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Biomedical subjects

L Dickinson

Publications and source records attributed to L Dickinson.

At least 19 recordsLinked to original sources
PubMed2000

Development of a quality control material for the measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an in vivo marker of oxidative stress, and comparison of results from different laboratories.

The measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine is an increasingly popular marker of in vivo oxidative damage to DNA. A random-sequence 21-mer oligonucleotide 5'-TCA GXC GTA CGT GAT CTC AGT-3' in which X was 8-oxo-guanine (8-oxo-G) was purified and accurate determination of the oxidised base was confirmed by a 32P-end labelling strategy. The lyophilised material was analysed for its absolute content of 8-oxo-dG by several major laboratories in Europe and one in Japan. Most laboratories using HPLC-ECD underestimated, while GC-MS-SIM overestimated the level of the lesion. HPLC-ECD measured the target value with greatest accuracy. The results also suggest that none of the procedures can accurately quantitate levels of 1 in 10(6) 8-oxo-(d)G in DNA.

Biomarkers↗
PubMed1999

SVPD-post-labeling detection of oxidative damage negates the problem of adventitious oxidative effects during 32P-labeling.

The exploitation of oxidative DNA lesions as biomarkers of oxidative stress in vivo requires techniques that allow for the precise and valid measurement of oxidative damage to DNA. Previously, endogenous levels of the oxidative lesion 8-hydroxy-2'-deoxyguanosine (8-HO-dG) in rat tissues determined by a micrococcal nuclease/calf spleen phosphodiesterase-based 32P-post-labeling protocol were found to be at least 10-fold higher than those determined by HPLC with electrochemical detection. This was attributed to the adventitious oxidation of the normal nucleotides (dGp) occurring during the labeling stage of the postlabeling protocol, which could only be prevented by the introduction of additional chromatographic steps to remove the unmodified species prior to labeling. In the present study we report that an alternative snake venom phosphodiesterase-based 32P-post-labeling procedure (SVPD-postlabeling) negates the problem of adventitious oxidative damage during labeling by virtue of a unique digestion strategy. In SVPD-post-labeling, digestion yields certain lesions (thymine glycols, phosphoglycolates and abasic sites) as damage-containing dimer species which are ready substrates for labeling. In contrast, the undamaged DNA is recovered as mononucleoside species (dN) which are not substrates for labeling and so remain undetected. Furthermore, even if the mononucleosides are oxidized during labeling, they will not contribute to the level of damage detected. Indeed, we demonstrate that neither the external gamma-irradiation of the digested DNA samples nor increasing the incubation time of the labeling reaction alters the levels of damage detected by SVPD-post-labeling. The negation of adventitious oxidative effects during labeling deems that an optimized SVPD-post-labeling procedure should be well-suited for the biomonitoring of endogenous oxidative stress in vivo.

Animals↗
PubMed1992

Biological significance of unwinding capability of nuclear matrix-associating DNAs.

Matrix attachment regions (MARs) are thought to separate chromatin into topologically constrained loop domains. A MAR located 5' of the human beta-interferon gene becomes stably base-unpaired under superhelical strain, as do the MARs flanking the immunoglobulin heavy chain gene enhancer; in both cases a nucleation site exists for DNA unwinding. Concatemerized oligonucleotides containing the unwinding nucleation site exhibited a strong affinity for the nuclear scaffold and augmented SV40 promoter activity in stable transformants. Mutated concatemerized oligonucleotides resisted unwinding, showed weak affinity for the nuclear scaffold, and did not enhance promoter activity. These results suggest that the DNA feature capable of relieving superhelical strain is important for MAR functions.

Base Sequence↗
PubMed1988

A family of bacteria-regulated, cecropin D-like peptides from Manduca sexta.

Manduca sexta larvae respond to bacterial challenge by synthesizing a set of antibacterial hemolymph proteins. We have purified and sequenced three members of a family of cecropin D-like bactericidal peptides and isolated a cDNA clone complementary to a closely related bactericidin. Results obtained by Northern hybridization and RNase protection analysis showed that the increased synthesis of bactericidins is due to induction of their mRNA levels and that the synthesis of these peptides is not strictly tissue-specific, in contrast to previous beliefs. Although fat body was a richer source, the relative amounts of bactericidin mRNA were significant in seven other tissues examined.

Amino Acid Sequence↗
PubMed1985

Effect of simultaneously ingested milk on phenytoin bioavailability.

Adverse gastrointestinal symptoms from milk may reduce the bioavailability of phenytoin. In a prospective crossover study, we studied the effect of simultaneous ingestion of phenytoin and milk in 12 patients with partial epilepsy and no adverse gastrointestinal symptoms. Serum phenytoin levels were measured at the start of the study and after 2 weeks. Patients then switched regimens, and a third phenytoin level was determined 2 weeks later. Serum phenytoin levels were similar for patients taking phenytoin with either milk or water.

Adult↗
PubMed1983

Growth in children with acute lymphocytic leukemia: a Pediatric Oncology Group study.

We have studied 127 children from 5 participating institutions as to the effect of acute lymphoblastic leukemia (ALL) or the therapy used in the treatment of ALL on growth, growth hormone concentrations, and somatomedin activity. The study (SWOG No. 7581) was initiated in December 1975 and was closed to new entry in September 1979 and to data collection in February 1981. Heights, weights, and blood samples for growth hormone and somatomedin activity were obtained at the time of initial diagnosis and at intervals during the 55 months of observation. The percentage of boys less than 4 years of age below the 50th percentile is significantly greater than the expected 50% for both initial and final height (P less than 0.01). Girls less than 4 years appeared to have significantly different percentile height distribution from the normal for their final height measurement (P less than 0.05) but not for their initial height measurement. No other significant differences in the percentile height distribution were found. When growth rate, since time of diagnosis of ALL, is compared to the expected growth of normal children of the same age by linear regression analysis, there is a difference in the slope of the lines. Children with ALL are significantly shorter. The mean initial growth hormone and somatomedin concentration, 6.2 ng/ml and 1.3 micrograms/ml, respectively, vs mean remission growth hormone and somatomedin of 2.5 ng/ml and 1.1 micrograms/ml, respectively, were different. This was significant at P less than 0.01. The slope of the computed regression lines for multiple analysis of growth hormone and somatomedin were negative for more than 60% of the patients when compared to the initial concentration. These data suggest that a significant number of the children less than 4 years of age are short prior to the onset of therapy, and this persists throughout the course of their disease. Second, there is a reduction in growth rate during intensive therapy or the first year of the disease, with a normal growth rate thereafter. Third, growth hormone and somatomedin concentrations appear to be higher at the time of onset of the disease and decrease while on therapy.

Adolescent↗
PubMed1978

Differential effects of cranial radiation on growth hormone response to arginine and insulin infusion.

The growth hormone responses to arginine infusion and to insulin-induced hypoglycemia were studied in 13 patients with neoplastic disease after treatment with radiation and chemotherapy. Patients who received intensive cranial radiation (greater than 2,400 rads) had no response to either arginine or insulin; those who received moderate cranial radiation (greater than or equal to 2,400 rads) had GH response to arginine but not to insulin; patients receiving no cranial radiation responded to both arginine and insulin. These data support the hypothesis that GH secretion in response to arginine infusion has a different mechanism in contrast to the response to insulin-induced hypoglycemia and that the latter is more vulnerable to cranial radiation.

Adolescent↗