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Biomedical subjects

M K O'Farrell

Publications and source records attributed to M K O'Farrell.

10 recordsLinked to original sources
PubMed2000

The Th2 cytokine environment of the placenta.

It is now accepted that local changes to the balance of Th1/Th2-type cytokines occur during pregnancy within the maternal uterus and fetoplacental unit. These changes in cytokine profiles contribute to implantation of the embryo, development of the placenta, and survival of the fetus to term. Overall within the placenta there is a bias in the ratio of Th1:Th2 cytokines towards the Th2-type cytokines. However, there are specific fluctuations in this balance at implantation and during the initiation of parturition. The predominant cytokines at each stage of gestation function both to limit maternal immune rejection of the semi-allogeneic embryo/fetus, especially at the maternofetal interface; and to facilitate the on-going physiological processes within the maternal reproductive tract. These two, at times conflicting, roles are discussed in this review, with key evidence concerning cytokine expression and function from mouse and humans.

Allergens↗
PubMed1998

Higher plants possess two structurally different poly(ADP-ribose) polymerases.

One of the immediate reactions of the mammalian cell to many environmental stresses is a massive synthesis of poly(ADP-ribose), catalyzed by poly(ADP-ribose) polymerase (PARP). Most of the biological functions attributed to PARP are inferred from experimentation with mammalian cells. In plants, the biology of PARP may be more complicated and diverse than was previously thought. Two poly(ADP-ribose) polymerase homologues were found in plants, the classical Zn-finger-containing polymerase (ZAP) and the structurally non-classical PARP proteins (APP and NAP), which lack the characteristic N-terminal Zn-finger domain. By enzymatic and cytological experiments the recombinant APP protein was shown to be located in the nucleus and to possess DNA-dependent poly(ADP-ribose) polymerase activity in yeast. The nuclear localization was further confirmed by the analysis of transgenic tobacco plants that expressed a translational gene fusion between APP and the bacterial beta-glucuronidase. The app promoter was transcriptionally up-regulated in cells pre-determined to die because of deficiency in a DNA ligase I.

Amino Acid Sequence↗
PubMed1991

Down regulation of lamins A and C by murine interferon beta.

Treatment of spontaneously differentiated PSMB embryonal carcinoma cells with murine interferon beta results in a transient decrease in the expression of the nuclear lamins A and C. Reduced levels of mRNAs were observed 4 h after the addition of interferon beta, with reductions in the polypeptides and assembled proteins within the nuclear lamina seen after 8 h of treatment. Expression of the 72-kDa (lamin A) and the 62-kDa (lamin C) polypeptides remained down regulated for 8 h, returning to control levels after 16 h of interferon treatment. The specificity of this response is indicated by the inhibitory action of a neutralizing antibody to interferon.

Animals↗
PubMed1989

Interferon beta increases expression of vimentin at the messenger RNA and protein levels in differentiated embryonal carcinoma (PSMB) cells.

Murine interferon beta increases expression of the 58-kDa intermediate filament protein vimentin by differentiated PSMB cells. Enhanced amounts of vimentin mRNA and protein have been detected using Northern hybridization and Western blotting techniques. Immunocytochemical analysis demonstrates the increased assembly of the protein into the intermediate filament network and its relocalization around the cell nucleus. Induction follows a defined time course, with peak protein levels 16 h post interferon addition, followed by a gradual decline over the next 36 h.

Animals↗
PubMed1986

Metabolic turnover of proliferation-related nuclear proteins in serum-stimulated Swiss mouse 3T3 cells.

Stimulation of quiescent Swiss mouse 3T3 cells either by serum or by pure growth factors induces DNA synthesis after a lag period of about 15 h. Following restimulation by serum or by growth factors there is an overall increase of 2-4-fold in the rate of biosynthesis of nuclear proteins. Two nuclear polypeptides show specific temporal correlations with the transition from quiescence to proliferation. The synthesis of p30 (30 kDa, pI 5.2) is at a maximum within 5 h of restimulation, while the synthesis of p36 (36 kDa, pI 4.25) is first seen at 10-12 h after restimulation. The synthesis of p36 correlates well with the initiation of DNA biosynthesis. The metabolic turnover of both of these proteins has been estimated by pulse-chase and by cycloheximide inhibition experiments. They both have a half-life of 10-15 h and appear to be cell-cycle related.

Animals↗
PubMed1986

Biosynthesis of nuclear proteins after stimulation of quiescent Swiss mouse 3T3 cells.

Stimulation of quiescent Swiss mouse 3T3 fibroblasts either by serum or by the low molecular weight hormones, prostaglandin F2 alpha and insulin, induces DNA synthesis after a lag period of about 15 h. Following restimulation by serum or these pure hormones there is an overall increase of two- to fourfold in the rate of biosynthesis of nuclear proteins. In addition, there is a relative decrease in some proteins (Mr = 200 X 10(3), pI 6.0-6.5), while others increase (e.g. actin). Two polypeptides show specific correlations with the exit from G0. The synthesis of p30 (Mr = 30 X 10(3), pI 5.2) is at a maximum within 5 h of restimulation, while the synthesis of p36 (Mr = 36 X 10(3), pI = 4.25) is first seen at 10-20 h after restimulation. Synthesis of p36 correlates well with the initiation of DNA synthesis. The synthesis of both proteins is stimulated by serum and by the hormones. Thus there are common biosynthetic responses to different stimuli indicating convergent pathways leading to DNA biosynthesis. Addition of hydrocortisone with the growth-stimulatory hormones inhibits both entry into the S phase and biosynthesis of p36. In contrast, hydrocortisone does not alter the biosynthesis of p30. This 'early' protein, p30, is different from the products of both c-fos and c-myc. Therefore, we have identified two specific components that might participate in the regulation of cell proliferation.

Animals↗
PubMed1977

Temporal sequence of hormonal interactions during the prereplicative phase of quiescent cultured 3T3 fibroblasts.

After addition of prostaglandin F2alpha (PGF2alpha) and insulin to quiescent cultured 3T3 fibroblasts a constant lag phase of 15 hr occurs before an increased rate of cellular exit from G1 is observed. The latter process follows first order kinetics, which can be quantified by a rate constant k. The temporal relationship of the interactions of PGF2 alpha, insulin, and hydrocortisone to produce alterations in the rate of exit from G1 was investigated. PGF2alpha establishes a constant lag phase and produces alterations in the rate constant k. These two effects can be partially separated by adding two concentrations of PGF2alpha at different times. Insulin fails to establish the lag phase but can stimulate the effect of PGF2alpha when added at any time after PGF2alpha. Hydrocortisone reduces the value of k when added between 0 and 3 hr after PGF2alpha. These results show that the lag phase can beseparated into temporal regions during which hormones can interact to produce changes in the rate of cellular exit from G1.

Cell Line↗
PubMed1975

Poly(adenosine diphosphate ribose) polymerase in Physarum polycephalum.

1. The isolated nuclei of the slime mould Physarum polycephalum contain an enzyme that will incorporated [adenine-3H] NAD+ into an acid-insoluble product, which is shown to be poly(ADP-ribose). 2. This incorporation has an optimum pH of 8.2 and a temperature optimum below 10degreesC. 3. Optimum stimulation is given by 15 mM-Mg2+. 4. 2-Mercaptoethanol or dithiothreitol also stimulates the incorporation, the latter at an optimum concentration of about 1 mM. 5. Under optimum conditions the Km value for the reaction is 0.28 mM at 15degreesC. Nicotinamide inhibits the incorporation with a Ki of 5.7 muM. 6. Exogenous DNA stimulates the incorporation by about 100%. 7. Preincubation of the nuclei with deoxyribonuclease, but not with ribonuclease, almost completely inactivates the incorporation of NAD+. 8. The enzyme is unstable at both 0degrees and 15degreesC in the absence of dithiothreitol. The presence of dithiothreitol at a concentration of 1 mM stabilizes the enzyme at both these temperatures. 9. The activity of this enzyme per nucleus was shown in three separate experiments to fall by about one-half in early S phase and then to rise to its pre-mitotic value after about 3 h, that is in late S phase. 10. The possible physiological function of this enzyme system is discussed.

Cell Nucleus↗