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Biomedical subjects

C O Anderson

Publications and source records attributed to C O Anderson.

14 recordsLinked to original sources
PubMed2000

Interactions of proteins in aqueous electrolyte solutions from fluorescence anisotropy and circular-dichroism measurements.

Understanding aqueous protein-protein interactions is crucial for the development of a molecular-thermodynamic model for salt-induced protein precipitation. In addition, protein interactions are important in many disease states, including cataract formation and alpha-amyloid diseases. Fluorescence anisotropy provides a means to measure intermolecular interactions. In this work, monomer-dimer equilibrium of the peptide T4 LYS(11-36) was studied by fluorescence anisotropy over the pH range 4-7 and the NaCl concentration range 0.0-1.0 M, in a 25 mM sodium phosphate buffer. This 26 amino-acid peptide is derived from the beta-sheet region of the T4 lysozyme molecule and has the potential to form amyloid fibrils. The association constant for dimerization increases with rising pH and ionic strength. The potential of mean force for peptide-peptide interactions was calculated from these association constants. Circular-dichroism measurements show that the peptide becomes more structured as the pH rises, possibly contributing to increased association.

Amino Acid Sequence↗
PubMed1986

Predominant role for DNA damage in etoposide-induced cytotoxicity and cell cycle perturbation in human SV40-transformed fibroblasts.

The cytotoxic and cell kinetic effects of the epipodophyllotoxin 4,6-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyr anoside) (VP-16) in cultured mammalian cells are thought to relate to the induction of DNA damage, specifically DNA strand interruptions. In an effort to explore this relationship in human cells we have identified a VP-16-hypersensitive human cell system, namely an SV40-transformed fibroblast line (AT5BIVA) originally derived from an ataxia telangiectasia (AT) patient. Evidence is presented that enhanced VP-16 sensitivity may be a consistent in vitro feature at AT derived cells. However, the intrinsic sensitivity (DNA strand breaks per lethal hit quantitated by nucleoid sedimentation) was the same for AT5BIVA and a corresponding normal control, indicating that the AT cell line accumulated more drug-induced DNA damage during short-term VP-16 exposures. It is suggested that AT cells may have abnormal topoisomerase II activity. The cell cycle responses of normal and AT cells to VP-16 exposure were complex, with the generation of parasynchronous S phase populations and the accumulation of cells in G2. Differences in cell killing or DNA strand breakage between normal and AT cells could only be correlated with the magnitude and kinetics of the G2 retention phenomenon. In short, there are several similarities in the action of ionizing radiation and VP-16. We suggest that the sensitivity of cellular DNA to VP-16-induced DNA damage and the kinetics of the G2 delay may be useful parameters for predicting the survival probability of drug-treated human tumor populations.

Ataxia Telangiectasia↗
PubMed1985

Effects of X-irradiation and sodium butyrate on cell-cycle traverse on normal and radiosensitive lymphoblastoid cells.

We have used a multi-parameter flow-cytometric technique to analyse changes in cell-cycle phase distribution (early and late G1, S and G2+M phases) for normal and X-ray-sensitive (ataxia-telangiectasia, A-T) lymphoblastoid cells exposed to X-irradiation and sodium butyrate (either alone or in combination). Sodium butyrate, an inhibitor of histone deacetylase, is a useful pharmacological tool for determining the proposed role of a histone acetylation-based chromatin surveillance system in controlling cell-cycle responses to DNA damage. We report that X-irradiated A-T cells (acute doses up to 1.5 Gy) demonstrate deficiencies in the capacity to traverse G1 and G2+M phases, although we can find no evidence of the specific involvement of a sodium butyrate-sensitive process in normal cells or abnormalities in the responses of A-T cells to the drug. We conclude that abnormal cellular control of G1 transition in A-T may be the basis of disturbed cellular differentiation in vivo, particularly in non-proliferating tissues under conditions of accumulated environmental or spontaneous DNA damage.

Ataxia Telangiectasia↗
PubMed1985

Abnormal retention of X-irradiated ataxia-telangiectasia fibroblasts in G2 phase of the cell cycle: cellular RNA content, chromatin stability and the effects of 3-aminobenzamide.

We have addressed three aspects of the abnormal sensitivity of SV40 transformed ataxia-telangiectasia (A-T) fibroblasts to X-irradiation, namely: (a) the radiogenic perturbations in cell-cycle traverse analysed by flow cytometry; (b) the involvement of 3-aminobenzamide-sensitive processes in cellular recovery in terms of viability and release from G2 + M phase delay; and (c) the functional and structural integrity of cells delayed in G2 + M phase using acridine orange as a probe for cellular RNA content and chromatin structure. We report that A-T cells show a dose-dependent and survival-related abnormal retention in G2 + M phase due to the lack of a recovery process, despite the capacity of such cells to synthesize ribosomal RNA and maintain the structural integrity of chromatin. Evidence is presented that the recovery process is dependent upon poly(ADP ribosyl)ation activity in both normal and A-T cells except that in the latter cell type recovery potential is rapidly saturated in terms of X-ray dose.

Ataxia Telangiectasia↗
PubMed1984

Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative.

A comparison was made of the ability of either X-radiation or a DNA-specific ligand (the vital bis-benzimidazole dye; Hoechst 33342) to induce: cell killing, inhibition of de novo DNA synthesis, DNA strand breakage and the delay of cell division in human colon adenocarcinoma cells in vitro. Unlike radiation-induced cell killing, ligand-induced cytotoxicity appeared to be positively correlated with the extent of inhibition of de novo DNA synthesis--a feature consistent with the persistent binding of ligand molecules to nuclear DNA. Ligand-induced DNA strand-breaks disappeared slowly although ligand-treated cells retained apparently normal capacities to repair discrete radiogenic DNA strand-breaks. Pre-treatment of cells with Hoechst 33342 resulted in a dose-modifying enhancement of radiation resistance not associated with altered dosimetry for strand-break induction. However, radioresistance was accompanied by the protracted retention of cells in the G2 phase of the cell cycle. We suggest that the results provide direct evidence that the retention of cells in G2 phase is a sparing phenomenon and is triggered by the responses of chromatin domains to the presence of DNA damage. Our results have implications for the use of DNA-interactive agents in combined modalities for tumour therapy, and indicate a possible basis for the sparing of some tumour cells in dividing populations.

Adenocarcinoma↗
PubMed1980

Ontogeny of the adrenal and behavioral responses of lambs to emotional stress.

The ontogeny of adrenocortical responsiveness in lambs was studied from 24 hr of age to maturity. Throughout the neonatal period, the adrenal axis was responsive to exogenous ACTH and the stresses of both restraint and exposure to open field testing. Newborn lambs both had higher resting levels of plasma corticosteroids and responded to the test stimuli with greater increases in corticosteroids than did other age groups. From the second week of life, the responsiveness of the adrenal axis was comparable to that of mature ewes. On exposure to an open field arena, lambs vocalized less and initiated movement sooner with increasing age and experience through 35 days of age, after which there was little change. Once locomotion was initiated, there was little difference in the amount of time spent moving in the arena. Open field testing was as potent a stimulator of the adrenal axis as restraint stress or exogenous ACTH.

Adrenal Glands↗
PubMed1978

Competitive social strategies in groups of deprived and experienced rhesus monkeys.

Behavior during competition for water was observed in 2 social groups of young rhesus monkeys (3 females, 3 males in each). Monkeys in one group were socially deprived and those in the other were socially experienced (raised with mother and agemates). Social status, based on dyadic recording of displacements at the water bottle, was predictive of a number of measures related to water consumption and social orientation in both groups, but this measure was less reliable and predictive for the experienced group than for the deprived groups, but this measure was less reliable and predictive for the experienced group than for the deprived group. A major reason for the comparatively low predictive value and reliability of status among experienced monkeys was their ability to influence the behavior of higher status members through responses directed to a 3rd party and other elaborate social strategies, many of which depended on responding to status relations between 2nd and 3rd parties. The fact that such strategies were only observed in the experienced group is a clear indication that the development of higher orders of social cognition is dependent on early social experience.

Animals↗
PubMed1978

Contrasting effects of living in heterosexual pairs and mixed groups on the structure of social attraction in squirrel monkeys (Saimiri).

The structure of social attraction was assessed in pair- and group-living squirrel monkeys (Saimiri) using paired-comparison and single-stimulus preference tests. Effects of the social environment were most prominent in females. Females housed with a single male showed sharply increased attraction to like-sex strangers and less pronounced increase in attraction to opposite-sex strangers, as compared to group-living females. Differences between pair- and group-living males were in the same direction found with females, but less extreme. Most group-living monkeys strongly preferred familiar animals to strangers regardless of sex, and like-sex to opposite-sex familiars. Change in the structure of social attractions in response to variations in the composition of the social environment appears to be an important factor in the maintenance of the species-typical grouping pattern in the squirrel monkey.

Animals↗
PubMed1977

Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys.

The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys.

Age Factors↗
PubMed1965

Rabbit: frequency of suckling in the pup.

Rabbit does were given free access to their young, access once a day, and access twice a day. In all three groups the young were nursed only once every 24 hours. Growth curves for the pups from day 2 of age to day 30 were identical for all three groups. The restriction of suckling to once a day appears to depend on the mother and not the pups.

Animals↗