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O McGuinness

Publications and source records attributed to O McGuinness.

7 recordsLinked to original sources
PubMed1995

The exit of mouse oocytes from meiotic M-phase requires an intact spindle during intracellular calcium release.

To study the role of the metaphase spindle during the period of oocyte activation, mouse oocytes were fertilised or activated parthenogenetically in the presence or absence of the microtubule inhibitor nocodazole. In both cases, nocodazole caused the disappearance of the spindle and prevented the passage of the oocytes into interphase. However, the calcium spiking responses of the oocytes were not affected by nocodazole, being repetitive after fertilisation and a single spike after activation. If, after their activation or fertilisation in nocodazole, oocytes were later removed from the drug, only those that had been fertilised progressed into interphase. This progress was associated with continuing calcium spiking. Moreover, both the spiking and the progress to interphase could be blocked or reduced in incidence by removal of external calcium or addition of 5,5'-dimethyl BAPTA-AM. Oocytes that had been activated by ethanol in the presence of nocodazole and then removed from it, to allow re-formation of the spindle, only progressed into interphase if given a second exposure to ethanol, thereby eliciting a second calcium transient. These results show that exit from meiotic M-phase requires the simultaneous presence of a fully intact spindle during the release of calcium and that those factors leading to the degradation of cyclin B are only activated transiently. Since cyclin is being degraded continuously in the metaphase-II-arrested mouse oocyte and since this degradation is microtubule-dependent, these data suggest that the superimposition of a high concentration of intracellular calcium is required to tilt the equilibrium further in favour of cyclin degradation if exit from M-phase is to occur.

Animals↗
PubMed1993

On the involvement of a cyclosporin A sensitive mitochondrial pore in myocardial reperfusion injury.

Mammalian cardiomyocytes may withstand prolonged periods of ischaemia, only to die on reperfusion. We review data that implicate mitochondrial dysfunction as a basis for reperfusion induced cell injury, and present some new evidence that suggests that such a mechanism operates in intact cardiomyocytes. The mitochondrial dysfunction is the consequence of the opening of high conductance pores in the inner mitochondrial membrane, which uncouple mitochondrial oxidative phosphorylation, promoting ATP hydrolysis. The conditions required to open the pores correlate closely to conditions that prevail upon reperfusion of the ischaemic heart: a high [Ca2+]i and Pi, low [ATP], and oxidative stress. Pore opening is suppressed by physiological concentrations of ATP. Pore opening may be prevented by cyclosporin A. Studies in isolated myocytes show that mitochondria become uncoupled after reoxygenation, and that this is associated with the hypercontracture that signals cell death. Cyclosporin A reduces the proportion of hypercontracted myocytes in populations of cells rendered anoxic.

Adenosine Triphosphate↗
PubMed1992

The involvement of cyclosporin A binding proteins in regulating and uncoupling mitochondrial energy transduction.

The uncoupling of mitochondrial energy transduction by excess Ca2+ may be a factor in the pathogenesis of tissue injury brought about by energy deprivation, for example, in ischaemia. In isolated mitochondria the lesion appears as a large, 20 A, pore in the inner membrane. The pore is blocked potently by the immunosuppressant cyclosporin A. Cyclosporin A also markedly retards collapse of the mitochondrial inner membrane potential in energy-deprived (respiration-inhibited) cardiomyocytes as judged by changes in rhodamine 123 fluorescence, and prolongs cell viability. A potential mitochondrial target for cyclosporin A is the matrix protein cyclophilin. Purified cyclophilin activates the respiratory chain of submitochondrial particles. This might reflect not only a physiological function of this protein, but also a component involved in the generation of the 20 A pore under pathological conditions.

Animals↗
PubMed1991

Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.

OBJECTIVE: To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN: A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS: 347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING: Departments of immunology and genitourinary medicine, St Mary's Hospital, London. MAIN OUTCOME MEASURES: Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposi's sarcoma. RESULTS: The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposi's sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi's sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS: The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The presence of two classes of high-affinity cyclosporin A binding sites in mitochondria. Evidence that the minor component is involved in the opening of an inner-membrane Ca(2+)-dependent pore.

The inner membrane of rat liver mitochondria contains a reversible Ca(2+)-dependent pore, opening of which is largely blocked by cyclosporin A. Analyses of [3H]cyclosporin binding to rat liver mitochondria demonstrate two classes of high-affinity binding site with capacities of less than 5 pmol and approximately 60 pmol cyclosporin.mg mitochondrial protein-1 in addition to partitioning into membrane phospholipids (0.03 pmol.mg mitochondrial protein.nM-1). Direct measurement [14C]sucrose entry into the matrix space indicates that cyclosporin A inhibits pore opening by interacting with the low-capacity sites. The same low-capacity sites (Kd cyclosporin, 8 nM) are possibly attributable to peptidylprolyl cis-trans-isomerase, although investigation of pore state interconversion from the rapid kinetics of [14C]sucrose entrapment in the matrix space does not indicate that cyclosporin-sensitive prolyl isomerization occurs at the actual step of pore opening/closure. It is suggested that the low-capacity cyclosporin-binding component may stabilize the open pore state; this is supported by the observations that Ca2+ decreases cyclosporin binding to this component and that cyclosporin brings about closure of the pre-opened pore. The implications for the possible number of functional pores in mitochondria are discussed.

Amino Acid Isomerases↗
PubMed1981

Increased muscle oxygen consumption during electrical stimulation following endotoxin administration.

In this study, skeletal muscle oxygen demand was increased by electrical stimulation to determine if restricted oxygen supply to skeletal muscle in endotoxin-treated dogs was limiting oxygen consumption. Skeletal muscle blood flow was measured directly and arterio-venous differences of oxygen were determined in hindlimb muscles by obtaining blood samples simultaneously from the carotid artery and profunda femoris veins. Hindlimb muscle stimulation did not influence the systemic hemodynamic parameters monitored in either saline or endotoxin treated animals, although endotoxin treated animals demonstrated the well-characterized hemodynamic changes. During stimulation, skeletal muscle oxygen consumption was elevated due to increased oxygen extraction and blood flow in both treatment groups. No significant difference in oxygen consumption by nonstimulated muscle was observed between treatment groups. However, muscle oxygen extraction following endotoxin was greater than either pre-treatment or saline extraction values. This study demonstrates that following endotoxin administration, oxygen extraction by skeletal muscle is not maximal, and the muscle can further increase oxygen extraction with greater oxygen demand. Thus, skeletal muscle oxygen supply is not limiting the oxygen consumption following endotoxin treatment.

Animals↗