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Biomedical subjects

P Connell

Publications and source records attributed to P Connell.

14 recordsLinked to original sources
PubMed2004

Investigating ethnic differences in sexual health: focus groups with young people.

OBJECTIVES: To compare normative beliefs about sexual health in young men and women from black Caribbean, black African, and white ethnic groups in order to better understand ethnic inequalities in sexual health. METHODS: Focus group discussions with young people living in an area with known high prevalence of gonorrhoea and chlamydia. Groups were stratified by sex and self defined ethnicity. RESULTS: 22 male and 20 female 16-25 year olds of black Caribbean, black African, and white ethnicity took part in eight discussions. Participants from black ethnic groups were more aware of gonorrhoea than white participants but all ethnic groups regarded these as being less important than unplanned pregnancy or HIV/AIDS. Most participants believed that they would have obvious symptoms if they had a sexually transmitted infection and could determine the cleanliness of sexual partners by visual or behavioural cues. Black Caribbean women were alone in acknowledging the likelihood of their partners having concurrent sexual relationships. Some black Caribbean women described negative attitudes of staff in genitourinary medicine clinics who were from the same ethnic background. CONCLUSION: In this focus group study we identified ethnic differences in terminology, awareness of sexually transmitted infections, non-exclusive sexual relationships, and experience of sexual health services but gender had a greater influence on normative beliefs. The similarities in norms for all ethnic groups might reflect common social and cultural exposures. The low priority given to sexually transmitted infections by young people from all ethnic groups needs to be addressed if they are to be tackled successfully.

Adolescent↗
PubMed2003

'You can't tell by looking': pilot study of a community-based intervention to detect asymptomatic sexually transmitted infections.

Innovative and non-stigmatizing interventions are required to reduce ethnic inequalities in rates of sexually transmitted infections among young people. We therefore designed an intervention, 'You can't tell by looking,' which combined health promotion with testing for gonorrhoea and chlamydia using nucleic acid amplification technology and treatment and partner notification delivered in the non-clinical settings. One hundred and eighty-one participants were seen in 13 sessions in local further education colleges. Forty-three percent of participants were from Black Caribbean or Black Other ethnic groups and 39% were Black African: 125 of 181 participants were sexually active and 109 of these (87%) provided a urine specimen. 10/109 (9.2%, 95% confidence interval 4.5-16.2%) samples were confirmed positive for Chlamydia trachomatis and two were also positive for Neisseria gonorrhoeae. Only 7% of those tested found it embarrassing. The intervention was both feasible and acceptable to young people. It could be tested in a wider variety of non-clinical settings and evaluated in a cluster randomized trial.

Adolescent↗
PubMed2001

The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins.

To maintain quality control in cells, mechanisms distinguish among improperly folded peptides, mature and functional proteins, and proteins to be targeted for degradation. The molecular chaperones, including heat-shock protein Hsp90, have the ability to recognize misfolded proteins and assist in their conversion to a functional conformation. Disruption of Hsp90 heterocomplexes by the Hsp90 inhibitor geldanamycin leads to substrate degradation through the ubiquitin-proteasome pathway, implicating this system in protein triage decisions. We previously identified CHIP (carboxyl terminus of Hsc70-interacting protein) to be an interaction partner of Hsc70 (ref. 4). CHIP also interacts directly with a tetratricopeptide repeat acceptor site of Hsp90, incorporating into Hsp90 heterocomplexes and eliciting release of the regulatory cofactor p23. Here we show that CHIP abolishes the steroid-binding activity and transactivation potential of the glucocorticoid receptor, a well-characterized Hsp90 substrate, even though it has little effect on its synthesis. Instead, CHIP induces ubiquitylation of the glucocorticoid receptor and degradation through the proteasome. By remodelling Hsp90 heterocomplexes to favour substrate degradation, CHIP modulates protein triage decisions that regulate the balance between protein folding and degradation for chaperone substrates.

Animals↗
PubMed1999

Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.

The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.

Adenosine Triphosphatases↗
PubMed1997

Zinc attenuates tumor necrosis factor-mediated activation of transcription factors in endothelial cells.

OBJECTIVE: The objective of the study was to test the hypothesis that zinc can protect against endothelial dysfunction by interfering with oxidative stress-mediated cellular signaling and subsequent inhibition of an endothelial cell inflammatory response. Our approach was to compare alterations on molecular and biochemical levels with changes in endothelial barrier function that occur in zinc deficient conditions. METHODS: To investigate our hypothesis, endothelial cells were exposed to zinc deficient media for 2 to 10 days to deplete cellular zinc stores. Following this, half of the groups received zinc supplementation (9.2 microM) for 48 hours. The other half served as zinc deficient controls. These cells were then challenged with tumor necrosis factor-alpha (TNF) for varying time periods. Nuclear extracts were prepared from cells and analyzed for nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding. Media from cells were analyzed for interleukin 8 (IL-8) production, and cellular proteins were determined. RESULTS: Zinc supplementation resulted in a 74% increase in cellular zinc content. It was also shown that a 1.5 hour exposure to TNF (100 U/mL medium) significantly increased NF-kappa B and AP-1 binding, which was lowered considerably when cells were supplemented with physiological levels of zinc. Zinc supplementation also caused a marked attenuation in IL-8 expression by endothelial cells in response to TNF-mediated cell activation. DISCUSSION: Our previous data clearly show that zinc is a protective and critical nutrient for maintenance of endothelial integrity. The present data suggest that zinc may protect against cytokine-mediated activation of oxidative stress sensitive transcription factors, upregulation of inflammatory cytokines and endothelial cell dysfunction. This may have implications in understanding mechanisms of atherosclerosis.

Animals↗
PubMed1995

Differential sensitivity of p53(-) and p53(+) cells to caffeine-induced radiosensitization and override of G2 delay.

Most drug discovery efforts have focused on finding new DNA-damaging agents to kill tumor cells preferentially. An alternative approach is to find ways to increase tumor-specific killing by modifying tumor-specific responses to that damage. In this report, we ask whether cells lacking the G1-S arrest in response to X-rays are more sensitive to X-ray damage when treated with agents that override G2-M arrest. Mouse embryonic fibroblasts genetically matched to be (+) or (-) p53 and rat embryonic fibroblasts (+) or (-) for wild-type p53 function were irradiated with and without caffeine, a known checkpoint inhibitor. At low doses (500 microM), caffeine caused selective radiosensitization in the p53(-) cells. At this low dose (where no effect was seen in p53(+) cells), the p53(-) cells showed a 50% reduction in the size of the G2-M arrest. At higher doses (2 mM caffeine), where sensitization was seen in both p53(+) and p53(-) cells, the radiosensitization and the G2-M override were more pronounced in the p53(-) cells. The greater caffeine-induced radiosensitization in p53(-) cells suggests that p53, already shown to control the G1-S checkpoint, may also influence aspects of G2-M arrest. These data indicate an opportunity for therapeutic gain by combining DNA-damaging agents with compounds that disrupt G2-M arrest in tumors lacking functional p53.

Animals↗
PubMed1995

Ovulation rate and the concentrations of gonadotrophic and metabolic hormones in ewes fed lupin grain.

An experiment in which a lupin grain supplement was fed to ewes (n = 11) over days 2-13 of the oestrous cycle was carried out. A group of 12 ewes was used as a control and not fed the supplement. Plasma concentrations of LH and GH (20 min intervals) and FSH, insulin and prolactin (hourly intervals) were determined in plasma samples collected every 20 min over 24 h on day 11 of the oestrous cycle. The changes were related to increases in ovulation rate. Ovulation rate was increased (2.5 +/- 0.2 versus 1.9 +/- 0.2 for lupin-supplemented and control groups, respectively; P = 0.073) in the group that received the lupin supplement, but this increase was not associated with significant changes in either LH or FSH concentrations on day 11 of the oestrous cycle. Lupin supplementation had significant effects on the plasma concentrations of prolactin, GH and insulin. There was a transient increase (P < 0.05) in the concentration of prolactin 4-8 h after feeding, whereas insulin concentrations were increased immediately after feeding (P < 0.02) and were still high 24 h later (P < 0.02). Growth hormone concentrations were reduced in ewes fed with lupin grain (P < 0.001). These metabolic responses initiated by feeding a high energy and protein supplement such as lupin grain may be related to changes in ovulation rate. In particular, the sustained increases in insulin concentrations suggest that an increased supply of glucose to the follicle mediates nutritionally stimulated increases in ovulation rate.

Amino Acids↗
PubMed1984

The clinical effectiveness of electrostimulation vs oral methadone in managing opiate withdrawal.

A group of 24 opiate addicts admitted to an in-patient drug dependence unit received either electrostimulation or graduated oral methadone withdrawal. Addicts treated with electrostimulation showed high levels of withdrawal symptoms during the first week of treatment: these reached a peak on Day 3. In this respect electrostimulation was markedly inferior to methadone withdrawal treatment. However, although progressive methadone withdrawal quickly reduced symptoms to a moderate or low level, there was no reduction in symptomatology as late as one month after admission (i.e. after ten days without methadone). The implications of these findings are discussed.

Adult↗
PubMed1983

Drug dependence, who gets treated?

Despite the fact that decisions about whether or not to admit patients to inpatient facilities are often made on the basis of "clinical judgment," there is little evidence to support the validity of this process. The present study investigates the ability of the staff at a London drug clinic to predict how addicts would behave after admission to an inpatient treatment unit, and the bases upon which decisions were reached. The results indicate that predictions on almost all measures of future behavior showed very little interrater reliability, and there was no way of knowing in advance who would do well and who would do badly. The predictions were not random guesses; they reflected "implicit theories" held by each rater about the sort of factors that they believed to operate in such circumstances. Some implications of these findings for the treatment of addicts are discussed.

Humans↗
PubMedDate not supplied

The relationship of blood pressure to cardiac hypertrophy: experimental studies in rats.

Cardiac hypertrophy is an independent predictor of morbidity and mortality. The exact relationship between blood pressure, hormones and cardiac hypertrophy is unclear. This study was undertaken to determine if intermittent elevation of blood pressure could cause left ventricular hypertrophy. Blood pressure was elevated intermittently by intraperitoneal injections of angiotensin II, noradrenalin and methoxamine. Blood pressure was acutely elevated by 60 mmHg or more for periods lasting up to 1 hour on up to 4 occasions each day. Cardiac index was measured 2 and 4 weeks after the experiment started. The cardiac index was increased by all procedures. The results were complicated by a retardation of growth in some experimental groups, meaning that the cardiac weight did not increase though the index did. In a study looking at the interaction of sodium and angiotensin II high sodium intake caused left ventricular hypertrophy and injections of angiotensin II caused further left ventricular hypertrophy. This study indicated that acute intermittent elevation of blood pressure could cause left ventricular hypertrophy and suggests that wall stress rather than 24 hour workload is the important triggering mechanism.

Angiotensin II↗