B1-2.

Adenosine↗
PubMed1989

Aging: effect on hepatic metabolism and transport of folate in the rat.

Effects of aging on hepatic folate metabolism and transport were assessed in male Fisher 344 rats. Total serum and hepatic folate levels were measured. Hepatic folates were measured by high-performance liquid chromatography and by Lactobacillus casei assay. Transport of 5-methyltetrahydrofolate (5-CH3-H4PteGlu) was measured in isolated hepatocytes. Serum folate declined with aging; however, neither the total folate level nor the distribution of hepatic folate coenzymes was affected by the aging process. The level of liver folate monoglutamates was not significantly different in any group. The initial rate of uptake of 5-CH3-H4PteGlu was significantly decreased in hepatocytes from the 24-mo-old rats, as was the ability to concentrate this folate from the medium. Aged rats maintain apparently normal levels of hepatic folates despite decreased serum levels and decreased ability to take up folates, suggesting that membrane transport of folates may not be a limiting factor in hepatic folate assimilation.

Aging↗
PubMed1989

Effects of extracorporeal shock wave lithotripsy on single chamber rate response and dual chamber pacemakers.

This study evaluated effects of extracorporeal shock wave lithotripsy on four models of Medtronic implantable cardiac pacemakers. In vitro testing consisted of: (1) unsynchronized pacemaker strapped on the patient with extracorporeal shock synchronized to the patient's native heart rate; and (2) pacemakers suspended alone in water 6 inches from the focal point, synchronizing the extracorporeal shock to pacemaker output. Unsynchronized shocks affected each model of pacemaker differently, i.e., single chamber constant rate pacemakers experienced extended periods of inhibition for more than three pacing cycles while activity-triggered rate response pacemakers exhibited rate increases to the upper rate setting. Dual chamber synchronous pacemakers exhibited intermittently a 59% decrease and a 20% increase in ventricular rate due to inhibition and triggering, respectively, from shock oversensing. Synchronized shocks did not alter the rate of single chamber constant rate pacemakers, but did cause the rate to increase to the upper rate setting for activity-triggered rate response pacemakers. The shock was synchronized to the initial atrial output from the dual chamber pacemaker and caused frequent inhibition of the ventricular stimulus when the ventricular-safety-pace (VSP) feature was programmed off. Programming VSP on reduced the incidence of ventricular inhibition resulting in near normal pacemaker operation. There was neither observable damage to pacemaker components nor spurious reprogramming of pacemaker parameters during the tests. Our studies with one manufacturer's pacemakers suggests that lithotripsy shock effects on implantable pacemakers can be tolerated provided: (1) the single chamber pacemaker is programmed to the demand constant rate modality; (2) the dual chamber pacemaker is programmed to VSP on or to the VVI mode; and (3) the pacemaker distance to the focal point is greater than 6 inches.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1988

Resolution of the intermediates of de novo purine biosynthesis by ion-pair reversed-phase high-performance liquid chromatography.

An ion-pair reversed-phase high-performance liquid chromotographic procedure capable of resolving twelve of the fourteen intermediates of de novo purine biosynthesis is presented. The method utilizes isocratic elution and detection by ultraviolet light absorption. Separation of all twelve intermediates can be achieved in 90 min.

Chromatography, High Pressure Liquid↗
PubMed1988

Isolation of DNA sequences on human chromosome 21 by application of a recombination-based assay to DNA from flow-sorted chromosomes.

By merging two efficient technologies, bivariate flow sorting of human metaphase chromosomes and a recombination-based assay for sequence complexity, we isolated 28 cloned DNA segments homologous to loci on human chromosome 21. Subregional mapping of these DNA segments with a somatic cell hybrid panel showed that 26 of the 28 cloned DNA sequences are distributed along the long arm of chromosome 21, while the other 2 hybridize with sequences on the short arm of both chromosome 21 and other chromosomes. This new collection of probes homologous to chromosome 21 should facilitate molecular analyses of trisomy 21 by providing DNA probes for the linkage map of chromosome 21, for studies of nondisjunction, for chromosome walking in clinically relevant subregions of chromosome 21, and for the isolation of genes on chromosome 21 following the screening of cDNA libraries.

Animals↗
PubMed1988

Mapping of bovine PRGS and PAIS genes in hybrid somatic cells: syntenic conservation with human chromosome 21.

Somatic cell genetics coupled with enzyme electrophoresis has facilitated the mapping of PRGS and PAIS genes in cattle. Individual cow-hamster hybrid cell lines established by fusion of mutant CHO cells, ade-C and ade-G, with cattle leukocytes required complementing bovine genes for PRGS and PAIS, respectively, when propogated on selective media. Homogenates of 12 PRGS+ hybrid clones and 12 PAIS+ hybrid clones retained the bovine electromorph of SOD1 while extensively segregating 14 biochemical markers of other cattle syntenic groups. Secondary cattle-hamster hybrid subclones which segregated bovine PRGS and PAIS in late passages on nonselective media concordantly segregated bovine SOD1. These data support a syntenic relationship among PRGS, PAIS, and SOD1 on cattle syntenic group U10. An interferon receptor locus, IFREC, is also syntenic with SOD1. This synteny represents an extensive conservation of bovine U10 and the "Down syndrome region" of human chromosome 21.

Animals↗
PubMed1988

Irradiation-reduced human chromosome 21 hybrids.

Rodent-human somatic cell hybrids have been constructed which contain fragments of human chromosome 21 as their only human material. This was done by irradiating rodent-human somatic cell hybrids containing a complete chromosome 21 to fragment the genome and then rescuing human GAR synthetase and various amounts of flanking chromosome 21 DNA by fusing with GAR synthetase-deficient hamster cells and selecting for growth in purine-free medium. Four irradiation-reduction hybrids were produced by this method and contain the distal, proximal, and central portions of the long arm of human chromosome 21, all centered about GAR synthetase. These irradiation-reduction hybrids were used as a panel to regionally map single-copy and individual copies of repetitive sequences. Using these hybrids along with another independently constructed hybrid, the GAR synthetase gene was mapped distal to SOD-1 and proximal to CP21G1(D21S60). Of special interest is the regional mapping of the gene for the amyloid beta-protein distal to pPW236B(D21S11) and proximal to SOD-1.

Animals↗
PubMed1988

Partial physical map of human chromosome 21.

The long arm of human chromosome 21 has been analyzed with unique sequence DNA probes, using an expanded panel of somatic cell hybrids containing defined regions of the chromosome, and both standard and pulsed field gel electrophoresis. Each member of the hybrid cell panel contains either a normal chromosome 21, or one of 11 different translocations or deletions within the long arm. Together, these now include 11 breakpoints, defining 11 long arm regions. Thirty-two unique sequence probes have been localized to these regions by standard gel electrophoresis. Analysis by pulsed field gels indicates that 27 of these identify a total of 18 Not1 restriction fragments, which together account for approximately 17 million base pairs, over half the long arm. Five physical linkage groups have been identified, as well as patterns in the distribution of unique sequences and GC-rich chromosomal regions. This information can be correlated with that obtained by other methods and contributes to the construction of a detailed physical map of this chromosome.

Chromosome Mapping↗
PubMed1988

The ETS genes on chromosome 21 are distal to the breakpoint of the acute myelogenous leukemia translocation (8;21).

The definition of the genetic linkage map of human chromosomes may be helpful in the analysis of cancer-specific chromosome abnormalities. In the translocation (8;21)(q22;q22), a nonrandom cytogenetic abnormality of acute myelogenous leukemia (AML), we previously observed the transposition of the ETS2 gene located at the 21q22 region from chromosome 21 to chromosome 8. However, no ETS2 rearrangements were detected in the DNA of t(8;21)-positive AML cells. Genetic linkage analysis has allowed us to locate the ETS2 gene relative to other loci and to establish that the breakpoint is at an approximate genetic distance of 17 cM from ETS2. When the information from the linkage map is combined with that from molecular studies, it is apparent that (a) the t(8;21) breakpoint does not affect the ETS2 gene structure or the structure of the other four loci proximal to ETS2: D21S55, D21S57, D21S17, and ERG, and ETS-related gene; and (b) the actual DNA sequence involved in the t(8;21) must reside in a 3-cM genetic region between the D21S58 and the D21S55/D21S57 loci, and remains to be identified.

Blotting, Northern↗
PubMed1988

Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21.

The gene encoding the beta-amyloid precursor protein has been assigned to human chromosome 21, as has a gene responsible for at least some cases of familial Alzheimer disease. Linkage studies strongly suggest that the beta-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers. The precise location of the beta-amyloid precursor protein gene on chromosome 21 has not yet been determined. Here we show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the beta-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.

Alzheimer Disease↗