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Biomedical subjects

T Hay

Publications and source records attributed to T Hay.

10 recordsLinked to original sources
PubMed2005

DNA damage hypersensitivity in cells lacking BRCA2: a review of in vitro and in vivo data.

Since the discovery of the tumour suppressor BRCA2 (encoded by breast-cancer susceptibility gene 2), cells lacking the fully functional protein have consistently been found to show increased sensitivity to a variety of DNA-damaging agents, particularly those that cross-link DNA. In this short review, we will bring together these findings and discuss them in the light of our recent in vivo data in the mouse small intestine, which suggests that deletion of cells lacking Brca2 is necessary to avoid the development of potentially tumorigenic clones in this tissue, a system that may be less effective in the mammary glands of humans with germline mutations in BRCA2.

Animals↗
PubMed2001

Phosphorylation of murine double minute clone 2 (MDM2) protein at serine-267 by protein kinase CK2 in vitro and in cultured cells.

Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. MDM2 mediates the ubiqutination of p53 in the capacity of an E3 ligase and targets p53 for rapid degradation by the proteasome. Stress signals which impinge on p53, leading to its activation, promote disruption of the p53-MDM2 complex, as in the case of ionizing radiation, or block MDM2 synthesis and thereby reduce cellular MDM2 levels, as in the case of UV radiation. It is therefore likely that MDM2, which is known to be modified by ubiquitination, SUMOylation and multi-site phosphorylation, may itself be a target for stress signalling (SUMO is small ubiquitin-related modifier-1). In the present study we show that, like p53, the MDM2 protein is a substrate for phosphorylation by the protein kinase CK2 (CK2) in vitro. CK2 phosphorylates a single major site, Ser(267), which lies within the central acidic domain of MDM2. Fractionation of cellular extracts revealed the presence of a single Ser(267) protein kinase which co-purified with CK2 on ion-exchange chromatography and, like CK2, was subject to inhibition by micromolar concentrations of the CK2-specific inhibitor 5,6-dichlororibofuranosylbenzimidazole. Radiolabelling of cells expressing tagged recombinant wild-type MDM2 or a S267A (Ser(267)-->Ala) mutant, followed by phosphopeptide analysis, confirmed that Ser(267) is a cellular target for phosphorylation. Ser(267) mutants are still able to direct the degradation of p53, but in a slightly reduced capacity. These data highlight a potential route by which one of several physiological modifications occurring within the central acidic domain of the MDM2 protein can occur.

Amino Acid Sequence↗
PubMed2001

Genetic and demographic parameters determining population persistence after a discrete change in the environment.

Field studies suggest that populations often go extinct following discrete changes in the environment. However, populations may avoid extinction by rapidly adapting to their altered environment. We used a stochastic finite-locus model to estimate the distance the optimal value of a quantitative trait could shift in a single step Delta theta(c) without causing more than 5% of the replicate populations to go extinct. We found that evolution increased the magnitude of Delta theta(c) by at least two phenotypic standard deviations and that such evolution could take place within 5--10 generations. Indeed (Delta theta(c))(2) increased approximately linearly with the logarithm of the initial population size and the rate of this increase was much greater when heritability was high or when stabilizing selection was weak. (Delta theta(c))(2) also increased approximately linearly with the logarithm of per capita fecundity. To our surprise there was no 'demographic rescue' effect from migration; a population augmented with migrants from a neighbouring population where environmental conditions were unchanged was always more likely to go extinct. The addition of mutation, more loci, density-dependence, or environmental stochasticity had only small effects on the outcome. We were able to compare our results for closed populations with density-independent population growth to those from an analytical model and found good agreement so long as the proportion of the offspring surviving selection in the initial generations was at least 1%.

Animals↗
PubMed1999

Pediatric diffuse lung disease: diagnosis and classification using high-resolution CT.

OBJECTIVE: Our purpose was to categorize high-resolution CT findings in children with diffuse lung disease and to evaluate the accuracy of diagnoses made using CT. MATERIALS AND METHODS: The chest radiographs and high-resolution CT scans of 20 children (1-16 years old; median, 9 years old) with biopsy-proven chronic diffuse lung diseases were reviewed separately by two independent chest radiologists. Thirteen types of diffuse lung disease were included in the study. Radiographic and CT features were noted, and three choices of diagnosis were recorded, with the confidence level. RESULTS: Diagnoses were made with a high degree of confidence (definite or probable) in 25 of 40 interpretations of CT scans, compared with only five of 40 interpretations of chest radiographs (p < .001). Fourteen (56%) of the 25 confident first-choice diagnoses on CT scans were correct, compared with two (40%) of the five interpretations on chest radiographs. Diseases were classified as belonging to one of five distinct groups on the basis of dominant CT features. Airway disease (n = 5) (bronchiolitis obliterans or bronchocentric granulomatosis) showed geographic hyperlucency on CT. Septal disease (n = 4) (lymphangiomatosis, hemangiomatosis, or microlithiasis) showed septal thickening. Infiltrative lung disease (n = 7) (desquamative interstitial pneumonitis, hypersensitivity pneumonitis, or lymphoid interstitial pneumonitis) showed ground-glass opacity. Air-space disease (n = 3) (aspiration, vasculitis, or bronchiolitis obliterans organizing pneumonia) showed lung consolidation. Langerhans' histiocytosis (n = 1) showed cysts and nodules. Surprisingly little overlap was seen among these groups. CONCLUSION: CT increases the level of diagnostic confidence for pediatric infiltrative lung disease, improves diagnostic accuracy, and provides a useful classification system.

Child↗
PubMed1997

Homelessness, severe mental illness, and the institutional circuit.

OBJECTIVE: Research on homelessness among persons with severe mental illness tends to focus on aspects of demand, such as risk factors or structural and economic forces. The authors address the complementary role of supply factors, arguing that "solutions" to residential instability-typically, a series of institutional placements alternating with shelter stays-effectively perpetuate homelessness among some persons with severe mental illness. METHODS: Thirty-six consecutive applicants for shelter in Westchester County, New York, in the first half of 1995 who were judged to be severely mentally ill by intake workers were interviewed using a modified life chart format. Detailed narrative histories were constructed and reviewed with the subjects. RESULTS: Twenty of the 36 subjects had spent a mean of 59 percent of the last five years in institutions and shelters. Analysis of the residential histories of the 36 subjects revealed that shelters functioned in four distinctive ways in their lives: as part of a more extended institutional circuit, as a temporary source of transitional housing, as a surrogate for exhausted support from kin, and as a haphazard resource in essentially nomadic lives. The first pattern dominated in this group. CONCLUSIONS: Shelters and other custodial institutions have acquired hybrid functions that effectively substitute for more stable and appropriate housing for some persons with severe mental illness.

Adolescent↗
PubMed1989

Absolute intracranial blood-flow velocities evaluated by duplex Doppler sonography in asymptomatic preterm and term neonates.

Thirty-eight asymptomatic preterm and term neonates were studied with pulsed Doppler sonography to assess absolute (true) intracranial blood-flow velocities. The middle and posterior cerebral arteries were evaluated by a transcranial approach, and the anterior cerebral artery was evaluated via the anterior fontanelle. Intracranial velocities were seen to increase with increasing gestational age and with increasing age of the neonate. The rate of increase in velocity was greater with higher gestational age. Middle cerebral artery velocities were greater than anterior cerebral velocities. Likewise, antegrade diastolic flow was always seen in these normal neonates. Intracranial velocities increased with gestational age and with increasing age of the child; the resistive index decreased progressively with age.

Blood Flow Velocity↗
PubMed1979

Seaward orientation of hatchling turtles: turning systems in the optic tectum.

This paper reports studies on the mechanisms underlying seaward orientation in hatchling turtles. The particular aim was to investigate whether activity in different regions of the retina and associated tectal areas, as assessed by some comparator mechanism, results in turning in different directions. Hatchling green turtles (Chelonia mydas) were tested for sea-finding ability in a natural situation on the beach following lesions of the optic tectum. Asymmetrical bilateral lesions resulted in a number of turtles making circles in the direction of the tectum with the posterior lesion and in other turtles deviated in this direction. Bilaterally lesioned turtles were also slower and less consistent in their sea-finding behaviour. No major disruptions of sea finding were detected in animals with unilateral tectal lesions. By suspending lights in the nasal visual field of unilaterally blindfolded green and leatherback turtles (Dermochelys coriacea) it was possible to produce circling in the direction of the covered eye; in contrast, with the light suspended in the temporal field, turning was always in the direction of the uncovered eye. The results are consistent with the view that sea finding depends on a complex phototropotactic system with stimulation in different parts of a single retina being associated with turning in opposite directions.

Animals↗
PubMed1969

Low cost milk production.

Explore the source record for details and available documents.

Animal Nutritional Physiological Phenomena↗
PubMedDate not supplied

Societal interventions to prevent child abuse and neglect.

A framework for understanding child maltreatment in terms of complex and interacting factors from the individual to the societal level can aid in conceptualizing and implementing prevention efforts. Research on interventions at the societal level can guide a broad range of activities, increasing their effectiveness and viability. Fundamental approaches include evaluation of specific interventions and systems-level research on implementation and development of best practice in prevention activities for different portions of society. Research can indicate the roles that each individual, agency, organization, community, and level of government can play. The U.N. Convention on the Rights of the Child provides a useful framework for societal level change to improve the welfare of children and families.

Child↗