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J Whelan

Publications and source records attributed to J Whelan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Unraveling the role of mitochondria during oxidative stress in plants.

The sedentary habit of plants means that they must stand and fight environmental stresses that their mobile animal cousins can avoid. A range of these abiotic stresses initiate the production in plant cells of reactive oxygen and nitrogen species that ultimately lead to oxidative damage affecting the yield and quality of plant products. A complex network of enzyme systems, producing and quenching these reactive species operate in different organelles. It is the integration of these compartmented defense systems that coordinates an effective response to the various stresses. Future attempts to improve plant growth or yield must consider the complexity of inter-organelle signaling and protein targeting if they are to be successful in producing plants with resistance to a broad range of stresses. Here we highlight the role of pre-oxidant, antioxidant, and post-oxidant defense systems in plant mitochondria and the potential role of proteins targeted to both mitochondria and chloroplasts, in an integrated defense against oxidative damage in plants.

Animals↗
PubMed2001

Gaining consent to freeze spermatozoa from adolescents with cancer: legal, ethical and practical aspects.

Sperm banking for early adolescent cancer patients requires delicate, sensitive handling and, in the UK, consideration is required of statutory elements. No information at present exists about how adolescents with cancer are normally treated or counselled for sperm banking. Here we highlight the type of issues in relation to fertility preservation faced by clinicians and those faced by adolescents at a sperm storage laboratory. We explore the very real difficulties of bringing together these medical fields of assisted reproduction, oncology and the various pieces of legislation and focus specifically on gaining consent. Attention is paid to counselling and communication to help the patient reach an effective and informed decision to store spermatozoa. The role of parents in contributing towards communication and support, together with the legal constraints in decision making, is acknowledged. How absolute and fully 'informed' consent should be will always remain a contentious issue amongst the various specialists and disciplines. In relation to sperm storage, as a minimum the patients should understand the process that they are undertaking so that it is undertaken freely and without pressure. The practical approach to gaining consent that we are using seems a logical and practical method to help early adolescent patients to store spermatozoa.

Adolescent↗
PubMed2001

Quantification of the common deletion in human testicular mitochondrial DNA by competitive PCR assay using a chimaeric competitor.

The "common" 4977 bp deletion in mitochondrial DNA (Delta4977) is commonly used as an indicator of tissue deterioration in ageing and bioenergetic diseases. Deletion levels are normally measured by a serial dilution polymerase chain reaction (PCR) approach, where test reactions are compared with dilutions of control amplifications of DNA from a similar sized stable region of the mitochondrial genome. The end-point of this assay is the dilution that can just detect any PCR product; however, this is an inherently unstable measure. We constructed a chimaeric DNA construct that binds to both control and deletion primers with similar annealing properties. This was used in a competitive PCR assay to quantify Delta4977 in human testicular tissues that had been well-characterized using the serial dilution approach. We found the competitive assay to be highly replicable as it compares the PCR product of the construct with that of test DNA samples during the linear growth phase of the PCR reaction. Moreover, the serial dilution assay was shown to significantly overestimate the amounts of deleted mitochondrial DNA present. The assay promises to throw new light on the role of mitochondrial DNA deletions in tissue dysfunction and ageing, as such deletions can now be determined with high accuracy and repeatability and is much cheaper to apply than real-time fluorescent quantitative PCR.

DNA, Mitochondrial↗
PubMed2001

The expression of alternative oxidase and uncoupling protein during fruit ripening in mango.

The expression of alternative oxidase (Aox) and uncoupling proteins (Ucp) was investigated during ripening in mango (Mangifera indica) and compared with the expression of peroxisomal thiolase, a previously described ripening marker in mango. The multigene family for the Aox in mango was expressed differentially during ripening. Abundance of Aox message and protein both peaked at the ripe stage. Expression of the single gene for the Ucp peaked at the turning stage and the protein abundance peaked at the ripe stage. Proteins of the cytochrome chain peaked at the mature stage of ripening. The pattern of protein accumulation suggested that increases in cytochrome chain components played an important role in facilitating the climacteric burst of respiration and that the Aox and Ucp may play a role in post-climacteric senescent processes. Because both message and protein for the Aox and Ucp increased in a similar pattern, it suggests that their expression is not controlled in a reciprocal manner but may be active simultaneously.

Blotting, Southern↗
PubMed2000

Repeated, recent and diverse transfers of a mitochondrial gene to the nucleus in flowering plants.

A central component of the endosymbiotic theory for the bacterial origin of the mitochondrion is that many of its genes were transferred to the nucleus. Most of this transfer occurred early in mitochondrial evolution; functional transfer of mitochondrial genes has ceased in animals. Although mitochondrial gene transfer continues to occur in plants, no comprehensive study of the frequency and timing of transfers during plant evolution has been conducted. Here we report frequent loss (26 times) and transfer to the nucleus of the mitochondrial gene rps10 among 277 diverse angiosperms. Characterization of nuclear rps10 genes from 16 out of 26 loss lineages implies that many independent, RNA-mediated rps10 transfers occurred during recent angiosperm evolution; each of the genes may represent a separate functional gene transfer. Thus, rps10 has been transferred to the nucleus at a surprisingly high rate during angiosperm evolution. The structures of several nuclear rps10 genes reveal diverse mechanisms by which transferred genes become activated, including parasitism of pre-existing nuclear genes for mitochondrial or cytoplasmic proteins, and activation without gain of a mitochondrial targeting sequence.

Amino Acid Sequence↗
PubMed2000

Malignant round cell tumours of bone: atypical clinical and imaging features.

OBJECTIVE: To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/primitive neuroectodermal tumour (PNET). DESIGN: Retrospective review of case notes and available imaging was carried out. PATIENTS: Six patients (4 male, 2 female; mean age 27 years, range 19-44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. RESULTS AND CONCLUSIONS: Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous "skip" metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear.

Adult↗
PubMed2000

Characteristics of patients presenting with central retinal artery occlusion with and without giant cell arteritis.

BACKGROUND: In patients with concurrent central retinal artery occlusion (CRAO) and giant cell arteritis (GCA), prompt recognition and early treatment are crucial to prevent further visual loss in the contralateral eye. The objective of this study was to describe a series of patients with CRAO resulting from GCA and to compare them with patients with isolated CRAO. METHODS: The patient database for a retina service in Philadelphia was searched to identify patients admitted between 1983 and 1993 with a diagnosis of biopsyproven GCA and CRAO. For every patient with CRAO caused by GCA, the next patient admitted for management of acute isolated CRAO was identified; these latter patients constituted the control group. The visual acuity and baseline characteristics of the two groups were compared. RESULTS: Eleven patients with acute CRAO and GCA were admitted during the study period. In both the case and control groups seven patients (64%) were women and nine patients (82%) were white. Six subjects (54%) in the case group and seven (64%) in the control group had a history of hypertension; the values for diabetes mellitus were two (18%) and zero respectively. Four patients (36%) with CRAO and GCA were cigarette smokers, compared with eight patients (73%) with CRAO alone. None of these differences were statistically significant. Patients with CRAO related to GCA were more likely than those with isolated CRAO to have counting fingers or better vision at presentation (odds ratio 2.22 [95% confidence interval 0.37 to 13.2]), but this trend was not statistically significant. INTERPRETATION: Patients who presented with CRAO related to GCA were more than twice as likely as those with CRAO alone to have counting fingers or better visual acuity at the time of presentation. However, owing to the small sample, the power of this study to detect a true difference between the two groups was limited.

Adult↗
PubMed2000

Torsion-induced injury in rat testes does not affect mitochondrial respiration or the accumulation of mitochondrial mutations.

Male rats were subjected to 1 h testicular torsion of the spermatic cord or 1 h torsion followed by detorsion and recovery up to 4 weeks. The extent of tissue damage was evaluated by a testicular biopsy score count and mitochondrial function. Torsion for 1 h followed by detorsion induced significant morphological damage, which became more severe with longer periods of recovery. This morphological damage could not be correlated with mitochondrial damage as assessed by measuring the 4834 bp mitochondrial DNA 'common deletion' using a quantitative competitive polymerase chain reaction (PCR) assay. Mitochondrial respiratory chain activity, as measured by mitochondrial oxygen consumption using an oxygen electrode, did not vary between the treated animals and the controls. We conclude that the common mitochondrial DNA deletion and oxygen consumption are not good indicators of testicular damage induced by torsion.

Animals↗
PubMed2000

Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min/+)mice.

Epidemiologic and animal studies indicate that sustained use of non-steroidal anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the incidence of colorectal neoplasia and subsequent mortality. We previously demonstrated that sulindac significantly reduces intestinal tumor load in Apc(Min/+)mice and the tumor regression was not necessarily correlated with prostaglandin biosynthesis. In the present study, we further investigate the relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model. We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent, reducing tumor load by 85% and significantly inhibiting basal and ex vivo prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm) has a similar impact on reducing prostaglandin levels, but in contrast to indomethacin, is uneffective in reducing the tumor load. The data indicate a discordance between the impact of different NSAIDs on tumorigenesis in Apc(Min/+)mice.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice.

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in Apc(Min/+) mice.

The multiple intestinal neoplasia (Apc(Min/+)) mouse possesses a germline mutation at codon 850 of the adenomatous polyposis coli (Apc) gene resulting in the formation of a nonfunctional truncated gene product. Following a somatic mutation of the remaining wild-type allele, mice spontaneously develop approximately 40-50 tumors throughout the intestinal tract. This mouse model has been used to study intestinal tumorigenesis because this mutation is analogous to the inherited APC mutation in humans with familial adenomatous polyposis (FAP). These individuals characteristically develop numerous adenomas throughout their intestinal tracts. Only a few studies have evaluated the effects of dietary fatty acids on tumorigenesis in this animal model with varying results, and none have linked these effects to alterations in arachidonic acid (AA) metabolism. This study was designed to evaluate the antitumorigenic effect of dietary (n-3) polyunsaturated fatty acids (PUFA) in the Apc(Min/+) mouse model and to determine whether these effects are related to inhibition of AA metabolism. Male Apc(Min/+)mice were fed diets supplemented with eicosapentaenoic acid (EPA), AA or a combination of AA + EPA. Mean tumor number in the EPA group was 68% lower (P<0.05) compared with the control group, whereas AA supplementation did not significantly alter tumor load. The reduction in tumor load coincided with significant reductions in intestinal AA content and levels of prostaglandins. However, supplementing AA to the EPA diet (AA + EPA) abolished the antitumorigenic effect of EPA, increased tissue AA content fourfold and prostaglandin production two- to fourfold. These results indicate that AA is involved in tumorigenesis and suggest that EPA's ability to reduce tumor load in Apc(Min/+) mice is related to reductions in tissue AA content or its metabolism.

Analysis of Variance↗
PubMed1999

Import of precursor proteins into mitochondria from soybean tissues during development.

Characterisation of the amount of protein import of the alternative oxidase (AOX) and the F(A)d precursor proteins (previously shown to use different import pathways) into mitochondria from developing soybean tissues indicated that they displayed different patterns. Import of the AOX declined in both cotyledon and root mitochondria with increasing age, whereas the import of the F(A)d into cotyledon mitochondria remained high throughout the same period. Using primary leaf mitochondria, it was evident that import of AOX remained high while it declined in cotyledon and root mitochondria. The amount of import of the AOX into mitochondria from different tissues closely matched the amount of the Tom 20 receptor.

Biological Transport, Active↗