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Biomedical subjects

P Perry

Publications and source records attributed to P Perry.

At least 19 recordsLinked to original sources
PubMed2007

Reprogramming of root epidermal cells in response to nutrient deficiency.

Post-embryonic development of the root system is highly plastic to environmental cues, compensating for the sessile lifestyle of plants. The fate of epidermal cells of Arabidopsis roots is particularly responsive to nutritional signals, leading to an increase in the root's surface area in the absence of the essential but immobile minerals iron, phosphate and manganese. The resulting phenotype is characteristic of the respective condition. Growth under nutrient starvation affects the expression of genes involved in cell specification, indicating that environmental signals are perceived at an early stage of cell development. Cell fate decisions are controlled at different levels, probably integrated at the level of chromatin organization.

Arabidopsis↗
PubMed2000

Functional interaction between E-cadherin and alphav-containing integrins in carcinoma cells.

We have demonstrated the possibility of cross-talk between E-cadherin and alphav integrins in breast carcinoma cells. Using the function-blocking anti-alphav monoclonal antibody 17E6, applied to monolayer cultures of breast cancer lines, it was found that treatment of cells possessing detergent-insoluble (implying attachment to the actin cytoskeleton) E-cadherin resulted in the adoption of a spheroid configuration of cell growth. This effect was dependent upon not just alphav occupancy but also receptor aggregation. Thus in vitro alphav-dependent adhesion suppresses E-cadherin-mediated morphological changes. To investigate whether manipulation of E-cadherin would, conversely, modulate integrin activity we introduced a dominant-negative E-cadherin construct into one of the lines, ZR75-1, giving rise to the cell line ZR-E2R1. Surface expression of endogenous E-cadherin was downregulated (by around 25%), whereas beta-catenin levels were increased two- to threefold in ZR-E2R1 cells. There was also a highly significant increase in migration of ZR-E2R1 cells (relative to control cells) toward vitronectin (P<0.001), but not toward collagen type I, fibronectin or laminin. Such increased migration could be abrogated totally by antibody blockade of alphavbeta5 and alphavbeta1 integrins. There was no detectable change in alphav integrin levels. These data suggest that the introduction of a dominant-negative E-cadherin mutant into ZR75-1, in addition to a loss of cohesion, generates a signal (or signals) which increases migration towards vitronectin through increased activity of alphav integrins.

Actins↗
PubMed1999

Differences in the localization and morphology of chromosomes in the human nucleus.

Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.

Cell Cycle↗
PubMed1999

Identification and characterization of a homozygous deletion found in ovarian ascites by representational difference analysis.

We have performed representational difference analysis (RDA) on DNA from tumor cells and normal fibroblasts isolated from the ascites of a patient with ovarian cancer. Five of six products of the RDA were homozygously deleted from the tumor DNA. One of these products has been characterized and identifies a homozygous deletion of approximately 6.9 Mb at chromosome 9p21 in the original ovarian tumor material. This deletion encompasses CDKN2A (p16), CDKN2B (p15), and IFN-alpha. PCR analysis of other tumor cell lines using the novel STS based on the RDA product has shown it to lie between IFN-alpha and p16, and to identify the distal extent of a homozygous deletion in another ovarian cancer cell line. These data provide further evidence for a tumor suppressor locus distinct from, but mapping close to, p16 on 9p21. Cytogenetic analysis using comparative genomic hybridization (CGH) performed on the same primary tumor confirmed a loss of material from chromosome 9p. However, the CGH technique had neither the resolution nor the sensitivity to define a subregion of homozygous loss.

Ascites↗
PubMed1998

Localization of the 26S proteasome during mitosis and meiosis in fission yeast.

The 26S proteasome is a large multisubunit complex involved in degrading both cytoplasmic and nuclear proteins. We have investigated the localization of this complex in the fission yeast, Schizosaccharomyces pombe. Immunofluorescence microscopy shows a striking localization pattern whereby the proteasome is found predominantly at the nuclear periphery, both in interphase and throughout mitosis. Electron microscopic analysis revealed a concentration of label near the inner side of the nuclear envelope. The localization of green fluorescent protein (GFP)-tagged 26S proteasomes was analyzed in live cells during mitosis and meiosis. Throughout mitosis the proteasome remained predominantly at the nuclear periphery. During meiosis the proteasome was found to undergo dramatic changes in its localization. Throughout the first meiotic division, the signal is more dispersed over the nucleus. During meiosis II, there was a dramatic re-localization, and the signal became restricted to the area between the separating DNA until the end of meiosis when the signal dispersed before returning to the nuclear periphery during spore formation. These findings strongly imply that the nuclear periphery is a major site of protein degradation in fission yeast both in interphase and throughout mitosis. Furthermore they raise interesting questions as to the spatial organization of protein degradation during meiosis.

Base Sequence↗
PubMed1998

An outcome evaluation of a hospital-based early intervention program.

AIM: To determine the effectiveness of the Health Care Intervention Service (HIS), an early intervention program for general hospital patients with alcohol dependence or at risk for alcohol dependence. DESIGN, SETTING AND PARTICIPANTS: HIS consists of screening, assessment and assignment to either full or risk-reduction intervention. Full intervention includes a referral to treatment. Outcomes were compared across three groups: those who received a full intervention, those who received a risk-reduction intervention, and a comparison group of similar patients from hospitals with no HIS program. Patients were screened for alcohol involvement and interviewed during their hospitalization (prior to the intervention in HIS hospitals) and again 6 months following the intervention. FINDINGS: Full intervention was effective in increasing the probability of abstinence, reducing the number of heavy drinking days, and encouraging patients to accept the referral to treatment. Risk-reduction intervention was effective in reducing alcohol consumption and consequences, but only for those patients who had some signs of dependence at the first interview. CONCLUSIONS: HIS has demonstrated its effectiveness in a "real world" bureaucratic and clinical environment.

Adult↗
PubMed1997

Scaffold attachments within the human genome.

It is generally agreed that, above the level of the 30 nm fibre, eukaryotic chromatin is constrained into loops, but there is disagreement about the nature of the substructure that serves to anchor loops and the DNA sequences that act as the attachment sites. This problem may stem from the very different methods that all purport to separate loop and attached DNAs. We have tested ideas about how the genome is arranged into loops by analysing the average loop size over different cytologically resolvable regions of human chromosomes using fluorescence in situ hybridisation with loop and attached DNA fractions. Variations in average loop size, along and between chromosomes, measurable at this level of resolution were small but significant and were dependent on the extraction method. This emphasises the fundamental differences between the nuclear substructure probed by different protocols. DNA attached to the nuclear 'scaffold' or 'matrix' hybridises preferentially to gene-poor regions of the genome (G-bands). Conversely, fractions attached to the nuclear 'skeleton' hybridise preferentially to gene-rich R-bands and sites of high levels of transcription. The inactive X chromosome has a deficit of associations with the nuclear skeleton but not with the matrix or scaffold. A large excess of attached sequences is found at some sites of constitutive heterochromatin, but not at centromeres.

Cell Nucleus↗
PubMed1997

Committed contracts: what happens after you take the pledge?

For years, hospitals played under shifting rules at the high-stakes purchasing table. Manufacturers, groups and providers all dealt and bluffed. Each made commitments to one another, but afterward the manufacturers would try to go in the back door if a competitor shut them out at the front, and hospitals would join multiple groups and shift loyalties at will to get the lowest price. Sure, all agreed that solid contract commitments would be better for everyone. But when it was time to ante up, what really mattered to each was getting the best deal. And "best" meant something different to each player.

Consumer Behavior↗
PubMed1995

A possible screening test for inherited p53-related defects based on the apoptotic response of peripheral blood lymphocytes to DNA damage.

The cellular response, in terms of cell cycle arrest(s) and apoptosis, to radiation-induced DNA damage was studied. Experiments were performed on both mitogen-stimulated and resting peripheral blood lymphocytes (PBLs) from normal and cancer-prone (C-P) individuals. The C-P individuals comprised three patients carrying germline p53 mutations and three members of two families apparently without such mutations, but with an inherited defect which results in p53 deregulation as shown by high levels of stabilised p53 protein in normal tissues. Interestingly, mitogen-stimulated PBL, from both normal and C-P individuals failed to demonstrate a G1 arrest after gamma radiation. However, a clear difference was seen in the apoptotic response to DNA damage, of PBL from normal and C-P individuals; PBLs from C-P individuals with inherited p53-related defects had a reduced apoptotic response (P = 0.0003). There was a wide margin of separation, with no overlap between the two groups, supporting the possibility of using this altered apoptotic response as a screening test. This simple and rapid procedure could be used to identify those individuals in a C-P family who carry germline p53-related defects. The method appears to detect both individuals with p53 mutations and those apparently without mutations but with other p53-related defects.

Adult↗