PubMed Health⌕ Search

Biomedical subjects

R Neill

Publications and source records attributed to R Neill.

15 recordsLinked to original sources
PubMed2001

Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues.

PURPOSE: Fatty acid-binding protein (FABP) expression patterns were evaluated as potential markers and therapeutic targets for prostate cancer. EXPERIMENTAL DESIGN: FABP expression levels were determined by reverse transcription-PCR in cultured prostate normal and tumor cells and in human biopsy samples. Regulation of cellular processes was examined using FABP antisense constructs. RESULTS: Prostate cells express a variety of different FABPs. Liver (L)- and intestine-FABPs were elevated 5-9-fold in prostate cancer compared with normal primary prostate cells. In contrast, adipose- and epidermal-FABPs were markedly down-regulated (3-20-fold) in cancer versus normal cells. Similar expression patterns were found in human tissue biopsy samples. However, brain-FABP had a distinct pattern of expression: it was overexpressed only in LNCaP cells and in well-differentiated tissue samples, suggesting a stage-specific expression profile. Secretion of L-FABP protein was observed from DU 145 prostate cancer cells, but not in the culture fluid of normal prostate epithelial cells. Antisense oligodeoxynucleotides, designed to block production of epidermal-FABP (a marker for normal prostate cells), caused increased proliferation in DU 145 prostate cancer cells. In vivid contrast, antisense oligodeoxynucleotides to L-FABP (overexpressed in prostate cancer) decreased proliferation and caused apoptosis. CONCLUSIONS: We propose that there is a distinct balance between these groups of FABPs, whose altered regulation in cells may play a role in prostate cancer. Furthermore, the pattern of expression and secretion of FABPs have the potential to serve as a diagnostic marker for an aggressive phenotype of prostate cancer.

Apoptosis↗
PubMed1999

Production of tumor necrosis factor alpha in human T lymphocytes by staphylococcal enterotoxin B correlates with toxin-induced proliferation and is regulated through protein kinase C.

The superantigen staphylococcal enterotoxin B (SEB) simultaneously binds both the major histocompatibility complex (MHC) class II receptor on monocytes and the T-cell receptor (TCR) on T lymphocytes, resulting in a range of cell responses including induction of tumor necrosis factor alpha (TNF-alpha). In this study, we have used mixed cultures of human peripheral blood monocytes and lymphocytes to investigate biochemical events controlling SEB induction of TNF-alpha. TNF-alpha production induced by SEB in mixed cultures is more closely associated with T cells than with monocytes: (i) a TCR-binding-site mutant of SEB (N23F) is less active in TNF-alpha induction than an MHC class II receptor-binding-site mutant (F44R), and (ii) flow cytometric analysis indicated that SEB induced TNF-alpha production in T cells but not in monocytes. Pretreatment of cells with inhibitors of signal transduction pathways was employed to further define events in SEB-induced TNF-alpha production. Neither protein kinase A inhibitors nor two protein tyrosine kinase inhibitors altered SEB-induced TNF-alpha production. In contrast, SEB induced protein kinase C (PKC) translocation, and pretreatment of cultures with inhibitors of PKC blocked TNF-alpha induction. Alteration of levels of diacylglycerol (DAG), an activator of PKC, by treatment with inhibitors of phospholipase C or DAG kinase also altered SEB-induced TNF-alpha production. These data suggest that PKC activation plays a critical role in SEB-induced TNF-alpha production in human T cells.

Cells, Cultured↗
PubMed1995

Epidemiology and molecular characterisation of toxigenic Corynebacterium diphtheriae var mitis from a case of cutaneous diphtheria in Manchester.

Diphtheria is now an uncommon disease in Britain. We describe an imported case of cutaneous diphtheria in a previously immunised adult cause by C. diphtheriae var mitis. The control measures adopted to deal with the index case and two secondary cases so as to limit further spread among household and school contacts are outlined. Molecular typing was used to study the mode of spread of the organism among contacts.

Adult↗
PubMed1994

Role of Shiga-like toxin I in bacterial enteritis: comparison between isogenic Escherichia coli strains induced in rabbits.

BACKGROUND/AIMS: Enteroadherent Escherichia coli that produce Shiga-like toxins are important causes of human disease, including enterohemorrhagic E. coli-induced colitis (EHEC). The role of Shiga-like toxins in these illnesses is unclear. The aim of this study was to establish an animal model for human EHEC and to determine the role of Shiga-like toxin I (SLT-I) in this model. METHODS: E. coli strain RDEC-1 is an enteroadherent rabbit diarrheal pathogen. An isogenic variant of RDEC-1 (termed RDEC-H19A) producing high levels of SLT-I was obtained by infecting RDEC-1 with an SLT-I-converting bacteriophage. The effects of in vivo enteric infection produced in rabbits by RDEC-H19A were compared with those in uninfected and RDEC-1-infected animals. RESULTS: SLT-I-producing RDEC-H19A induced a severe, noninvasive, enteroadherent infection in rabbits. Clinically, infection with RDEC-H19A was more severe than infection with RDEC-1 and caused more serious histological lesions including vascular changes, edema, and more severe inflammation. Interleukin 1 and platelet-activating factor appear to be important inflammatory mediators to this infection. CONCLUSIONS: The illness induced by RDEC-H19A in rabbits resembled enterohemorrhagic E. coli-induced colitis of humans. SLT-I is an important virulence factor in the pathogenesis of EHEC.

Animals↗
PubMed1994

Identification of staphylococcal enterotoxin B sequences important for induction of lymphocyte proliferation by using synthetic peptide fragments of the toxin.

A series of 13 synthetic peptides, approximately 30 amino acids each, which spanned the entire sequence of staphylococcal enterotoxin B (SEB) were tested to evaluate their effects on T-cell proliferation in a culture system containing elutriated human peripheral blood lymphocytes incubated with a specific ratio of mononuclear cells. Four peptide regions were found to inhibit SEB-induced proliferation; they included sequences 1 to 30 (previously thought to be involved in major histocompatibility complex class II binding), 61 to 92 (sequences which relate to the T-cell receptor site), 93 to 112 (a linear sequence corresponding to the cysteine loop), and 130 to 160 (containing a highly conserved sequence, KKKVTAQEL). Antisera raised to this last peptide were capable of neutralizing SEB-induced proliferation. Antisera raised against the peptides which overlapped this sequence also were somewhat inhibitory. Neutralizing antisera were not produced from any other peptide sequence tested. To determine if any of these effects were nonspecific with regard to SEB-induced proliferation, the peptides were tested for inhibition of phorbol dibutyryl ester-induced proliferation, and only the sequence 93 to 112 (corresponding to the cysteinyl loop region) was consistently inhibitory (40%). Of the regions which displayed inhibition of SEB-induced proliferation, the peptide 130 to 160 inhibited binding of 125I-SEB to lymphocytes. These data suggest that the residues containing and surrounding the sequence KKKVTAQEL may be critical in the SEB-induced proliferation and may be useful for developing neutralizing antisera to SEB.

Amino Acid Sequence↗
PubMed1990

Regulation of the relative abundances of c-myc mRNAs in human promyelocytic HL60 cells.

Transcription of the c-myc gene is initiated mainly from two promoters, P1 and P2. By S1 nuclease analysis we found that there is 8 times more P2- than P1-initiated RNA in total RNA from HL60 cells. The half-lives of P1- and P2-initiated transcripts are 26 and 18 min, respectively, so the difference in the relative abundance of the mRNAs is not due to differences in their stabilities. The relative rates of transcription from the P1 and P2 promoters, estimated by in vitro nuclear run-on analysis, were found to differ by about 10-fold, sufficient to account for the difference in the steady-state levels of the two mRNAs. The abundance of c-myc mRNA changes dramatically during differentiation of HL60 cells. Dimethyl sulphoxide causes a very rapid reduction in total c-myc mRNA, while with phorbol ester a transient increase occurs followed by a more gradual decline. At no time during these dramatic alterations were significant changes detected in the relative abundance of P1- and P2-initiated mRNAs, or in their stabilities.

Cell Transformation, Neoplastic↗
PubMed1990

Staphylococcus aureus enterotoxin B challenge of monkeys: correlation of plasma levels of arachidonic acid cascade products with occurrence of illness.

Arachidonic acid cascade products have been shown to be increased in vitro in Staphylococcus aureus enterotoxin B (SEB)-treated epithelial cell cultures in our laboratory. In order to confirm that these products were clinically related to SEB intoxication, monkeys were administered SEB by nasogastric intubation. It caused emesis in five of six monkeys (less than 4 h), and the sixth monkey showed signs of mild illness. The monkeys which vomited continued to display signs of gastrointestinal illness beyond 8 h but were without any apparent signs of illness by 24 h. Blood samples were collected prior to SEB administration, upon first indication of illness, and at twice that time interval. One week prior to SEB treatment, the same monkeys were administered saline by nasogastric intubation and in every way handled similarly in order to serve as their own controls. Blood samples were taken from the control animals at 0, 4, and 8 h. The plasma concentrations of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE) did not vary significantly throughout the 8-h experiment for saline-treated controls, nor did they differ from the concentrations found in the plasma of monkeys just before administration of SEB. When the SEB-treated monkeys showed the first indication of illness (less than 4 h), the mean of the concentration in plasma of PGE2 increased 1.44-fold, that of LTB4 increased 2.23-fold, and that of 5-HETE was essentially unchanged. At twice the time interval of the first display of illness (less than 8 h), PGE2 was still elevated (1.48-fold), LTB4 had decreased slightly to 1.66-fold, and 5-HETE had soared (3,45-fold), suggesting a divergence in the enzymatic utilization of the parent compound of the latter two metabolites, 5-hydroperoxyeicosatetraenoic acid. These studies suggest that arachidonic acid cascade metabolites were a consequence of SEB intoxication and may provide a logical site for metabolic interference in SEB-induced toxicity.

Animals↗
PubMed1989

An attempt to select pseudonormal revertants of Friend erythroleukaemia cells using cytochalasin B.

Treatment of Friend erythroleukaemia cells with cytochalasin B (CB) resulted in multinucleation and loss of viability characteristic of a virus-transformed cell line. In an attempt to isolate pseudonormal revertants of this cell line mutagenized cultures were exposed to CB and surviving clones isolated. Many of these were found to be mutants resistant to the growth inhibitory effects of CB. The proportion of such mutants was reduced by simultaneous selection in CB and cytosine arabinoside. Of 699 clones examined none consistently exhibited reduced levels of multinucleation in the presence of CB. The inability of CB to select for revertants displaying a phenotype closer to normal cells is discussed.

Animals↗
PubMed1989

Responses of patient, their relatives and professionals to a "home-grown" videotape course on schizophrenia.

The Richmond Mental Health Team of the Greater Vancouver Mental Health Service produced a low-cost, 4-1/2 hour videotape course on schizophrenia using a multidisciplinary panel of team staff and an audience of patients, family members and community groups. The resource people interviewed were from the local area. An interview of a sample of recipients of the videotape course revealed that patient and family understanding of the illness, its treatment and the service delivery system had been elementary before the course. The program improved this understanding and reportedly reduced family conflict in certain areas. Professional consumers were generally pleased with the content and format of the video, but were dissatisfied with the technical quality. Although it was designed for use with patient and family groups in community mental health settings, professional recipients were using the videotape primarily to train staff and paraprofessionals. The manual that accompanied the videotape was seldom used. Given the cost effectiveness of using videotape to design psycho-educational programs, its potentially wide distribution, the staff development spin-offs and its community development applications, we encourage provincial and state services to produce their own videotape programs.

Adult↗
PubMed1986

Global stereopsis in stroke patients.

Contradictory evidence has been presented in the literature on the existence of a right-hemisphere mechanism subserving global stereopsis. In the present study evoked responses to dynamic random-dot stereograms were recorded from International 10-20 scalp sites O2, P4, T6, T4 and homotopic sites over the left hemisphere. Stroke patients with unilateral lesions were selected on the basis of satisfactory performance on ocular screening tests and on clinical or objective indications that dementia was absent. Control subjects were found among the relatives of patients. The stereopsis test schedule included left, right and centre field presentations of 30 arc min, disparities. The dot density of the disparity, relative to that of the remainder of the random dot field, was manipulated to provide a full contrast stimulus and a no-contrast uniform field stimulus, thus varying the availability of monocular cues provided by the contrast factor. Latency and amplitude of the evoked potentials were computed and submitted to analyses of variance. No significant results were found which supported the proposition of a lateralized mechanism for global stereopsis. This conclusion is in conflict with the findings of some earlier reports. It is suggested that the techniques used in the earlier experiments may not have been adequate for the study of the questions involved.

Aged↗
PubMed1985

Effect of cytochalasin B on somatic cell hybrids between normal and transformed cells.

Cytochalasin B (CB) prevents cytokinesis in animal cells. In normal cells nuclear division and DNA synthesis are also blocked and the cells, held in the G1 phase of the cell cycle, remain either mononucleate or binucleate. In transformed cell lines DNA synthesis and nuclear division continue and the cells become multinucleate. We have examined the response to CB in two sets of somatic cell hybrids made between cells that display multinucleation after CB treatment and cells that do not. In a cross between transformed mouse LMTK cells and normal rat embryo lung cells, very little multinucleation was observed after treatment with CB for 7 days. The ability of the LMTK cells to form clones in soft agar was also significantly reduced in these hybrids. Segregant sub-clones that re-expressed both of these transformation phenotypes were isolated. These had reduced chromosome numbers. A second cross was made between two variants of the BHK cell line, one of which displayed a high level of multinucleation in CB while the other did not. Again the hybrids showed a response similar to that of the non-multinucleating parent. From the results obtained with these two hybrids we conclude that the multinucleation induced in transformed cells by CB behaves as a recessive character in crosses with normal cells.

Animals↗