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Biomedical subjects

J C Norton

Publications and source records attributed to J C Norton.

At least 19 recordsLinked to original sources
PubMed1998

Enhanced detection of human telomerase activity.

The detectability of telomerase activity in human cells almost always correlates with indefinite proliferation capability (immortalization). To make quantitative statements about telomerase activity levels, complete extraction of the telomerase activity is needed. A series of detergents was tested for this purpose, and a combination of NP-40 and sodium deoxycholate (NaDOC) was found to be the most efficient for extracting telomerase activity. Tumor-derived cell lines originally thought to contain differing amounts of telomerase on the basis of the original CHAPS bases extraction procedures have nearly equivalent amounts of activity when extracted with the NP-40/NaDOC lysis buffer. These results indicate that these lysis conditions can be used to extract telomerase activity more efficiently from tumor-derived cell lines.

Biochemistry↗
PubMed1996

Inhibition of human telomerase activity by peptide nucleic acids.

We report the inhibition of human telomerase activity by peptide nucleic acids (PNAs). PNAs recognize the RNA component of human telomerase (hTR) and inhibit activity of the enzyme with IC50 values in the picomolar to nanomolar range. Inhibition depends on targeting exact functional boundaries of the hTR template and is 10- to 50-fold more efficient than inhibition by analogous phosphorothioate (PS) oligomers. In contrast to high selectivity of inhibition by PNAs, PS oligomers inhibit telomerase in a non-sequence-selective fashion. These results demonstrate that PNAs can control the enzymatic activity of ribonucleoproteins and possess important advantages relative to PS oligomers in both the affinity and the specificity of their recognition. These observations should facilitate the development of effective inhibitors of telomerase activity and affinity probes of telomerase structure.

Base Sequence↗
PubMed1996

Enhancement of strand invasion by oligonucleotides through manipulation of backbone charge.

The ability of DNA oligonucleotides, neutral peptide nucleic acids (PNAS), and oligonucleotide conjugates to hybridize to inverted repeat sequences within supercoiled double-stranded DNA by Watson-Crick base-pairing is examined. PNAs and oligonucleotide conjugates initiate and maintain strand invasion under more stringent conditions than do unmodified DNA oligonucleotides. PNAs hybridize rapidly and, once bound, hold open a target site allowing oligonucleotides to base-pair to the displaced strand under conditions that would otherwise preclude hybridization. The ability to manipulate hybridization efficiency through different options for the alteration of oligomer charge should have important implications for optimizing sequence-specific recognition of DNA.

Amino Acid Sequence↗
PubMed1995

Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II.

Retinal degeneration slow (rds) is a semidominant mutation of mice that causes dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the human ortholog of the rds gene, are responsible for several inherited retinal dystrophies including a subset of retinitis pigmentosa. The normal rds locus encodes rds/peripherin, an integral membrane glycoprotein present in outer segment discs. Genomic libraries from wildtype and rds/rds mice were screened with an rds cDNA, and phage lambda clones that span the normal and mutant loci were mapped. We show that in mice, rds is caused by the insertion into exon II of a 9.2-kb repetitive genomic element that is very similar to the t haplotype-specific element in the H-2 complex. The entire element is included in the RNA products of the mutant locus. We present evidence that rds in mice represents a null allele.

Alleles↗
PubMed1995

Accelerated hybridization of oligonucleotides to duplex DNA.

We report two strategies for accelerating the hybridization of oligonucleotides to DNA. We demonstrate that oligodeoxyribonucleotides and peptide nucleic acid oligomers hybridize to inverted repeats within duplex DNA by D-loop formation. Oligonucleotides and duplex template form an active complex, which can be recognized by T7 DNA polymerase to prime polymerization. Quantitation of polymerization products allowed the rate of hybridization to be estimated, and peptide nucleic acid oligomers and oligonucleotide-protein adducts anneal with association constants 500- and 12,000-fold greater, respectively, than the analogous unmodified oligonucleotides. Together, these results indicate that sequences within duplex DNA can be targeted by Watson-Crick base pairing and that chemical modifications can dramatically enhance the rate of strand association. These findings should facilitate targeting of oligomers for priming DNA polymerization, the detection of diagnostic sequences, and the disruption of gene expression. The observed acceleration of hybridization may offer a new perspective on the ability of RecA or other proteins to accelerate strand invasion.

Base Sequence↗
PubMed1995

Targeting peptide nucleic acid-protein conjugates to structural features within duplex DNA.

A convenient small scale synthesis has been developed for obtaining peptide nucleic acid oligomers (PNAs). PNAs have been conjugated to a protein, staphylococcal nuclease, through disulfide exchange between a cysteine at the 3'-(carboxy) end of the PNA and an introduced cysteine on the surface of the nuclease. Site specific DNA cleavage by the attached nuclease has been used to examine the Watson-Crick hybridization of the PNAs to duplex DNA. Substantial affinity cleavage occurred when target sites contained inverted repeats which have the potential to form non B-DNA structures such as cruciforms. No affinity cleavage was observed at a site lacking apparent potential for non B-DNA structures. These results indicate that the Watson-Crick hybridization of PNAs to duplex DNA by strand displacement is favored by the presence of potential alternative secondary structures within the target sequence.

Base Sequence↗
PubMed1994

To stay or not to stay: issues in rural primary care physician retention in eastern Kentucky.

An important aspect of primary care physician availability is the retention of physicians once they have located. While retention has been under-researched compared to recruitment, it is especially important in rural areas where physician shortages already exist. This study reports the results of a retention survey completed by 132 primary care physicians in rural eastern Kentucky. The survey sets up an objective, hypothetical retention scenario and asks physicians to respond to structured questions and to an open-ended question about factors not appearing in the survey. In response to the structured portion of the survey, physicians indicate that relief coverage is the most important factor in rural physician retention. A content analysis of 75 open-ended responses reveals that besides the other factors in the survey, "sociocultural integration" is the pre-eminent retention issue for rural practitioners. This article concludes that the role of the local rural community may be more important in retention than in recruitment. Finally, it is suggested that additional in-depth qualitative research be conducted within the local contexts to enhance the understanding of rural physician retention processes.

Attitude of Health Personnel↗
PubMed1983

Psychomotor skills and technical ability in dental school.

Graduating dental students were grouped according to technical ability and compared with regard to admissions variables and a variety of psychomotor skills. Neither class of variable differentiated the groups. This article discusses implications for efforts to identify technically marginal students.

Clinical Competence↗
PubMed1979

Wechsler variables as a function of age and neurologic status.

Scores on Wechsler variables were analyzed in groups of patients broken down by age and neurologic status. No differences as a function of age were found in intelligence or memory. Timed Performance subtest results were related to age, but apparent Verbal subtest age differences were eliminated by the introduction of education as a covariate. Neurologic status showed significant effects on intelligence and memory and on all but 3 Wechsler subtests. No significant interactions between age and neurologic status were seen.

Adult↗
PubMed1978

The Trail Making Test and Bender Background Interference Procedure as screening devices.

The Trail Making Test and Bender Background Interference Procedure were evaluated with 598 Ss against both external neurologic criteria and against psychological opinion derived from a more complete evaluation. For Trails, highly significant differences in mean scores were seen when preselected neurologic patients and patients without neurologic stigmata were compared. Similarly, the distribution of classification of these patients by Bender is significantly different from chance. Application of these measures in a screening paradigm, however, yielded large numbers of false negatives against both neurological and psychological criteria. It was not possible to establish an optimal cutting score to justify application of these measures as screening devices, either alone or in concert.

Adult↗
PubMed1978

Medical problems of the alcoholic in nonmedical treatment.

The ambivalence about chronic alcohol abuse among health and related professionals can result in their failure to appreciate medical complications frequently associated with this disorder. Data from 81 male alcoholics are presented in this article to illustrate their increased risk of physical illness and premature death. The authors point to the need for more effective screening and monitoring procedures in alcoholism programs as well as improved training of professionals.

Adult↗
PubMed1977

A programmed training technique that uses reinforcement to facilitate acquisition and retention in brain-damaged patients.

Hospitalized brain-damaged patients were Ss in a study designed to evaluate the effectiveness of a treatment technique used with contingent reinforcement to facilitate acquisition and retention of environmentally relevant information. Ss were divided into three groups that were equated diagnostically and demographically. Group I received the treatment technique with contingent material and verbal reinforcement. Group II received the treatment technique with only contingent verbal reinforcement, and Group III was a control. Both treatment groups showed significant acquisition of the experimental information, and 1 week after training the two treatment groups showed no significant loss of acquired information. None of the groups showed any significant change in ward behavior during the experiment. It was concluded that the treatment technique used with contingent reinforcement can be used in the retraining of memory in brain-damaged patients.

Achievement↗