Slumbering time-bomb.
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Bone Density Conservation Agents↗
Biomedical subjects
F Dean
Publications and source records attributed to F Dean.
Visual outcomes and amblyogenic risk factors in craniosynostotic syndromes: a review of 141 cases.
AIMS: To determine the visual outcome and prevalence of amblyogenic risk factors in children with craniosynostotic syndromes. METHODS: The case notes of 141 children seen within the craniofacial unit were reviewed and information retrieved on date of birth, age at first and last examination, cycloplegic refraction at last visit, best corrected visual acuity at last visit, horizontal ocular deviation in primary position at first visit, and alphabet pattern if any. The presence of astigmatism, its magnitude, and orientation of axis were determined. RESULTS: 40.3% of patients had 1 dioptre (D) of astigmatism or greater and, of these, 64% had oblique astigmatism in at least one eye. Anisometropia of 1D or more was found in 18% of patients (age matched normals 3.5%). Horizontal strabismus was found in 70% (38% exotropia, 32% esotropia). Visual outcome results showed 39.8% of patients (45 of 113) had visual acuity of 6/12 or worse in their better eye. CONCLUSION: In the largest study to date a poor visual outcome was shown in children with Crouzon's, Pfeiffer's, Apert's, and Saethre-Chotzen syndromes (39.8% with 6/12 or worse in the better eye) together with significant prevalence of amblyogenic risk factors.
Adolescent↗
Prenatal glucocorticoid modifies hypothalamo-pituitary-adrenal regulation in prepubertal guinea pigs.
We hypothesized that exposure to synthetic glucocorticoid during rapid brain growth (d50-52, birth = 68 days) in fetal guinea pigs modifies hypothalamo-pituitary-adrenal (HPA) function after birth, and that this involves changes in central corticosteroid receptor regulation. On the basis of our previous studies, we proposed that this effect is sex-specific. Pregnant guinea pigs were treated with dexamethasone (1 mg/kg) or vehicle on d50-51 of gestation, and juvenile offspring were euthanized at rest or following isolation stress on postnatal day 18. Dexamethasone increased the length of gestation (1.5 days) and altered body and organ (brain, heart, adrenal) growth. Resting plasma cortisol concentrations were significantly elevated in young male, but not female guinea pigs exposed to dexamethasone as fetuses. In female offspring born to dexamethasone-treated mothers, cortisol responses to isolation stress were attenuated. In males, elevated basal cortisol levels were not increased further by isolation. In the brain, hippocampal glucocorticoid receptor (GR) mRNA levels were significantly lower (10-25%) in females exposed to dexamethasone in utero. In contrast, GR mRNA levels were elevated (10-20%) in males from this prenatal treatment group. Mineralocorticoid receptor mRNA in the limbic system and GR mRNA levels in the pars distalis were unaffected. Pro-opiomelanocortin mRNA was significantly lower (30%) in the male pars intermedia following dexamethasone exposure. In conclusion, prenatal glucocorticoid exposure affects growth and HPA function as well as limbic and hypothalamic GR expression in juvenile offspring, and these effects are highly sex-specific.
Animals↗
Maternal nutrient restriction (48 h) modifies brain corticosteroid receptor expression and endocrine function in the fetal guinea pig.
Modification of the fetal environment has been shown to program hypothalamo-pituitary-adrenal (HPA) development. Altered expression of brain corticosteroid receptors is thought to be central to this process. In the fetal guinea pig, rapid development of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) occurs in concert with rapid brain growth. Since nutrient availability has been associated with programming of endocrine function, we hypothesized that 48 h of maternal nutrient deprivation during rapid brain growth modifies the fetal endocrine environment and alters expression of GR and MR in the fetal brain. Pregnant guinea pigs were deprived of food (water available ad libitum) or fed normally on gestational days 50-51, and euthanized on gd52 (term=70 days). Nutrient deprivation caused intrauterine growth restriction (IUGR), though brain growth was protected. Fetal and maternal plasma cortisol was elevated in the deprived animals (p<0. 001), though plasma adrenocorticotrophin (ACTH) was only elevated in maternal blood. In deprived fetuses, plasma thyroxin levels were significantly (p<0.001) lower than control. GR mRNA levels were significantly decreased in the hypothalamic paraventricular nucleus (PVN; p<0.05) and CA1/2 (p<0.01) region of the hippocampus in female fetuses, and in the hippocampal CA1/2 in male fetuses (p<0.01). In contrast, MR mRNA levels were not changed by nutrient deprivation. In conclusion, 48 h of nutrient deprivation, activates the maternal, but not the fetal HPA axis, and decreases GR mRNA but not MR mRNA levels in the developing hypothalamus and limbic system. These developmental perturbations may have an important impact on the trajectory of corticosteroid receptor development and therefore central glucocorticoid feedback regulation.
Adrenocorticotropic Hormone↗
Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain.
Development of the fetal hypothalamo-pituitary-adrenocortical (HPA) axis is critical for fetal maturation and responses to stress. Guinea pigs, unlike rats, give birth to mature young, and peak brain growth occurs around days 48-52 (75%) of gestation. There is extensive development of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems at the time of rapid brain growth in guinea pigs. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids in late gestation, to promote fetal organ maturation, we tested the hypothesis that fetal exposure to glucocorticoids modifies developing GR and MR systems in the brain. Pregnant guinea pigs were subcutaneously injected with dexamethasone (dex; 1 mg/kg) or vehicle on days 50 and 51 of gestation (term=70 days). On day 52, guinea pigs were killed and the fetuses rapidly removed. Maternal dex treatment resulted in increased plasma cortisol concentrations in female fetuses, but decreased cortisol in male fetuses. Plasma thyroxine levels were increased in both female and male fetuses following maternal dex-treatment. Exposure to dex resulted in significant increases in MR and GR mRNA in the CA1-2 region of the hippocampus, and MR mRNA in the dentate gyrus in female fetuses. There was no effect of dex on GR or MR mRNA in the male fetuses. In conclusion, the effect of synthetic glucocorticoid on the developing brain GR and MR systems is sex-specific and is confined to very specific regions of the hippocampus. Since the hippocampus plays a central role in mediating glucocorticoid negative feedback of HPA function, alterations in the fetal development of corticosteroid receptors may form the basis of permanently modified HPA activity following fetal exposure to endogenous or synthetic glucocorticoid.
Adrenocorticotropic Hormone↗
GDS funding and NHS dentistry.
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Dental Health Services↗
Clamp loading, unloading and intrinsic stability of the PCNA, beta and gp45 sliding clamps of human, E. coli and T4 replicases.
BACKGROUND: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein ("sliding clamp') encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the beta subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. RESULTS: The PCNA ring is a stable trimer down to a concentration below 100 nM (Kd approximately 21 nM). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t1/2 approximately 24 min). beta is more stable in solution (Kd < 60 PM) and on DNA (t1/2 approximately 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (Kd approximately 250 nM) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and beta clamps on DNA necessitates an active process for their removal. The clamp loaders (RFC and gamma complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. CONCLUSIONS: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and beta clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and beta double as clamp unloaders presumably for the purpose of clamp recycling.
Bacteriophage T4↗
In vitro replication of duplex circular DNA containing the simian virus 40 DNA origin site.
Extracts (0.2 M NaCl) of HeLa cells support replication of DNA containing simian virus 40 (SV40) origin in the presence of SV40 large tumor (T) antigen. The reaction leads to the accumulation of high molecular weight products that represent DNA containing one parental strand and one progeny strand as well as duplex molecules that contain both strands derived from the input deoxynucleoside triphosphates. The replication reaction is inhibited by aphidicolin and by camptothecin, two inhibitors known to inhibit eukaryotic DNA replication in vivo.
Antigens, Viral, Tumor↗
Factor VIII procoagulant antigen recovery is a dose-related response to Factor VIII concentrate infusions.
The recovery and initial half-disappearance rate of factor VIII procoagulant activity (VIIIC) and procoagulant antigen (VIIICAg) were studied in 9 haemophilia A patients following infusion of factor VIII concentrates to varying plasma VIIIC levels. While VIIIC recovery was independent of dose, the VIIICAg recovery varied in a dose-dependent fashion. The excess of VIIICAg relative to VIIIC found in the factor VIII concentrates (VIIICAg/VIIIC ratios of 1.9-3.1) was not observed in plasma samples taken after low level infusions (plasma VIIIC less than 1 U/ml) but a significant excess of VIIICAg was observed in higher level infusions. The VIIICAg recovery of post-infusion plasma was not increased by treatment with phospholipase C.
Antigens↗
Escherichia coli type-1 topoisomerases: identification, mechanism, and role in recombination.
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Base Sequence↗
A comparison of "carrier screening" of hemophilia by the ratio of factor VIII coagulant activity or antigen to factor VIII related antigen.
The ratio of factor VIII coagulant activity (VIIIC) or antigen (VIIICAg) to that of factor VIII related antigen (VIIIRAg) was measured in 15 normals, 21 obligatory and 23 possible carriers of hemophilia. Factor VIII coagulant was measured on fresh plasma samples whereas antigenic properties were measured on frozen and thawed samples. In obligatory carriers only, the mean level of VIIICAg was significantly lower than VIIIC and there was a tendency for low VIIICAg levels to be associated with raised VIIIRAg levels. Using both ratios, 13 obligatory carriers were outside the normal tolerance ellipse. In possible carriers, neither ratio showed superior discriminating power. In reference laboratories that perform carrier studies on stored or transported specimens, measurement of VIIICAg/VIIIRAg is a suitable test for diagnosis of carriers.
Antigens↗
A diagnostic schema for identifying enterobacteriaceae and miscellaneous gram-negative bacilli.
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Bacteriological Techniques↗
Determination of the absolute handedness of knots and catenanes of DNA.
DNA winds about itself in a right-handed or left-handed fashion at several structural levels. The double helix is generally right-handed and is given a (+) sign by convention, whereas supercoiling of the helix axis is always (-) in the cell. The winding in higher -order forms such as knots and catenanes is unknown, and this has impeded elucidation of the mechanisms of their formation and resolution by replication, recombination and topoisomerase action. We introduce here a procedure for determining the handedness of DNA winding by inspection of electron micrographs of DNA molecules coated with Escherichia coli RecA protein. We demonstrate the validity of the method and show that DNA topoisomerase I of E. coli generates an equal mixture of (+) and (-) duplex DNA knots, and that one product of recombination by resolvase of transposon Tn3 (refs 8, 9) is a catenane of uniquely (+) sign.
Bacterial Proteins↗