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T B Kirkwood

Publications and source records attributed to T B Kirkwood.

16 recordsLinked to original sources
PubMed1979

In vivo recovery of factor VIII: a comparison of one-stage and two-stage assay methods.

The recovery and half-life of VIII:C in the plasma of severely haemophilic patients was measured by one-stage and two-stage assays after injection of two Factor VIII concentrates (Hemofil, Hyland and Fraction I-O, Kabi). Plasma volumes were measured with an Evans' Blue technique, and both concentrates and post-infusion samples were measured against the same plasma standard. There was a highly significant difference in recoveries estimated by the two assay methods. The one-stage assays gave the most consistent results, in that the average recovery was 100%, whereas the two-stage assays gave only about 80% of the value expected from in vitro assays. There was no differences in recoveries between the two concentrates. The two-stage assays gave a slightly shorter half-life than the one-stage assays, and the half-life of Hemofil was also shorter than that of Fraction I-O.

Biological Assay↗
PubMed1979

The evolution of ageing and longevity.

Ageing is not adaptive since it reduces reproductive potential, and the argument that it evolved to provide offspring with living space is hard to sustain for most species. An alternative theory is based on the recognition that the force of natural selection declines with age, since in most environments individuals die from predation, disease or starvation. Ageing could therefore be the combined result of late-expressed deleterious genes which are beyond the reach of effective negative selection. However, this argument is circular, since the concept of 'late expression' itself implies the prior existence of adult age-related physiological processes. Organisms that do not age are essentially in a steady state in which chronologically young and old individuals are physiologically the same. In this situation the synthesis of macromolecules must be sufficiently accurate to prevent error feedback and the development of lethal 'error catastrophes'. This involves the expenditure of energy, which is required for both kinetic proof-reading and other accuracy promoting devices. It may be selectively advantageous for higher organisms to adopt an energy saving strategy of reduced accuracy in somatic cells to accelerate development and reproduction, but the consequence will be eventual deterioration and death. This 'disposable soma' theory of the evolution of ageing also proposes that a high level of accuracy is maintained in immortal germ line cells, or alternatively, that any defective germ cells are eliminated. The evolution of an increase in longevity in mammals may be due to a concomitant reduction in the rates of growth and reproduction and an increase in the accuracy of synthesis of macromolecules. The theory can be tested by measuring accuracy in germ line and somatic cells and also by comparing somatic cells from mammals with different longevities.

Adaptation, Biological↗
PubMed1979

Human cells and the finite lifespan theory.

Cultures of human diploid fibroblasts are characterized by: i) finite lifespan, ii) marked heterogeneity in the growth potential of individual cells within the culture, iii) considerable variation in lifespans of parallel cultures of the same cell strain. To explain these properties, we have proposed a commitment theory of cellular aging. Cells are assumed initially to be uncommitted (potentially immortal) but, at each cell division, each daughter cell is assumed to have some fixed probability of becoming irreversibly committed to senesce and die after a specific number of cell generations. During the period between commitment and senescence, cells are assumed to multiply normally, so the uncommitted cells are diluted by committed ones and may be lost in subculturing. The theory explains features i) - iii) above and, in particular, suggests why diploid cultures have finite lifespans while transformed or permanent lines grow indefinitely. It also validly predicts the behaviour of mixed cultures of distinguishable but otherwise similar cell types, and that culture lifespan may be significantly decreased by drastic reduction of population size. The important converse prediction that culture lifespan may be extended indefinitely by growing sufficiently large cultures or by selectively isolating uncommitted cells remains to be tested.

Cell Division↗
PubMed1978

International collaborative study of assay of anti-D (anti-Rh) immunoglobulin.

An international collaborative study of anti-D assays has been carried out by 21 laboratories in 11 countries. Samples of anti-D immunoglobulin assayed in this study included two dilutions of a preparation used in clinical trials to determine a dose-protection relation, a national standard, commercial clinical preparations and the proposed international reference preparation in coded ampoules. Manual, automated haemagglutination and isotope labelling methods all gave similar relative potencies. Several of these estimates were significantly (P=0.95) heterogeneous and some modifications to improve assay design and procedure are suggested. The coded preparation was shown to be stable and suitable for comparative assays. It was estimated to contain 60 microgram of of anti-D IgG immunoglobulin per ampoule, and 150 i.u./ampoule when assayed against the International Standard for Incomplete Anti-D Blood Typing Serum. Thus for this preparation 1 microgram of IgG anti-D immunoglobulin identical to 2.5 i.u. anti-D antibody. At its 28th meeting the Expert Committee on Biological Standardization of WHO established the preparation 68/419 as the International Reference Preparation of Anti-D Immunoglobulin and assigned to it a potency of 150 i.u. per ampoule. The Preparation has been widely used (with a nominal content of 60 microgram of IgG anti-D immunoglobulin) for control of clinical preparations.

Hemagglutination Tests↗
PubMed1978

Discrepancy between one-stage and two-stage assay of factor VIII:C.

Two methods (one-stage and two-stage) are commonly used for the assay of factor VIII clotting activity (VIII:C). We present collected data from seven separate studies of VIII:C assay which show that these methods do not give the same result when comparing concentrates and plasma. On average, two-stage assays detect 20% more VIII:C activity in concentrates as compared to plasmas than do one-stage assays.

Factor VIII↗
PubMed1978

Unreliability of chromogenic substrates for assay of the clotting activity of thrombin.

The rapid loss in clotting activity of commercially available thrombins during storage is not reflected by their activity as measured by synthetic chromogenic substrates. It is suggested that conformational changes occurring during storage can affect the binding sites of thrombin for fibrinogen, whereas small synthetic substrates are incapable of monitoring these changes.

Animals↗
PubMed1978

The stability of standards for radioimmunoassay of human TSH: research standard A and the international reference preparation initially 68/38.

The stability of the International Reference Preparation of human TSH for immunoassay (previously distributed in ampoules coded 68/38) and of Research Standard A for HTSH has been examined by radioimmunoassay of accelerated degradation samples (stored as the dry ampouled preparations). Potency estimates on degradation samples suggest a high order of stability of immunopotency recognisable by two antisera (MRC 72/356 and Hunter 3A). For the International Reference Preparation the loss of immunopotency during storage at -20 degrees C is predicted to have been 0.56% per year.

Drug Stability↗
PubMed1977

Evolution of ageing.

An evolutionary view of ageing suggests that mortality may be due to an energy-saving strategy of reduced error regulation in somatic cells. This supports Orgel's 'error catastrophe' hypothesis and offers a new basis for the study of normal and abnormal ageing syndromes and of apparently immortal transformed cell lines.

Aging↗
PubMed1977

Activation of plasminogen as a feature in its assay.

Seven laboratories collaborating in a study of two intermediate purity plasminogen preparations (64/23, 63/6) observed that the amount of activator (urokinase or streptokinase) and the time of activation of plasminogen influenced the amount of plasmin generated. Using casein and a synthetic polypeptide (S-2251) as substrates, the authors subsequently showed that complete activation of plasminogen was difficult to achieve without acitivity losses due to plasmin autodigestion. Comparison of the polypeptide subunits (on SDS electrophoresis) of the various plasminogen activation mixtures with their plasmin activity allowed the conclusion that at maximum generation of plasmin from plasminogen, some plasminogen remains in the form of an inactive plasminogen intermediate (PLG-i).

Caseins↗
PubMed1977

Predicting the stability of biological standards and products.

A high level of stability is essential for any biological standard and is desirable in most other biological products. It is in general impossible to observe directly the rate of degradation of a biological standard since no independent scale of measurement is available. An indirect method is therefore required. The most common approach is the accelerated degradation test in which samples are stored for a time at elevated temperatures and then compared with samples stored continuously at low temperature. The relative degradation rates are used to fit the Arrhenius equation (relating degradation rate to temperature) and hence to predict stability under normal storage conditions. Previous statistical work on this problem is reviewed and a maximum likelihood ML approach is suggested which overcomes some of the limitations of the existing methodology. The accelerated degradation test also finds wide application in the shelf-life prediction of biological products where the same statistical methods are appropriate.

Biological Products↗
PubMed1975

A standard for human plasmin.

An international collaborative study involving ten laboratories was undertaken to assess the suitability of a preparation of human plasmin in 50% glycerol to serve as a single standard for the bioassay of plasmin activity. The study included examination of the stability of the proposed standard and comparisons between assay methods. The results suggest that the human plasmin preparation coded 72/379 is suitable to serve as a standard. It is sufficiently stable to define the unit of plasmin activity for several years at or below 4 degrees C and for short periods at about 20 degrees C. The preparation has been assigned a potency of 8 units per ml. The International Committee on Thrombosis and Haemostasis (Basle, 1974) has recommended the use of this material as a standard.

Drug Stability↗