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Biomedical subjects

J J Cooper

Publications and source records attributed to J J Cooper.

10 recordsLinked to original sources
PubMed2001

Blasts from elderly acute myeloid leukemia patients are characterized by low levels of culture- and drug-induced apoptosis.

Increasing evidence suggests that the biology of acute myeloid leukemia (AML) may differ between older and younger patients, with a higher incidence of antecedent myelodysplasia, unfavorable cytogenetic abnormalities, and multidrug resistance seen in the elderly. Abrogation of apoptosis in response to cytotoxic medications is associated with drug resistance in AML, as is expression of bcl-2, an important anti-apoptotic protein. We hypothesized that blasts from elderly (> or = 55 years) and young adult AML patients might have different levels of apoptotic and cell cycle responses to chemotherapeutic agents, as well as different levels of proliferation and of bcl-2 protein expression. Therefore, we cultured bone marrow leukemia samples from previously untreated elderly (n=33) and young (n=21) AML patients for 48 h and then measured apoptosis, bcl-2 protein levels, cell cycle distributions, and expression of a proliferation marker, proliferating cellular nuclear antigen (PCNA) in multi-parametric flow cytometry assays. In some experiments, leukemia samples were exposed to cytarabine (Ara-C) or daunomycin (DNR) for the last 16-18 h of the culture period. In comparison to samples from young patients, cultured samples from elderly AML patients had a higher fraction of viable cells, as measured by Trypan blue exclusion, higher PCNA expression, and significantly less culture-induced and drug-induced apoptosis. The mean apoptosis after culture was 13% for elderly AML samples, versus 20% for young AML samples (P=0.009). Similarly, the mean apoptosis after Ara-C was lower in elderly than in young AML samples, 13 versus 28% (P=0.001), as was the mean apoptosis after DNR, 15 versus 26% (P=0.012). Diminished apoptotic responses in elderly AML cells were not consistently associated with high bcl-2 levels at thaw or bcl-2 levels increased by culture. These data suggest that new therapies should be developed to overcome abrogated apoptosis, particularly in elderly AML patients.

Acute Disease↗
PubMed1999

The PIM-1 serine kinase prolongs survival and inhibits apoptosis-related mitochondrial dysfunction in part through a bcl-2-dependent pathway.

We have examined potential mechanisms by which the Pim-1 kinase acts as a hematopoietic cell survival factor. Enforced expression of the wild type 33 kd (FD/hpim33) and 44 kd (FD/mpim44) Pim-1 proteins in murine factor-dependent FDCP1 cells prolonged survival after withdrawal of IL-3, while expression of a dominant negative Pim-1 protein (FD/pimNT81) shortened survival. Following removal of IL-3 FDCP1 cells exhibited loss of mitochondrial transmembrane potential and production of reactive oxygen species, as determined by flow cytometry analysis. The wild type Pim-1 proteins decreased these changes while the dominant negative protein enhanced mitochondrial dysfunction. The antiapoptotic activity of the kinases could not be attributed to modulation of glutathione, catalase, or superoxide dismutase activities. Both the FD/hpim33 and FD/mpim44 cells maintained expression of bcl-2 mRNA following cytokine removal, while a substantial decrease was seen in FD/neo cells. To modulate Bcl-2 protein levels, a bcl-2 antisense RNA construct was coexpressed with the wild type pim-1 cDNAs. FD/hpim33 cells with low cellular Bcl-2 protein levels had shortened cytokine-independent survival compared with FD/hpim33 clones with high Bcl-2 expression. However survival of FD/mpim44 cells after IL-3 withdrawal was substantially independent of cellular Bcl-2 protein levels. The 33 kd protein delayed, and the 44 kd protein completely prevented enhanced cell death associated with enforced expression of human Bax protein however. Our results suggest that the 33 kd Pim-1 kinase may enhance cell survival through cooperation with and regulation of bcl-2. In addition the 44 kd kinase may regulate the expression or activity of other pro- and anti-apoptotic members of the bcl-2 family.

Animals↗
PubMed1998

The identification of abnormal behaviour and behavioural problems in stabled horses and their relationship to horse welfare: a comparative review.

Many behaviours in domestic animals, such as the 'stable vices' of horses, are treated because they are considered undesirable for economic or cultural reasons, and not because the activity affects the horse's quality of life. The impact of a behaviour on the human reporter is not a function of its impact on the animal performer, and an understanding of the causes and effects of the particular activity is necessary to assess the costs and benefits of treatment. Where the behaviour is a sign of poor welfare, such as an inadequate environment, treatment can best be achieved by removing these underlying causal factors. Pharmacological or physical prevention of a behaviour can be justified only if the behaviour causes harm to the performer or to others. In these cases, prevention of the behaviour without addressing its causes is no cure and may result in its perseverance in a modified form or the disruption of the animal's ability to adapt to its environment. Where the behavioural 'problem' causes no harm and is not related to poor housing, then the education of the reporter, rather than treatment of the performer, may be the best solution.

Animal Welfare↗
PubMed1998

Comparative learning theory and its application in the training of horses.

Training can best be explained as a process that occurs through stimulus-response-reinforcement chains, whereby animals are conditioned to associate cues in their environment, with specific behavioural responses and their rewarding consequences. Research into learning in horses has concentrated on their powers of discrimination and on primary positive reinforcement schedules, where the correct response is paired with a desirable consequence such as food. In contrast, a number of other learning processes that are used in training have been widely studied in other species, but have received little scientific investigation in the horse. These include: negative reinforcement, where performance of the correct response is followed by removal of, or decrease in, intensity of a unpleasant stimulus; punishment, where an incorrect response is paired with an undesirable consequence, but without consistent prior warning; secondary conditioning, where a natural primary reinforcer such as food is closely associated with an arbitrary secondary reinforcer such as vocal praise; and variable or partial conditioning, where once the correct response has been learnt, reinforcement is presented according to an intermittent schedule to increase resistance to extinction outside of training.

Animals↗
PubMed1996

Individual variation in prelaying behaviour and the incidence of floor eggs.

1. Floor eggs are a problem in non-cage systems for laying hens, as they require secondary egg collecting. Failure to lay in a well-defined nest site may also be a welfare problem for the hens, but only if their nesting motivation has been thwarted. We investigated the relationships between a hen's prelaying behaviour and its tendency to lay on the floor by recording the behaviour of 20 hens housed individually in wire cages with single littered nest boxes. 3. Most floor eggs (80%) were laid by the same 6 hens. These 6 "floor-layers" performed more nest seeking behaviour, less nest-building behaviour and less sitting prior to oviposition than the 14 hens that consistently laid in nest boxes. 4. The incidence of floor eggs declined with age. Both nest and floor laying hens performed less nest seeking behaviour with age. Floor layers, however, increased their performance of nesting behaviour, whilst nest layers performed less nesting behaviour with age. 5. Floor laying hens behaved as if they found the nest box less attractive than nest-laying hens; perhaps because they had lower nesting motivation, or perhaps because their nesting motivation was as high, but they less readily perceived the nest box as an appropriate nest site.

Animals↗
PubMed1993

Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material.

This study evaluates the mechanical properties of a composite material comprising polyhydroxybutyrate with hydroxyapatite added in proportions varying from 0 to 50%. Among the three methods of production, injection moulding was found to result in the most satisfactory mechanical properties. The tensile and compressive strength and the modulus of elasticity of composite produced in this way fell within the range for fresh human bone from different anatomical sites. With the additional advantages of biocompatibility, biodegradability and the potential for piezoelectric stimulation of new local bone formation, it was concluded that the injection-moulded composite material has considerable potential for use in orthopaedic surgery, both as a material to construct certain orthopaedic implants and as an alternative to corticocancellous bone graft.

Biocompatible Materials↗
PubMed1979

Abortion.

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Abortion, Legal↗