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C Neil

Publications and source records attributed to C Neil.

10 recordsLinked to original sources
PubMed2000

Multiple copies of beta-lactoglobulin promoter do not function as LCR.

Increasing the number of transcription factor binding sites within a construct can enhance expression. In an attempt to create a synthetic locus control region for mammary expression, we have generated beta-lactoglobulin-reporter constructs with multiple copies of the cluster of transcription sites normally located within the proximal promoter. These constructs were functionally tested by stable transfection of mammary epithelial cells in vitro and in transgenic mice in vivo. Rather than enhancing expression, multimerisation of the promoter region acted neither in vivo nor in vitro to enhance expression. Indeed, its presence reduced expression. This failure to enhance expression was reflected in the inability of this region to form a DNaseI hypersensitive site autonomously in mammary chromatin in vivo. It is implicit from our study that not all combinations of transcription factor binding sites will enhance transcription.

Animals↗
PubMed2000

Deletion of the gene encoding H-FABP/MDGI has no overt effects in the mammary gland.

Heart fatty acid binding protein (H-FABP) is expressed abundantly in the mammary gland. A number of in vitro studies have shown that H-FABP is functionally indistinguishable from a factor isolated from this organ, termed mammary derived growth inhibitor (MDGI), which specifically inhibits the proliferation of mammary tissue. We have previously shown that over-expression of H-FABP/MDGI in the mammary gland of transgenic mice has no discernable effects on cell proliferation or differentiation. In this report we describe knockout mouse in which the H-FABP/MDGI gene has been specifically disrupted. The mice exhibit no overt phenotype in the mammary gland, and we conclude that this gene does not play a specific role in regulating the normal development or function of this tissue.

Animals↗
PubMed1997

Selective cell ablation in transgenic mice expression E. coli nitroreductase.

The gene encoding E. coli nitroreductase (NTR) was expressed in the luminal cells of the mammary gland of transgenic mice using the ovine beta-lactoglobulin promoter. Treatment of NTR expressing animals with the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) resulted in a rapid and selective killing of this population of cells whereas the closely associated myoepithelial cells were unaffected. NTR-mediated inducible cell ablation offers a number of advantages over the use of HSV1-tk for the selective killing of cells in vivo.

Animals↗
PubMed1992

Antiinflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Comparative studies with indomethacin.

6MNA, the active metabolite of the nonacidic antiinflammatory drug nabumetone, was investigated using intravenous administration for effects on (1) carrageenan paw edema and gastric irritancy compared with either oral nabumetone or both oral and intravenous indomethacin when given acutely and (2) gastrointestinal irritancy when given in repeat dosing studies. Oral doses of nabumetone or intravenous 6MNA produced effective antiinflammatory activity together with significant inhibition of paw exudate PGE2. Antiinflammatory oral doses of nabumetone or intravenous 6MNA produced minimal effects on gastric 6-keto PGF1 alpha production with an absence of gastric damage, in contrast with indomethacin. In repeat dose studies, 6MNA failed to induce gastrointestinal damage even at doses where general toxicity was evident. These results show that in the rat, 6MNA is an effective antiinflammatory drug but even in very high intravenous doses does not have the propensity to induce gastrointestinal damage.

Administration, Oral↗
PubMed1992

Anti-inflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6MNA (6-methoxy-2-naphthylacetic acid): comparison with indomethacin.

6MNA, the active metabolite of the non-acidic anti-inflammatory drug nabumetone, was investigated using intravenous administration for effects on (a) carrageenan paw oedema and gastric irritancy compared to either oral nabumetone or both oral and intravenous indomethacin when given acutely and (b) gastrointestinal irritancy when given in repeat dosing studies. An oral dose of nabumetone or intravenous 6MNA produced effective anti-inflammatory activity together with significant inhibition of paw exudate PGE2. An anti-inflammatory oral dose of nabumetone or intravenous 6MNA produced minimal effects on gastric 6-keto-PGF1 alpha production, with an absence of gastric damage, in contrast to indomethacin. In repeat dose studies, 6MNA failed to induce gastrointestinal damage even at doses where general toxicity was evident. These results show that in the rat 6MNA, the active metabolite of nabumetone, is an effective anti-inflammatory drug but, even in very high intravenous doses, does not have the propensity to induce gastrointestinal damage.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Predictors of bereavement outcome for family carers of cancer patients.

AIMS: The psychological outcome of family carers after bereavement is an important issue in evaluating palliative care services. Palliative care services have the potential to provide preventive psychosocial intervention to family carers prior to bereavement, but are faced with the need to identify those who may have greatest risk of adverse outcome. This prospective study examines predictors of psychological outcome for family carers of cancer patients following bereavement based on factors identified at referral to a palliative care agency. METHODS: Cancer patients and their family carer were consecutively recruited and assessed on a range of clinical and psychological measures at referral to a palliative home care service in a metropolitan centre (Time 1). Carers were again assessed following the death of the patient, on average at 4 months post-bereavement (Time 2), using measures of bereavement symptoms and psychological morbidity. RESULTS: 178 carers were assessed on both occasions. The chief predictors of carer psychological symptoms and severity of grief at follow-up were psychological symptom scores at the time of referral (Time 1). Factors also measured at Time 1 were significant predictors of symptoms and grief scores at Time 2: greater number of adverse life events, carer's coping responses, past bereavement and separation experiences, the relationship with the patient, and greater severity of patient's illness at the time of palliative care referral. CONCLUSIONS: The findings indicate clinical risk factors for adverse short-term bereavement outcome that can be identified in family carers during palliative care treatment, that have implications for identifying the psychological needs of carers, and that form a potential basis for interventions to enhance the psychological outcome for family carers.

Adaptation, Psychological↗