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Biomedical subjects

N Oliver

Publications and source records attributed to N Oliver.

At least 19 recordsLinked to original sources
PubMed2006

Connective tissue growth factor/CCN2 overexpression in mouse synovial lining results in transient fibrosis and cartilage damage.

OBJECTIVE: Characteristics of osteoarthritis (OA) include cartilage damage, fibrosis, and osteophyte formation. Connective tissue growth factor (CTGF; also known as CCN2), is found in high levels in OA chondrocytes and is frequently involved in fibrosis, bone formation, and cartilage repair. The present study was therefore undertaken to investigate the potential role of CTGF in OA pathophysiology. METHODS: We transfected the synovial lining of mouse knee joints with a recombinant adenovirus expressing human CTGF and measured synovial fibrosis and proteoglycan content in cartilage on days 1, 3, 7, 14, and 28. Messenger RNA (mRNA) expression in synovium and cartilage was measured on days 3, 7, and 21. RESULTS: CTGF induced synovial fibrosis, as indicated by accumulation of extracellular matrix and an increase in procollagen type I-positive cells. The fibrosis reached a maximum on day 7 and had reversed by day 28. Levels of mRNA for matrix metalloproteinase 3 (MMP-3), MMP-13, ADAMTS-4, ADAMTS-5, tissue inhibitor of metalloproteinases 1 (TIMP-1), and transforming growth factor beta were elevated in the fibrotic tissue. TIMP-1 expression was elevated on day 3, while expression of other genes did not increase until day 7 or later. CTGF induced proteoglycan depletion in cartilage as early as day 1. Maximal depletion was observed on days 3-7. Cartilage damage was reduced by day 28. A high level of MMP-3 mRNA expression was found in cartilage. CTGF overexpression did not induce osteophyte formation. CONCLUSION: CTGF induces transient fibrosis that is reversible within 28 days. Overexpression of CTGF in knee joints results in reversible cartilage damage, induced either by the high CTGF levels or via factors produced by the CTGF-induced fibrotic tissue.

Animals↗
PubMed2005

Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome.

BACKGROUND/AIMS: Pseudoexfoliation syndrome (PXF) was recently found to be associated with increased expression of transforming growth factor beta(1) (TGFbeta(1)) in the aqueous humour. As concern has been raised regarding anti-TGFbeta therapy, which can potentially disrupt the maintenance of anterior chamber associated immune deviation, the authors explored the levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF) in aqueous humour to determine if these may represent alternative therapeutic targets. METHODS: Aqueous humour samples were collected from patients who underwent routine cataract surgery. All patients were categorised into three main groups-PXF, uveitis, and control. The PXF group was further subcategorised into three grades based on the density of the exfoliative material observed on biomicroscopy, as well as the presence or absence of glaucoma. TIMP-1, MMP-9, and CTGF levels were measured using specific enzyme immunoassays (ELISA). RESULTS: Eyes with PXF had significantly higher aqueous humour TIMP-1 concentration (n = 56, mean (SE), 9.76 (1.10) ng/ml) compared with controls (n = 112, 5.73 (0.43) ng/ml, p<0.01). Similarly, the CTGF level in PXF eyes (n = 36, 4.38 (0.65) ng/ml) was higher than controls (n = 29, 2.35 (0.46) ng/ml, p<0.05). Further, the CTGF concentration in the PXF glaucoma group is significantly higher compared with PXF eyes without glaucoma (6.03 (1.09) ng/ml v 2.73 (0.45) ng/ml, p<0.01). The MMP-9 levels were low and below detection limit in all PXF and control samples with no statistical difference between groups. CONCLUSION: A raised TIMP-1 level and a low MMP-9 level in aqueous humour of PXF eyes may imply a downregulation in proteolytic activity. The increased CTGF concentration supports the proposed fibrotic pathology of PXF. Regulation of MMP/TIMP expression and anti-CTGF therapy may offer potential therapeutic avenues for controlling PXF associated ocular morbidity.

Aged↗
PubMed2004

Differential expression of connective tissue growth factor in microglia and pericytes in the human diabetic retina.

BACKGROUND/AIM: Connective tissue growth factor (CTGF) stimulates extracellular matrix formation, fibrosis, and angiogenesis. It has a role in the pathogenesis of diabetic nephropathy and possibly in diabetic retinopathy (DR): in cultured retinal vascular cells CTGF is induced by VEGF-A. To further characterise this role the authors investigated CTGF expression in normal and diabetic human retina. METHODS: CTGF expression patterns were studied by immunohistochemistry in the retina of eyes of 36 diabetic persons and 18 non-diabetic controls and compared with markers of endothelial cells (CD31, PAL-E), pericytes (NG2), astrocytes (GFAP), and microglia (CD45). RESULTS: In the retina, distinct and specific staining of CTGF was observed in microglia, situated around or in close vicinity of retinal capillaries. In the control cases, sporadic staining of pericytes was also observed within the vascular wall. In contrast, in the retina of people with diabetes, CTGF staining in microglia was decreased and staining in pericytes was increased. This pattern of predominantly pericyte staining was observed in 20 out of 36 diabetic cases and in one out of 18 controls. The altered CTGF staining patterns in the diabetic cases did not correlate to staining of PAL-E, a marker of retinal vascular leakage associated with DR. CONCLUSIONS: The study shows that CTGF is expressed in microglia in the normal retina whereas in a large subset of diabetic persons, CTGF expression shifts to microvascular pericytes. This altered CTGF expression pattern appears unrelated to manifest DR and may therefore represent a preclinical retinal change caused by diabetes. The results suggest a distinct, but as yet unidentified, role of CTGF in the pathogenesis of diabetic retinopathy.

Aged↗
PubMed2001

Resistance studies with daptomycin.

We studied the in vitro emergence of resistance to daptomycin using three methods: spontaneous resistance incidence, serial passage in the presence of increasing drug concentrations, and chemical mutagenesis. No spontaneously resistant mutants were obtained for any organism tested (<10(-10) for Staphylococcus aureus, <10(-9) for Staphylococcus epidermidis, <10(-9) for Enterococcus faecalis, <10(-9) for Enterococcus faecium, <10(-8) for Streptococcus pneumoniae). Population analysis demonstrated that bacterial susceptibility to daptomycin is heterogeneous. Assay results were sensitive to calcium concentration and culture density, both of which can affect apparent resistance rates. Stable S. aureus mutants were isolated by both serial passage in liquid media and chemical mutagenesis. The daptomycin MICs for these isolates were 8- to 32-fold higher than for the parental strain. Many mutants with high MICs (>12.5 microg/ml) had significant growth defects but did not display phenotypes typical of S. aureus small colony variants. The voltage component (Delta psi) of the bacterial membrane potential was increased in three independent resistant isolates. In vivo data showed that some daptomycin-resistant mutants had lost significant virulence. For other mutants, the degree of in vitro resistance was greater than the change in in vivo susceptibility. These results suggest that infection with some daptomycin-resistant organisms may still be easily treatable.

Animals↗
PubMed2001

The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression.

BACKGROUND: Chronic vagus nerve stimulation (VNS) is effective in the management of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has clinically significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes. However, limited information regarding the effects of VNS on neurocognitive performance exists. OBJECTIVE: The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration. METHOD: A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS. Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor function, language, attention, memory, and executive function. RESULTS: No evidence of deterioration in any neurocognitive measure was detected. Relative to baseline, improvement in motor speed (finger tapping), psychomotor function (digit-symbol test), language (verbal fluency), and executive functions (logical reasoning, working memory, response inhibition, or impulsiveness) was found. For some measures, improved neurocognitive performance correlated with the extent of reduction in depressive symptoms, but VNS output current was not related to changes in cognitive performance. CONCLUSIONS: Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function, primarily among patients who show clinical improvement. Controlled investigation is needed to rule out the contribution of practice effects.

Adolescent↗
PubMed1999

Improvement of depression following transcranial magnetic stimulation.

Psychiatry as a field was transformed by the discovery and introduction of electroconvulsive therapy (ECT) as a treatment in the early part of this century. ECT demonstrated that depression was a disease of the brain and that it could be treated with a direct brain intervention. Psychiatry's evolution continued in 1958 with the discovery of the antidepressant activity of the monoamine oxidase inhibitors. Interestingly, although the area of neuropsychopharmacology has continued to advance, the realm of physical somatic interventions in psychiatry has lagged behind. With perhaps the exception of light therapy, there were no advances in somatic interventions in psychiatry. However, in 1985, Barker et al. developed a brief high intensity electromagnet capable of depolarizing cortical neurons, called transcranial magnetic stimulation (TMS). There has been much interest in the past 10 years in whether TMS might have antidepressant actions, similar to ECT but without causing a seizure and with no apparent cognitive side effects. This review examines the basic principles underlying TMS, and describes how TMS differs from electrical stimulation and the other uses of magnets.

Cerebral Cortex↗
PubMed1997

Case management: a week in the life of a clinical case management team.

This paper describes the work of a clinical case management core team (four nurses and an occupational therapist) during the course of a week. Information was gathered through non-participant observation of the team by two independent researchers. Transcripts produced from the data recorded were examined. From this, seven categories of activity were identified: planned client contact; unplanned client contact; family/carer contact; liaison; administration; team information sharing and supervision, training and personal development. These categories were felt to encompass the range of activities practised by the team. The amount of time that case managers spent engaged in these core functions was calculated. Detailed examples are presented. Results are discussed with reference to Kanter's components and principles of clinical case management.

Adult↗
PubMed1997

Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics.

In order to determine whether matrix metalloproteinases (MMPs) contribute to inflammation in asthma, we have examined the release of MMPs in bronchoalveolar lavage (BAL) fluids and their production and regulation by alveolar macrophages (AM), in short-term culture. BAL was collected from 38 asthmatic subjects (24 untreated and 14 treated with inhaled corticosteroids), 26 healthy nonsmokers, and 18 patients with chronic bronchitis used as a control group for another inflammation. The profile of MMPs present in BAL fluid and AM supernatant, determined by zymographic analysis, was found to be similar in all populations. The main enzyme released was identified immunologically as MMP-9, a potent collagenolytic and elastolytic enzyme. Its release, measured using enzyme immunoassay, was significantly enhanced in fluids and in AM supernatants from untreated asthmatics compared with those from the other populations. Enhanced MMP-9 levels, in asthma, could not be explained by a different sensitivity of AM to interleukin-4, interferon-gamma, or dexamethasone, compounds that have been shown to inhibit MMP-9. The phorbol ester phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, significantly increased MMP-9 in AM from healthy control subjects but not in those from untreated asthmatics. Calphostin C and H7, PKC inhibitors, significantly reduced PMA-stimulated MMP-9 release in AM from healthy control subjects and spontaneous MMP-9 release in AM from untreated asthmatics. H8, a PKA inhibitor, was inactive in both populations. These data suggest that the stimulation of MMP-9 release in AM from untreated asthmatic patients occurs, at least partly, via signals activating PKC.

Adolescent↗
PubMed1996

Stress and its relationship to expressed emotion in community mental health workers.

A small opportunistic study of Stress and Expressed Emotion was undertaken with community mental health workers, who were all case managers or keyworkers to clients with severe mental illness. It was hypothesised that a range of EE ratings would be found in staff, and that they would have high levels of burnout and stress. Job satisfaction was also measured. Ten staff were interviewed about 28 clients. Thirty nine percent of interviewees were rated as high EE (7/10 staff were high EE about at least one client), with low EE interviews showing significantly more warmth. Emotional exhaustion, depersonalisation and GHQ levels were above norms for the general population, and were similar to those found in other inner city community teams, but were not related to EE levels. Nevertheless personal accomplishment and job satisfaction were high. High EE interviews were related to increased client symptomatology. Implications for long term community care are discussed.

Adult↗
PubMed1996

DNA binding proteins from keloid fibroblasts form unique complexes with the human fibronectin promoter.

Keloids are pathological lesions characterized by enhanced expression of extracellular matrix molecules including fibronectin. A molecular dissection of the human fibronectin promoter was performed to identify DNA-protein interactions that correlate with altered fibronectin gene expression by keloid fibroblasts. DNA mobility shift patterns generated by nuclear extracts from skin, scar, and keloid fibroblasts were identical at a consensus CRE at -170 of the human fibronectin promoter whereas extracts from keloid fibroblasts formed complexes at a CRE/AP-1-like sequence at -415 that differed from those generated by skin and scar fibroblast extracts. The DNA-protein interactions identified at -415 were sensitive to altered serum concentrations in skin and scar but not keloid fibroblast cultures. The effects of forskolin and TGF-beta on fibronectin expression correlated with changes in the DNA-protein complexes assembled on the -170 and -415 cis elements, respectively. Oligonucleotides containing consensus CRE and AP-1 sequences did not compete for binding of nuclear proteins to the CRE/AP-1-like domain at -415, suggesting that this is a unique cis element. These studies indicate that the human fibronectin promoter contains two cis elements on which related but nonidentical complexes form. Alterations in the complexes interacting with the sequence at -415 may be responsible for the differences in fibronectin gene expression among quiescent skin, mature scar, and keloid fibroblasts.

Adolescent↗
PubMed1995

Transcriptional repression of fibronectin gene expression in v-src transformation.

V-src-dependent and -independent alterations in the steady-state content, rates of synthesis, and turnover of fibronectin protein and mRNA were identified using rat fibroblasts which are temperature sensitive for p60v-src activity. Activation of p60v-src caused a fivefold reduction in the rate of fibronectin biosynthesis. The v-src-dependent decrease in fibronectin biosynthesis resulted from a similar reduction in the steady-state content of fibronectin mRNA. This change was reversible and required more than 24 h, implying an indirect effect of p60v-src on fibronectin gene expression. The rate of fibronectin mRNA turnover and pattern of alternative splicing were unchanged following p60v-src activation, indicating that these regulatory steps are insensitive to v-src transformation. A v-src-specific reduction of at least threefold was measured for the rate of fibronectin gene transcription, and gene transfer studies using fibronectin promoter-CAT reporter genes indicated that transcriptional repression occurs at the level of initiation. When p60v-src was inactive, CAT reporter genes controlled by 4.9 or 3.2 kb of the rat fibronectin promoter exhibited relatively increased CAT activity (approximately twofold) compared to another CAT reporter construction controlled by only 880 bp of the fibronectin promoter. In contrast, CAT activity was relatively reduced (approximately twofold) for the reporter constructions containing 4.9 or 3.2 kb of the promoter when p60v-src was active. These findings indicate that the distal portion of the fibronectin promoter contains a v-src-sensitive element(s) which mediates a decrease in the rate of fibronectin transcription initiation by negative control.

Animals↗
PubMed1993

Technique integration. Therapeutic touch and theory-based mental health nursing.

Acceptance of therapeutic touch (TT) by the nursing community has become widespread. Nurses are advancing the pioneering work of Krieger (1973) through practice, research, education, and, most recently, through the development of theory-based nursing practice. The purpose of this article is to contribute to the development of theory-based nursing practice by introducing integration of TT with mental health nursing approaches. The Science of Unitary Human Beings (Rogers, 1986) is used to explain the relationship between TT and mental health nursing practice. The use of TT in practice is demonstrated through case examples from experiences with students and clients.

Female↗
PubMed1992

Uterine fibronectin mRNA content and localization are modulated during implantation.

Fibronectin mRNA and protein content were examined during embryonic implantation in the rat uterus. Content of total fibronectin mRNA at day 6 of pregnancy increased relative to the non-pregnant uterus. In contrast, fibronectin protein content of the subepithelial stroma was relatively decreased except in the region directly surrounding the lumen, and this fibronectin immunoreactivity was sensitive to hyaluronidase treatment. These changes are likely to reflect the degradation and subsequent remodeling of the previously stable uterine extracellular matrix in preparation for embryonic implantation. A+, B-, V + fibronectin mRNAs were present in both the non-pregnant and day 6 pregnant uterus with increased content of A+ and V+ fibronectin mRNAs in the latter. A + fibronectin mRNA was distributed throughout the endometrial stroma of the non-pregnant uterus and content of the subepithelial stroma increased by day 4 of pregnancy, coincident with progesterone action on the endometrium. On day 6 of pregnancy, fibronectin mRNAs encoding the V95 and A regions were preferentially localized to the mesometrial zone of the subepithelial stroma. Accumulation of these mRNA splicing variants at the mesometrial zone was dependent upon decidualization, but the embryo was not required. Thus, there are two major changes in uterine fibronectin gene expression as a result of pregnancy: increased fibronectin mRNA content and mesometrial localization. These changes suggest a key function for fibronectin in implantation and imply the operation of a regulatory program of fibronectin gene expression which depends on hormonal sensitization and a nidatory stimulus.

Animals↗
PubMed1992

Fibronectin gene transcription is enhanced in abnormal wound healing.

Abnormal wound healing in susceptible individuals can result in the formation of keloids that have an elevated content of extracellular matrix material compared to normal scars. Keloid-derived fibroblasts exhibit as much as a four-fold increase in the rate of fibronectin biosynthesis compared to fibroblasts from normal dermis and normal scars. Altered biosynthesis is due to an increase in the steady-state level of fibronectin mRNA, and in this investigation we have identified the level of fibronectin gene expression that is responsible for this increase. The rate of fibronectin gene transcription was found to be increased as much as threefold in keloid fibroblasts when compared to normal fibroblasts. Other possible changes that could account for the elevated level of fibronectin mRNA in keloids, such as increased copy number of the fibronectin gene or decreased turnover of fibronectin mRNA were also examined. The possibility of altered gene dosage was eliminated because chromosome content, G-banding patterns, and fibronectin gene content of keloid fibroblasts were all found to be normal. Analysis of fibronectin mRNA degradation revealed a half-life of approximately 13 h, and the residual fibronectin mRNA was observed to remain full length during this time period in both keloid and normal fibroblasts. Thus, altered degradation of fibronectin mRNA is unlikely to contribute to overproduction of fibronectin in keloids. Increased translational competence of fibronectin mRNA in keloids was also eliminated as a contributing factor because fibronectin mRNA remaining after one half-life were equally available for translation in both cell types. Although stimulation of transcription may not entirely account for the increase in fibronectin biosynthesis in keloids, this mechanism is best able to account for the majority of the change.

Adult↗