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Biomedical subjects

R L Adams

Publications and source records attributed to R L Adams.

At least 73 records · Page 4Linked to original sources

Differential sensitivity of the WMS to the effects of IQ and brain damage.

The sensitivity of the Wechsler Memory Scale with Russell's Revision to the effects of IQ and brain damage was assessed in groups of brain-damaged (N = 64) and nonbrain-damaged (N = 64) subjects. Brain-damaged and nonbrain-damaged subjects were divided into subgroups equated on age and IQ for each of three IQ ranges (80-89, 90-99, 100-109). Some Wechsler Memory Scale subtests were affected only by IQ, others were affected by IQ and brain-damage status, and still others were affected only by brain-damage status. Measures of recall efficiency were most useful in discriminating brain-damaged and nonbrain-damaged subjects. We concluded that specific Wechsler Memory Scale subtests are useful in assessing memory deficits in brain-damaged patients.

Journal Article↗

DNA methylase from Pisum sativum.

DNA methylase activity was detected in nuclei from pea shoots. The enzyme can only be extracted by low-salt treatment if the nuclei are pretreated with micrococcal nuclease. Only a single enzyme was detected, and it was purified to a specific activity of 1620 units/mg of protein. It has an Mr of 160,000 on gel filtration and SDS/PAGE. Pea DNA methylase methylates cytosine in all four dinucleotides, and this is interpreted to show that it acts on CNG trinucleotides. Although it shows a strong preference for hemi-methylated double-stranded DNA, it is also capable of methylation de novo. Homologous DNA is the best natural substrate. In vitro the enzyme interacts with DNA to form a salt-resistant complex with DNA that is stable for at least 4 h.

Base Sequence↗

Kinetic aspects of Ki-67 antigen expression in a normal cell line.

Using a normal cell line derived from a human fetus, the disappearance and reappearance of the Ki-67-reactive antigen following modification of the cell cycle was observed and estimated immunohistologically. It was found that G1/G0 arrest induced by serum deprivation resulted in loss of the antigen in 24 h in all but a few (usually less than 10%) of cells. Return to normal medium and resumption of growth was accompanied by reappearance in 30 h. When entry into S-phase was prevented by desferrioxamine, reappearance of the antigen still occurred but only lasted for about 24 h. Inhibition of protein synthesis with cycloheximide also caused fading and eventual loss of immunostaining. In view of the ease with which this antigen becomes undetectable with cessation of protein synthesis and interruption of the cell cycle, we agree with those who advise caution in the use of Ki-67 to measure growth fraction in changeable cell populations such as tumours.

Blood↗

Microassay for DNA methyltransferase.

A microassay for DNA methylase is described which can detect activity in as few as 50 tissue culture cells. The cells are lysed and incubated for 2 h at 37 degrees C with 3 microCi high specific activity [3H]AdoMet and 0.5 microgram poly[d(I-C).d(I-C)] in a volume of 23 microliters. Ribonuclease is present during the assay and the product DNA is isolated by phenol extraction after protease digestion.

DNA Modification Methylases↗

Clinical validity of the Speech-Sounds Perception Test and the Seashore Rhythm Test.

The interpretive significance of the Speech-Sounds Perception Test (SSPT) and the Seashore Rhythm Test (SRT) was evaluated through literature review and empirical investigations. Subjects were 43 pseudoneurologic controls and 81 brain-damaged persons, divided into subgroups of subjects with left-hemisphere damage (n = 20), diffuse brain damage (n = 31), and right-hemisphere damage (n = 30). Our data indicate that the SSPT and SRT failed to discriminate left- and right-hemisphere damage. Furthermore, discriminant analyses demonstrated that these tests make no unique diagnostic contribution within the context of a neuropsychological battery. We question whether these tests should be routinely used.

Adolescent↗

Can flow cytometry reduce the workload for cervical screening? The results of a series of 622 specimens.

A simple method permitting the flow cytometric examination of cervical specimens has been developed and an assessment made of the feasibility of relying on this method to screen women for cervical neoplasia. Examination of four flow cytometric parameters showed differences between morphologically normal and abnormal specimens and allowed identification of a proportion of the normal specimens. The system had a false negative rate of 8%. Our experience with cervical specimens has revealed a number of problems associated with their examination by flow cytometry and these are discussed.

Evaluation Studies as Topic↗

Decrease in DNA methylase activity during preimplantation development in the mouse.

During early mouse development, there are large-scale changes in DNA methylation. These changes may be due to the availability or stability of the enzyme, DNA methyltransferase (methylase), which is responsible for maintenance of DNA methylation. A microassay for methylase activity in preimplantation embryos shows that the level of maternally inherited enzyme is extremely high in the egg and that this activity is stable for the first three cleavage divisions. However, from the 8-cell to the blastocyst stage, there is a marked and absolute decrease in enzyme activity.

Animals↗

Lateralized brain damage and performance on trail making A and B, Digit Span Forward and Backward, and TPT Memory and Location.

The present retrospective study was undertaken to determine whether Trail Making Test A and B, Digit Span Forward and Backward, and TPT Memory and Location scores are differentially sensitive to right or left hemisphere brain damage. Groups of patients with right, left, and generalized cerebral lesions and matched normal controls were compared. Results showed a relative failure for any individual measure, difference, or ratio score to reliably distinguish between right and left hemisphere lesions. Patients with diffuse lesions performed significantly worse than non-neurologic medical controls and right and left lesion groups on Trails A and TPT Memory and Location. Results are discussed in terms of specific methodological variables including chronicity of lesion, the nature of the task demands, and priming effects.

Journal Article↗

DNA demethylation in erythroleukaemia cells.

Despite a fall in the proportion of CGs methylated, evidence has not been obtained for significant demethylation of prelabelled DNA when mouse erythroleukaemia cells are induced to differentiate. There is, however, a delay in the methylation of the DNA that is synthesised in the early period of induction, leading to its undermethylation by 30-50% and this may be a contributory cause of the observed fall in CG methylation.

Animals↗

Eukaryotic DNA methylases and their use for in vitro methylation.

DNA methylases from mouse and pea have been purified and characterized. Both are high molecular mass enzymes that show greater activity with hemimethylated than unmethylated substrate DNA. Both methylate cytosines in CpG preferentially, but not exclusively and show similar kinetics of methylation, which makes it difficult to saturate all possible sites on the DNA, but procedures are described that circumvent this problem.

Animals↗

DNA methylation. The effect of minor bases on DNA-protein interactions.

DNA methylation is found almost ubiquitously in nature and the methyltransferases show evidence of a common evolutionary origin. It will be a fascinating study in protein evolution to follow the ways in which the structures of the various enzymes have developed. Although methylation may have a direct effect on DNA structure the evidence for the importance of this in vivo is accumulating only slowly. In contrast, there is now abundant evidence that methylation of DNA affects DNA-protein interactions and so may have a function in all processes in which such interactions occur. The binding of nucleases is affected in the processes of mismatch repair, DNA restriction and possibly demethylation during differentiation in vertebrates. The binding of transcription factors is affected by DNA methylation and the association of DNA with packaging and segregation proteins may play a part in the control of transcription and replication. The interplay of these effects makes DNA methylation a complex but rewarding area for study. Perhaps we should no longer refer to methylcytosine and methyladenine as minor bases, but rather as key bases which help regulate the functions of DNA.

DNA↗

Luria Memory Words Test and Wechsler Memory Scale: comparison of utility in discriminating neurologically impaired from controls.

Memory deficits are among the most common initial complaints of patients who are suffering from neurological disorders. The present study compared the relative clinical utility of the Wechsler Memory Scale and the Luria Memory Words Test in differentiating brain-damaged (N = 60) from non-brain-damaged patients (N = 60). Separate stepwise regression analyses selected five variables from each test that accounted for the greatest between-group variance. Separate discriminant functions then were computed that used the WMS and the Luria Words variables selected through the regression analyses. The WMS correctly classified 72% of the subjects, whereas the Luria Words correctly classified 76% of the subjects. A final discriminant function was computed that used all 10 variables and resulted in a classification accuracy of 86%, with 6% false positives and 6% false negatives. Results are discussed relative to the use of each instrument in both a general psychological assessment situation and when specific memory functioning is in question.

Brain Damage, Chronic↗

Methylation of hen erythrocyte DNA.

We have analysed the 5-methylcytosine content of hen erythrocyte DNA and found it to be lower than that of DNA from other chick tissues analysed. Erythrocyte DNA is also a better substrate for DNA methylase having a five-fold lower Km than DNA from white blood cells. This is probably because it contains a large number of hemimethylated sites. Thus the inverse correlation between methylation and gene expression does not apply to the chick red blood cell.

5-Methylcytosine↗

Til 1--a human lymphoblastoid cell line with minimal DNA methylation.

Methylation has been shown to be correlated with several fundamental cellular processes, including changes in gene expression, alterations in chromatin structure and inactivation of the mammalian X chromosome. It is possible, therefore, that the methylation status of a particular sequence may reflect involvement in a number of processes. Given this potentially confused situation, it is clear that many studies would be facilitated if unmethylated or minimally methylated DNA from a mammalian source were available. A major use of such DNA would be in the construction of long-range physical maps. In many cases, long-range physical maps are a prerequisite for the eventual isolation of disease genes that have been localised to a particular chromosomal region by other means (e.g. genetic linkage studies). Many of the enzymes used in such long-range mapping experiments are methylation sensitive, which makes it difficult to determine how many sites for a particular enzyme are present in any DNA sequence. Here we report the finding of a minimally methylated DNA in the human lymphoblastoid cell line, Til 1. The methylation level of Til 1 DNA was analysed in several ways and compared with that in human lymphocytes, placental tissue and other lymphoblastoid cell lines. The results showed clear and reproducible differences in methylation among the cell types, both at a global level and in the vicinities of specific DNA sequences. Lymphocyte DNA had the highest level of methylation while placental DNA and cell line DNA had lower but similar levels. Til 1 had abnormally low levels of 5-methylcytosine when measured directly, and no detectable methylation at any of the restriction sites examined.

5-Methylcytosine↗

Factor analysis of verbal and nonverbal clinical memory tests.

This study represents an attempt to evaluate the construct validity of various verbal and nonverbal clinical memory tests. Marker variables for verbal, visual-perceptual-motor and attention-concentration abilities were employed in order to demonstrate the relative independence of these abilities from the memory measures. Subjects were 119 individuals (aged 16-74) from a combined sample of brain damaged and non-neurologic medical controls. Principal components analyses with orthogonal varimax rotations produced four factors in both Immediate and Delayed analyses: nonverbal memory and visual-perceptual-motor skills, verbal learning and memory, general verbal abilities, and attention-concentration. The inclusion of additional nonverbal memory measures helped to create a modality specific nonverbal factor but did not produce a pure nonverbal memory factor. The Wechsler Memory Quotient had modest loadings on three of the four factors.

Journal Article↗

Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus.

Infection of rat embryo cells with herpes simplex virus type 2 caused undermethylation of host cell DNA synthesized during infection. DNA made prior to infection was not demethylated, but some of its degradation products, including methyl dCMP, were incorporated into viral DNA. The use of mutant virus showed that some viral DNA synthesis appears to be required for the inhibition of methylation. Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.

Animals↗

CpG deficiency, dinucleotide distributions and nucleosome positioning.

The dinucleotide CpG is deficient in (A + T)-rich regions of vertebrate DNA in both coding and non-coding sequences and there is a corresponding increase above expectation in the occurrence of TpG and CpA. By contrast in (G + C)-rich regions no deficiency of CpG is found. Such (G + C)-rich sequences, containing the expected number of CpG dinucleotides, alternate along the genome with (A + T)-rich sequences which have a lower than expected CpG content. The G + C content of vertebrate DNA can oscillate with a period of 150-200 bp and this may be a factor in positioning nucleosomes. The role of mutagenesis in loss of CpG and increase of A + T, particularly in non-coding regions, is discussed.

Base Composition↗