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Biomedical subjects

P A Riley

Publications and source records attributed to P A Riley.

13 recordsLinked to original sources
PubMed1979

On the role of calcium in adhesion of cells to solid substrates.

Experiments are described which show that while the presence of calcium in the medium is required for the cells to maintain their adhesion, it is not necessary for the initial attachment of 3T3 cells to solid substrates. Cells are detached by treatment with urea at 4 degrees C suggesting that adhesion may involve hydrogen bonding between the cell surface and the substratum. Although most of the cell-bound calcium is removed by trypsin, the detaching effect of trypsinisation can be inhibited at low temperature suggesting that ionic calcium bridges are probably not directly involved in retaining the cells on the surface. Cells are made totally insensitive to removal by trypsin by prior washing with lanthanum. Our findings suggest that the external role of calcium in cell adhesion is exerted indirectly. We conclude that the cell presents to the exterior at least two physiochemical classes of molecule. One class composed of hydrogen bond-forming adhesive material (possible proteins) and another class of anti-adhesive molecules (possibly glycoproteins). These two components are somehow separated in the formation of adhesive 'plaques' and this process is process is apparently uninfluenced by the calcium concentration in the medium. However, the maintenance of the localised zones of adhesion is aided by factors which prevent their disruption by the intrusion into them of anti-adhesive molecules diffusing from adjacent regions of the cell membrane. These factors include cooling below the transition temperature of the membrane lipids and lateral cross-linking of non-adhesive elements by calcium. By contrast, conditions which reduce the stability of the separation of adhesive and non-adhesive surface components would be expected to diminish the overall adhesiveness of cells to the substratum.

Animals↗
PubMed1979

Time dependency of a critical effect of EGTA on DNA synthesis in cultures of Swiss 3T3 cells.

In a temporal analysis of the mitogenic response to serum, a critical period has been demonstrated just prior to the onset of replicative DNA synthesis during which transient calcium depletion blocks the subsequent entry of the cells into the S phase of the mitotic cycle. Transient washington of monolayer cultures of 3T3 cells with 2.5 mM EGTA between 6 and 8 h after serum-stimulated initiation of DNA synthesis was found to reduce cell-associated calcium levels and to inhibit thymidine incorporation, whereas similar treatment before (1-5 h) and after (8-9 h) had no detectable effect on either of these parameters when estimated after 21 h incubation. The effects during the chelation-sensitive period were reversed by the subsequent addition of fresh serum.

Animals↗
PubMed1978

Studies of long-range density effects on the proliferation of 3T3 and RLCW cells in recirculated medium.

Swiss mouse 3T3 cells and rat liver-derived RLCW cells were grown in monolayers and perfused with culture medium. A flow-rate dependent increase in the growth rate was observed both by 3H-thymidine uptake and by a rise in cell numbers. The characteristics of the response were dependent on the recirculating volume and on whether serum was present in the culture medium. In RLC cultures perfused with serum-supplemented medium the growth promoting effect decreased with increasing density of the cells. In the absence of serum, recirculation of NCTC medium had no effect on RLCs but increased growth was observed in recirculated MEM. In 3T3 cultures, a linear response was observed over a limited density range in the presence of 10% serum-supplemented medium indicating that substances present in the serum substantially modify the behaviour of the monolayer to perfusion. In serum-free medium the effect of perfusion on 3T3 cultures was confined to a small density range and was consistent with the more rapid removal of a diffusible inhibitor from the pericellular environment by recirculating the medium. Treatment of the perfusing medium with immobilised proteinases (trypsin, chymotrypsin, protease) did not alter the response except in the presence of putrescine.

Cell Count↗
PubMed1978

The degradation of normal and analogue-containing proteins in MRC-5 fibroblasts.

Proteins containing the arginine analogue canavanine were degraded much more quickly in MRC-5 fibroblasts than those containing only normal amino acids. The degradation of both classes of protein could be well described by a pair of exponential curves, the first representing an early rapid degradation and the second, a slower phase. There were no general trends in the variation with passage number of the cells' ability to degrade either normal or analogue-containing proteins, as judged by the half-lives of proteins. But there was an increase in the proportion of labelled normal protein falling into the early rapid degradation phase as the cells senesced in culture.

Canavanine↗
PubMed1978

Clinically significant adverse effects in a Phase 1 testing program.

Twelve years' experience with a Phase I drug testing program in normal prison volunteers is reported. Involved in 805 protocol studies were 29,162 participants over 614,534 subject days. During this period there were 64 significant medical events of which 58 were adverse drug reactions and 6 were complications. One subject has residual hip changes due to an infectious complication, another on placebo died from cerebrovascular hemorrhage while asleep. There was complete recovery from all adverse drug reactions and the other 4 complications encountered. Thus a clinically significant medical event occurred once every 9,602 days subject exposure or about once every 26.3 years of individual subject participation.

Drug Evaluation↗
PubMed1978

Phagocytosis of latex particles in relation to the cell cycle in 3T3 cells.

Cultures of 3T3 cells, synchronised by serum deprivation, were shown to phagocytose latex beads of 0.81 micrometer diameter more avidly in the G1 phase of the cell cycle. The maximum rate of about 0.12 particles/cell/hour was recorded 12 h after stimulation with 10% fetal bovine serum. After 24 h, when mitosis was beginning, the uptake fell to just above the unstimulated level of 0.06 particles/cell/hour. Exocytosis was linear and only 7% of the total cell-associated latex was released in 30 h. Internalisation of latex beads was demonstrated by electron microscopy. No uptake was detected in experiments conducted at 4 degrees C.

Cell Cycle↗
PubMed1975

Why are ovarian teratomas benign whilst teratomas of the testis are malignant?

A mechanism is suggested to account for the fact that most ovarian teratomas are benign (dermoid cysts) whereas testicular teratomas are almost always malignant. The mechanism advanced assumes that malignancy is cause by a recessive mutation, and then shows that the known facts of germ-cell development will produce the homozygous (malignant) state in the male but the heterozygous counterpart in the female. It is proposed that the benign nature of ovarian teratomas is a reflection of this heterozygous genotype.

Cell Differentiation↗
PubMed1975

The melanocytotoxic action of 4-hydroxyanisole.

Cultured normal mammalian melanocytes exposed to a variety of antioxidants in the presence of millimolar concentrations of 4-hydroxyanisole exhibit dose-dependent modifications of cytotoxicity. While some antioxidants reduced the extent of damage produced by 4-hydroxyanisole, others appeared to increase it. Similar effects were found in a model system using lysis of human erythrocytes as an index of cell damage. Estimations on rat liver microsomes in the presence of tyrosinase and 4-hydroxyanisole showed increased peroxidation only at low substrate concentrations.

Aldehydes↗