PubMed Health⌕ Search

Biomedical subjects

A Harrington

Publications and source records attributed to A Harrington.

At least 19 recordsLinked to original sources
PubMed2001

IpaC from Shigella and SipC from Salmonella possess similar biochemical properties but are functionally distinct.

Invasion plasmid antigen C (IpaC) is secreted via the type III secretion system (TTSS) of Shigella flexneri and serves as an essential effector molecule for epithelial cell invasion. The only homologue of IpaC identified thus far is Salmonella invasion protein C (SipC/SspC), which is essential for enterocyte invasion by Salmonella typhimurium. To explore the biochemical and functional relatedness of IpaC and SipC, recombinant derivatives of both proteins were purified so that their in vitro biochemical properties could be compared. Both proteins were found to: (i) enhance the entry of wild-type S. flexneri and S. typhimurium into cultured cells; (ii) interact with phospholipid membranes; and (iii) oligomerize in solution; however, IpaC appeared to be more efficient in carrying out several of the biochemical properties examined. Overall, the data indicate that purified IpaC and SipC are biochemically similar, although not identical with respect to their in vitro activities. To extend these observations, complementation analyses were conducted using S. flexneri SF621 and S. typhimurium SB220, neither of which is capable of invading epithelial cells because of non-polar null mutations in ipaC and sipC respectively. Interestingly, both ipaC and sipC restored invasiveness to SB220 whereas only ipaC restored invasiveness to SF621, suggesting that SipC lacks an activity possessed by IpaC. This functional difference is not at the level of secretion because IpaC and SipC are both secreted by SF621 and it does not appear to be because of SipC dependency on this native chaperone as coexpression of sipC and sicA in SF621 still failed to restore detectable invasiveness. Taken together, the data suggest that IpaC and SipC differ in either their ability to be translocated into host cells or in their function as effectors of host cell invasion. Because IpaB shares significant sequence homology with the YopB translocator of Yersinia species, the ability for IpaC and SipC to associate with this protein was explored as a potential indicator of translocation function. Both proteins were found to bind to purified IpaB with an apparent dissociation constant in the nanomolar range, suggesting that they may differ with respect to effector function. Interestingly, whereas SB220 expressing sipC behaved like wild-type Salmonella, in that it remained within its membrane-bound vacuole following entry into host cells, SB220 expressing ipaC was found in the cytoplasm of host cells. This observation indicates that IpaC and SipC are responsible for a major difference in the invasion strategies of Shigella and Salmonella, that is, they escape into the host cell cytoplasm. The implications of the role of each protein's biochemistry relative to its in vivo function is discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Ras pathway signals are required for notch-mediated oncogenesis.

The Notch genes of C. elegans, Drosophila melanogaster and vertebrates encode receptors responsible for cell fate decisions during development. These Notch receptors and their ligands, Delta and Jagged, have been implicated in several human diseases. Truncated, constitutively active mutant forms of the Notch receptor appear to be involved in human T-cell leukemia, mammary carcinomas in mice, and a tumorous germline phenotype in C. elegans. Since activated Notch induces solitary tumors in transgenic mice, it is highly likely that collaborating genetic events are required for tumor formation. We have assessed four signal transduction pathways to determine which might play additional roles in malignant transformation in concert with activated Notch4. Our results suggest that transformation by Notch does not, as might have been expected, depend on the Src-like kinases Lck and Fyn, nor upon signals from protein kinase A and C (PKA, PKC). Rather, transformation by Notch requires active signals from the Erk/MAP kinase and PI-3 kinase pathways downstream of Ras. Oncogene (2000) 19, 4191 - 4198

Animals↗
PubMed1999

The effects of amperozide on cocaine-induced social withdrawal in rats.

Cocaine decreases social interactions in both humans and animals, but it is not known whether the drugged animal withdraws from an undrugged conspecific, the undrugged conspecific avoids the drugged animal, or a combination of these two factors occurs. In the first experiment, the source of cocaine-induced social withdrawal was determined using a tether paradigm, in which the movement of one of the rats was restricted to one half of the observation chamber, such that the freely moving rat had the option of escaping social interactions. There were decreases in social interactions in the condition in which both rats were freely moving, and in the condition in which the undrugged rat was tethered, but not when the drugged rat was tethered and could not escape social contact. A second experiment was conducted to test the efficacy of the potent serotonin receptor antagonist, amperozide, in attenuating cocaine-induced social withdrawal using the condition in which the drugged rat was freely moving. Either amperozide (1.0, 3.0, and 5.0 mg/kg) or saline vehicle was injected into rats 1 h before receiving a 30.0 mg/kg cocaine dose. Cocaine decreased social interactions. Amperozide restored social interactions to near control levels and elevated social interactions in the animals treated with saline vehicle.

Animals↗
PubMed1999

Dlx-5 in limb initiation in the chick embryo.

Dlx-5 is a vertebrate homolog of the Drosophila Distal-less gene, one of the first genetic signals for limb formation in the fly. In the present study we have explored the possible role of Dlx-5 in limb initiation in the chick embryo. At stage 14 which is well before the initial formation of limb buds Dlx-5 is highly and specifically expressed in the ectoderm of the presumptive wing and leg forming regions of the lateral plate, but not in the intervening non-limb forming prospective flank. Thus, Dlx-5 expression distinguishes the limb-forming territories prior to limb budding, and is one of the first molecular markers of vertebrate limb initiation. Furthermore, Dlx-5 expression is induced in the non-limb-forming flank within 12 hours after implantation of an FGF2-soaked bead, a procedure that results in the induction of an ectopic limb. The rapid induction of Dlx-5 expression in response to a signal which ultimately leads to supernumerary limb formation is consistent with a role for Dlx-5 in limb initiation. We have also examined the expression of Dlx-5 in the limb buds of amelic limbless mutant chick embryos, which undergo normal limb formation but do not form an AER and thus fail to undergo further outgrowth. Dlx-5 is transiently expressed by the ectoderm of emergent limbless limb buds, consistent with a role for Dlx-5 in limb initiation. Together, our results suggest that Dlx-5 may be involved in the specification of the limb territories of the lateral plate, and in the initial formation of the limb bud from these regions. Dev Dyn 1999;216:10-15.

Animals↗
PubMed1998

Patterns of X chromosome inactivation in sporadic basal cell carcinomas: evidence for clonality.

BACKGROUND: Some basal cell carcinomas (BCCs) contain genetic mutations, suggesting that the lesion is composed of a monoclonal population of cells. Clonality, a distinguishing feature of neoplasia, can be inferred by referencing clonal markers such as the pattern of X chromosome inactivation. The X-linked human androgen receptor gene (HUMARA; GenBank) contains a polymorphic DNA marker that reliably illustrates the pattern of X chromosome inactivation in a tissue. OBJECTIVE: Our purpose was to determine the clonality of sporadic BCCs by examining patterns of X chromosome inactivation. METHODS: The patterns of X chromosome inactivation in paired samples of normal skin and sporadic BCCs from 24 women were compared by means of the HUMARA gene assay. RESULTS: All samples from normal skin displayed random X chromosome inactivation, consistent with lyonization. In 15 of 25 tumor samples (60%), nonrandom X chromosome inactivation was detected, consistent with monoclonality. CONCLUSION: At least some sporadic BCCs are composed of a monoclonal population of cells, strengthening the contention that a collection of mutations confers a growth advantage to this epithelial lesion.

Adult↗
PubMed1998

Reconceptualizing rigour: the case for reflexivity.

This paper is a critical review of recent discussions of rigour in nursing research. We will argue that 'borrowing' evaluation criteria from one paradigm of inquiry and applying them to another is problematic. We attempt to map the 'rigour' field and add a dimension to the existing debate about rigour and qualitative research through inclusion of reflexivity guided by philosophical hermeneutics. We describe reflexivity and appeal to writers to incorporate a reflexive account into their research product by signposting to readers 'what is going on' while researching. We contend that researchers bring to the research product, data generated, a range of literature, a positioning of this literature, a positioning of oneself, and moral socio-political contexts. We suggest that reflexive research is characterized by ongoing self-critique and self-appraisal and that the research product can be given shape by the politics of location and positioning. We emphasize that in the creation of a text (the research product) it is desirable that the researcher be a skilled writer. Finally we claim that if the research product is well signposted, the readers will be able to travel easily through the worlds of the participants and makers of the text (the researchers) and decide for themselves whether the text is believable or plausible (our terms for rigour).

Australia↗
PubMed1996

The effects of raclopride on vacuous jaw movements in rats following acute administration.

Classic neuroleptics produce a syndrome of vacuous jaw movements in rats, whereas atypical neuroleptics like clozapine do not. The present study compared the effects of repeated administration of raclopride, clozapine, haloperidol, or vehicle on vacuous jaw movements in rats over a 4-week period. Rats received an IP injection of drug once a day. On days 1, 8, 15, and 29 the rats were observed for a 5-min period by two trained observers who recorded their vacuous jaw movements. The dose-response curves at which each drug produced vacuous jaw movements are presented and discussed in terms of their predictive capabilities of early onset extrapyramidal side effects.

Animals↗
PubMed1996

Clonality of basal cell carcinoma--molecular analysis of an interesting case.

Tumor cells represent a single clone of cells that have undergone a series of mutations in genomic DNA. This process, known as clonal evolution, is a distinguishing feature of cancer. The human androgen receptor gene (HUMARA; GenBank) contains a highly polymorphic cytosine-adenine-guanine trinucleotide repeat that can be used to determine clonality by depicting X chromosome inactivation patterns. Random X chromosome inactivation is consistent with polyclonality; nonrandom X chromosome inactivation indicates a clonal population of cells. Basal cell carcinoma (BCC) demonstrates an atypical growth pattern in that it grows slowly, rarely metastasizes, and is rarely lethal. Whether this tumor results from the accumulation of mutations in a single cell with subsequent clonal expansion or reflects a polyclonal response by a group of cells to a growth stimulus is unknown. To provide further insight into the molecular events characterizing BCCs, we determined the clonal origin of five modular BCCs from a female patient by analyzing X chromosome inactivation patterns at the HUMARA locus. All tumors demonstrated a nonrandom pattern of X chromosome inactivation, consistent with monoclonal proliferation. These findings provide strong genetic evidence that sporadic BCCs develop by clonal evolution and support the contention that a series of mutations in a single cell is responsible for the altered growth state seen in these transformed epithelial cells.

Aged↗
PubMed1996

The effects of cyproheptadine on vacuous jaw movements in rats: a comparison with haloperidol and clozapine.

Classic neuroleptics produce a syndrome of vacuous jaw movements in rats, but atypical neuroleptics such as clozapine do not. This syndrome has been offered as a rapid and inexpensive means of assaying novel antipsychotic compounds for the production of early onset extrapyramidal side effects. Cyproheptadine is a serotonergic antagonist that has been suggested for the treatment of schizophrenia. The present study compared the effects of repeated administration of cyproheptadine with those of the classic antipsychotic haloperidol and the atypical antipsychotic clozapine in terms of their production of vacuous jaw movements. Rats were administered either tartaric acid vehicle or one of three doses of each drug daily for a month. Once a week the rats were observed for a 5-minute period by two trained observers who recorded their vacuous jaw movements. Cyproheptadine produced elevations in vacuous jaw movements similar to those produced by haloperidol, but clozapine did not. These results indicate that cyproheptadine may be similar to classic antipsychotics in the production of extrapyramidal symptoms in humans, and they underscore the usefulness of vacuous jaw movement model of early onset extrapyramidal side effects.

Animals↗
PubMed1995

Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk.

Polycyclic aromatic hydrocarbons, possible human breast carcinogens, are metabolized by cytochrome P4501A1 (CYP1A1) and glutathione S-transferase (GSTM1). A CYP1A1 polymorphism (isoleucine to valine substitution in exon 7) or the null allele for GSTM1 may affect the mutagenic potential of polycyclic aromatic hydrocarbons. We examined polymorphisms in GSTM1 and CYP1A1 in relation to breast cancer risk. Included were 216 postmenopausal Caucasian women with incident breast cancer and 282 community controls. DNA analyses suggested no increased breast cancer risk with the null GSTM1 genotype [odds ratio (OR) = 1.10; CI, 0.73-1.64], although there was some indication that the null genotype was associated with risk among the youngest postmenopausal women (OR = 2.44; CI, 0.89-6.64). Slightly elevated risk was associated with the CYP1A1 polymorphism (OR = 1.61; CI, 0.94-2.75) and was highest for those who smoked up to 29 pack-years (OR = 5.22; CI, 1.16-23.56). Statistical power to detect an effect may be limited by small numbers, and larger sample sizes would be required to corroborate these suggestive findings.

Age Factors↗
PubMed1995

Characterization of plasmid-encoded citrate permease (citP) genes from Leuconostoc species reveals high sequence conservation with the Lactococcus lactis citP gene.

The citrate permease determinant (citP) in several Leuconostoc strains was demonstrated to be plasmid encoded by curing experiments and hybridization studies with a DNA fragment containing the citP gene from Lactococcus lactis subsp. lactis biovar diacetylactis NCDO176. Cloning and nucleotide sequence analysis of Leuconostoc lactis NZ6070 citP revealed almost complete identity to lactococcal citP.

Amino Acid Sequence↗
PubMed1995

Spiritual care: what does it mean to RNs?

The purpose of this descriptive study was to discover the meanings that two groups of registered nurses ascribed to the word 'spirit' and its derivatives. The study also examined the nurses' perceptions of the nature of spiritual nursing, the status of spiritual care in relation to 'normal' nursing care and the adequacy of nursing education as preparation for providing spiritual care. Data were gathered from audio-taped interviews with 10 registered nurses who worked in one hospice and 10 who worked in a variety of acute care settings. The participants were asked four open-ended questions and from their responses 29 themes emerged which led to the construction of a model which shows that the nurses delivering spiritual care are influenced by their practice settings and nursing education which together impact on the quality of spiritual care. The elements of the model are discussed and recommendations that flow from the findings are made.

Acute Disease↗
PubMed1994

Nucleotide sequence and structural organization of the small, broad-host-range plasmid pCI411 from Leuconostoc lactis 533.

The nucleotide sequence of the Leuconostoc lactis 533 cryptic plasmid pCI411 (2926 bp) was determined. Analysis revealed the presence of three open reading frames (ORFs). ORF 1 was capable of encoding a 24.9 kDa peptide which shared homology with the replication initiation protein (RepB) from a number of Gram-positive rolling circle plasmids. ORF 2 could encode a peptide of 6.6 kDa which was homologous to the RepC protein of the lactococcal plasmid pWV01. A function could not be assigned to ORF 3, which was capable of encoding a 12.1 kDa peptide. Transcription-translation analysis indicated the presence of three peptides of the predicted molecular masses. A putative double strand origin of replication (DSO) was identified which showed strong similarity with the DSO of a number of Gram-positive plasmids including pE194 from Staphylococcus. Structural analysis identified a number of direct and indirect repeats in addition to putative recombination-specific sites (RSA and RSB) in the non-coding region of pCI411. The observed characteristics suggest that this plasmid replicates using the rolling circle mechanism. pCI411, which could be introduced into Leuconostoc, Lactococcus, Streptococcus, Lactobacillus and Bacillus is the first plasmid from the genus Leuconostoc to be characterized in such detail.

Amino Acid Sequence↗
PubMed1993

Clonal origin of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a malignant tumor originating in the dermis. Although it is known to be locally aggressive, it only rarely metastasizes and will recur unless completely excised. The exact cell responsible for the development of a DFSP has been a matter of controversy for several decades; however, most histochemical and electron microscopic studies support a fibroblastic origin, with the tumor cells staining uniformly for vimentin and containing active endoplasmic reticulum synthesizing collagen. Cytogenetic analysis of some of these tumors has demonstrated at least two specific chromosomal abnormalities in DFSP and suggested that this tumor may be polyclonal in origin. To further address the clonal origin of this locally invasive, mesenchymal tumor, we analyzed DNA from two female patients by restriction fragment length polymorphisms and methylation analysis. Our data strongly support the concept that DFSP is monoclonal in origin and that this tumor mass reflects the clonal expansion of a single cell.

Adult↗
PubMed1992

Plasmid involvement in the formation of a spontaneous bacteriophage insensitive mutant of Lactococcus lactis.

Lactococcus lactis subsp. lactis biovar. diacetylactis DPC721 is a spontaneous bacteriophage insensitive mutant of strain DPC220, isolated after challenge with an industrial bacteriophage, phi D1. Plasmid analysis demonstrated that the bacteriophage insensitivity was associated with the absence of two native DPC220 plasmids (pAH82 and pAH33), and the presence of a novel plasmid (pAH90) in DPC721. The plasmids were transferred by conjugative mobilization to a plasmid free background where it was confirmed by restriction mapping that pAH90 is a co-integrate formed by the precise recombination of pAH82 and pAH33. The resistance phenotype encoded by pAH90 was also active against two bacteriophage homologous for the plasmid-free strain. Plasmid pAH90 was shown to encode at least two independent resistance mechanisms, including an adsorption-inhibition mechanism and a restriction and modification system. The adsorption-inhibition mechanism encoded by the co-integrate plasmid was specific for one of the phage used in this study.

Bacteriophages↗