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Biomedical subjects

S Dooley

Publications and source records attributed to S Dooley.

At least 55 records · Page 3Linked to original sources
PubMed1993

A case-control study of driving-while-impaired offenders.

A case control approach was used to identify variables associated with driving while impaired (DWI). Data utilized for this study were obtained from interviews with individuals in a representative sample of 9943 Canadians. Individuals convicted for DWI were matched with control subjects (i.e. no DWI convictions) by gender, age, province of residence, education, income, and recent drinking behaviour. During the matching process, 39 current abstainers were found among the DWI offenders and were treated as a separate group for statistical purposes. Three groups were compared: 78 DWI cases, 78 matched controls, and 39 DWI current abstainers. Statistical analyses were used to detect significant differences among these three groups for 81 variables within the following categories: (a) attitudes, knowledge and behaviour related to drinking and driving; (b) driving behaviour; (c) drinking behaviour and drug use; (d) social issues; and (e) attitudes towards different policy approaches to reducing drinking and driving. DWI cases were significantly different from control subjects for only 10 variables. A high proportion of differences found between these two groups related to attitudes regarding drinking and driving behaviour. For example, DWI cases were more likely than controls to believe that some people drive better after drinking, that it takes more alcohol to be legally impaired, and that there is an excuse for DWI. DWI cases were more likely to drink due to sadness or loneliness, and reported higher cannabis use over previous years. Little evidence was found to support the hypothesis that DWI offenders are less likely to perceive deterrents to DWI. However, evidence does support the notion that many DWI offenders do not believe that they have a drinking problem. Implications of the findings are discussed.

Adolescent↗
PubMed1992

DNA-protein interaction analysis using polyacrylamide gel electrophoresis and a simple and sensitive UV crosslinking procedure.

A simple and reproducible technique for DNA-protein interaction analysis is described using UV crosslinking and polyacrylamide gel electrophoresis, leading to visualization of the complexes as distinct and strong signals. It avoids incorporation of bromodeoxyuridine (BrdU) into DNA and requires no special equipment. It was successfully applied to an oligonucleotide sequence from within the first intron of the mouse myb proto-oncogene and nuclear extracts from a myb-expressing cell line.

Base Sequence↗
PubMed1992

A non-alphoid repetitive DNA sequence from human chromosome 21.

A non-alphoid repetitive DNA from human chromosome 22, consisting of a 48-bp motif, shows homology to both G-group chromosomes in the gorilla, thus indicating the presence of additional repeat family members on further human chromosomes. Therefore, we screened a chromosome-21-specific cosmid library using this repetitive sequence from chromosome 22 (D22Z3). Some 40-50 cosmid clones were positive in tests for hybridization. One of the clones giving the strongest signals was digested with EcoRI/PstI, which we knew to cut frequently within the repeats; this resulted in fragments containing repeat units only. The fragments were subcloned into plasmid vector pTZ 19. Sequence-analysis of a 500-bp insert showed ten copies of a 48-bp repeat similar to D22Z3, with about 15% sequence deviation from the chromosome 22 consensus sequence. In situ hybridization of the newly isolated recombinant established its chromosome 21 specificity at high stringency. Physical mapping by pulsed field gel electrophoresis placed this new repeat in close vicinity to the chromosome 21 alphoid repeat. No cross-hybridization with other mammalian genomes except for those of apes was observed. The locus has been designated D21Z2 by the Genome Data Base. A gel mobility shift assay indicated that this repetitive motif has protein-binding properties.

Animals↗
PubMed1992

Nonradioactive southwestern analysis using chemiluminescent detection.

Replacing radioactively labeled probes by nonradioactive ones and detection by chemiluminescence instead of colorimetry allows a nonhazardous handling and offers the possibility of easily reprobing filters in Southwestern analysis. Using the described procedure, we were able to determine the molecular weight of DNA-binding proteins and achieve a high signal-to-noise ratio.

Animals↗
PubMed1991

A set of 4 nuclear proteins binds to a DNA sequence within the FOS promoter region.

We investigated DNA-protein-interactions occurring in the promoter region of c-fos using two-dimensional electrophoresis and south-western-blotting. When nuclear extracts from the human glioblastoma cell line HeRoSV were tested for their DNA-binding behaviour to a 650 bp-fragment within the promoter region of c-fos, we found 4 proteins designated as 120/6.6, 75/5.4, 65/6.4 55/5.0 interacting with this fragment. An additional protein 60/6.0 was detected by using a digoxygenine-labelled probe. These observations let us to assume that beside the well characterized SRF and FOS-JUN proteins additional factors recognize the promoter sequence and may play a role in c-fos regulation.

Base Sequence↗
PubMed1990

Generating highly labeled oligonucleotides for DNA-protein interaction.

We developed a new strategy to prepare double-stranded oligonucleotides containing recognition sites for specific binding proteins to examine DNA-protein interactions in various assays (gel mobility shift, UV-crosslinking, and affinity chromatography). The advantages of our procedures are as follows. Only one strand needs to be synthesized using a commercial oligonucleotide synthesizer. The probes can be labeled to a high specific activity and the exact position of labeling can be chosen, which is necessary for UV-crosslinking studies. Furthermore, multimeric binding sites for efficient DNA affinity chromatography can easily be generated. It is also possible to precisely place modified bases without the need for chemical precursors. Using this protocol, more detailed information about the binding protein factors and their behavior in interaction with recognition sites can be obtained.

Base Sequence↗
PubMed1989

A rapid protocol for the purification of mitochondrial DNA suitable for studying restriction fragment length polymorphisms.

When analyzing mitochondrial DNA (mtDNA) from various normal and malignant human tissues, it became necessary to enhance mtDNA isolation for improved yields and quality. The method described here consists of rapid and simple-to-perform steps, avoiding complicated instrumentation. It was designed for preparation of undegraded mtDNA and is highly useful when limited amounts of tissues, cells and unique biopsies of tumors (fresh or frozen) are available. The resulting mtDNA is sufficiently pure for restriction analysis, subcloning, labeling and various types of hybridization. Using Sau3A and MspI, restriction analysis revealed new restriction-fragment length polymorphisms for Caucasians, independent of the DNA source, and hence excluding tissue-specific DNA modifications.

Centrifugation↗
PubMed1989

DNA curvature in front of the human mitochondrial L-strand replication origin with specific protein binding.

DNA bending has been suggested to play a role in the regulation of gene expression, initiation of DNA-replication, site specific recombination, and DNA packaging. In the human mitochondrial DNA we have found a DNA curvature structure within the 3'-region of ther URF2 sequence in front of the L-strand origin of replication. This structure interacts specifically with a protein factor isolated from mitochondria. Based on the localization of this DNA curvature structure and the known function of such structures the data suggest a model in which this DNA signal sequence and its specific protein binding is involved in the regulatory initiation event of L-strand replication.

Base Sequence↗
PubMed1989

Increased risk for gestational diabetes mellitus associated with insulin receptor and insulin-like growth factor II restriction fragment length polymorphisms.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. We have examined restriction fragment length polymorphisms (RFLPs) near "candidate diabetogenic genes" as one approach to identify molecular markers for GDM genes. Genotypes for insulin hypervariable region (HVR), insulin-like growth factor II (IGF2), insulin receptor (INSR), and glucose transporter (GLUT1) RFLPs were studied in 96 GDM and 164 control subjects, matched to GDM for race, age, and gravidity. Logistic regression analysis was used to explore the relationship between genotypes at these candidate gene loci and GDM, while adjusting for the effects of potential confounding variables. Among black subjects, the INSR allele 1 (P = 0.001) and interactions between INSR allele 1 with body mass index (BMI) (P = 0.002) and history of DM in subject's mother (P = 0.004) contributed significantly to GDM risk. Among Caucasian subjects, a similar relationship between the INSR allele 1 (P = 0.007) and INSR allele 1-BMI interactions (P = 0.011) on GDM risk were observed. In Caucasians, an additional significant risk factor was determined by an INSR allele 1-IGF2 allele 2 interaction (P = 0.018). No risk factors were identified in Hispanic subjects. These data continue to support the hypothesis that GDM is a heterogeneous disorder with respect to phenotypic and genotypic features. Furthermore, our data suggest that risk for GDM in black and Caucasian subjects is not due to obesity perse but to interactions between obesity and INSR alleles. In Caucasian women, INSR and IGF2 alleles interact to confer additional risk for GDM. Thus genes underlying susceptibility to GDM in some women may be similar to genes conferring risk to NIDDM, while in others novel genes may contribute to GDM risk.

Chromosome Mapping↗
PubMed1989

Chronic exposure to carbon monoxide at high altitude: effects on mean electrical axis.

The effects of breathing CO continuously at high altitude on the mean electrical axis of the heart, hematocrit ratio and body weight were studied in laboratory rats. Laboratory rats were exposed for 6 weeks to: 100 or 500 ppm CO; 15,000 feet stimulated high altitude (SHA); or 100 or 500 ppm CO at SHA. SHA decreased body weight significantly; CO and CO-SHA interaction had no significant effect on body weight. CO and SHA increased hematocrit ratio significantly; five hundred ppm CO increased hematocrit ratio to a greater extent than 100 ppm CO. There was a significant interaction between 500 ppm CO and SHA on hematocrit ratio. The mean electrical axis (MEA) was shifted to the right by SHA, and shifted to the left by CO. The effect was dose dependent, with the greater left shift occurring with 500 ppm CO. There was a significant interaction between 500 ppm CO and SHA on the MEA. These results indicate that, in general, the effects produced by 15,000 feet SHA are not intensified by 100 ppm CO, but are intensified by 500 ppm CO.

Altitude Sickness↗
PubMed1987

Restriction fragment length polymorphisms of the insulin gene hypervariable region in gestational onset diabetes mellitus.

Restriction fragment length polymorphisms in the insulin gene hypervariable region are compared among 93 women with gestational onset diabetes mellitus and 146 women with normal glucose tolerance during pregnancy. No significant differences in gene or genotype frequencies were observed in the overall sample (p greater than 0.50). However, an increased frequency of one allele (class 1) was observed among nonoverweight patients with gestational onset diabetes mellitus with elevated fasting plasma glucose levels compared with age-, race-, and parity-matched control subjects (p = 0.061). These data suggest that gestational onset diabetes mellitus is a heterogeneous disorder with respect to both genotypic and phenotypic characteristics, and that restriction fragment length polymorphisms near the insulin gene may serve as a molecular marker for susceptibility to gestational onset diabetes mellitus only in some women.

Alleles↗