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Biomedical subjects

S Hooper

Publications and source records attributed to S Hooper.

15 recordsLinked to original sources
PubMed1999

Activated MEK stimulates expression of AP-1 components independently of phosphatidylinositol 3-kinase (PI3-kinase) but requires a PI3-kinase signal To stimulate DNA synthesis.

To investigate the contribution that ERK/mitogen-activated protein kinase signalling makes to cell cycle progression and gene expression, we have constructed cell lines to express an inducible version of activated MEK1. Using these cells, we show that activation of MEK leads to the expression of Fra-1 and Fra-2 but not c-Fos. Treatment of Ras-transformed cells with the MEK inhibitor PD098059 blocks expression of Fra-1 and Fra-2, showing that in Ras transformation ERK signalling is responsible for Fra-1 and Fra-2 expression. Activation of MEK1 in growth-arrested cells leads to DNA synthesis; however, ERK activation alone is insufficient because the induction of DNA synthesis is blocked by inhibition of phosphatidylinositol 3-kinase (PI3-kinase). Activation of PI3-kinase is indirect, perhaps through autocrine growth factors, and is required for the induction of cyclin D1.

3T3 Cells↗
PubMed1998

Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2.

BACKGROUND: Mitogen-activated protein (MAP) kinases (or extracellular signal regulated kinases; Erks) and stress-activated protein (SAP) kinases mediate cellular responses to a wide variety of signals. In the Erk MAP kinase pathway, activation of MAP kinases takes place in the cytoplasm and the activated enzyme moves to the nucleus. This translocation to the nucleus is essential to MAP kinase signalling because it enables the kinase to phosphorylate transcription factors. Whether components of the pathway mediated by the SAP kinase p38 change their cellular location on activation is not clear; we have therefore studied the cellular localisation of components of this pathway before and after stimulation. RESULTS: The p38 SAP kinase substrate MAP-kinase-activated protein kinase-2 (MAPKAP kinase-2) contains a putative nuclear localisation signal which we show is functional and required for activation by a variety of stimuli. Following phosphorylation of MAPKAP kinase-2, nuclear p38 was exported to the cytoplasm in a complex with MAPKAP kinase-2. Export of MAPKAP kinase-2 required phosphorylation by p38 but did not appear to require the kinase activity of MAPKAP kinase-2. The p38 activators MKK3 and MKK6 were present in both the nucleus and the cytoplasm, consistent with a role in activating p38 in the nucleus. CONCLUSIONS: In the p38 SAP kinase pathway, MAPKAP kinase-2 serves both as an effector of p38 by phosphorylating substrates and as a determinant of cellular localisation of p38. Nuclear export of p38 and MAPKAP kinase-2 may permit them to phosphorylate substrates in the cytoplasm.

Amino Acid Sequence↗
PubMed1998

Aortic transection.

BACKGROUND: Traumatic aortic transection is uncommon in those trauma patients reaching hospital alive. METHODS: The Victorian Major Trauma Study (VMTS) received data from 25 hospitals in Victoria, a State of 4.4 million people, and identified 1874 patients with blunt trauma and Injury Severity Score (ISS) greater than 15 over a 2-year period (1 March 1992-28 February 1993 and 1 May 1994-30 April 1995). The Federal Office of Road Safety (FORS) examined coronial data from 1 January 1992 to 31 December 1992. These studies allowed a retrospective, population-based review of experience with aortic transection. RESULTS: The VMTS identified 19 patients who reached hospital, with signs of life at the scene of the accident, during a 2-year period. Of these, 8 left hospital alive: 4 without disability and 4 with disability related to non-thoracic injury. The annual incidence of aortic transection for the State, based on FORS data, was 13 per 1000000, lower than other reported studies. Review of the management of patients in hospital confirmed the usefulness of initial chest X-ray in diagnosis and the high incidence of associated injury. CONCLUSIONS: The study raises a number of issues, including the question of direct referral of patients with severe chest injury to hospitals with cardiothoracic facilities, increased use of transoesophageal echocardiography in diagnosis and increased use of immediate laparotomy and thoracotomy in certain patients.

Adult↗
PubMed1996

Rib fractures in major trauma.

BACKGROUND: To determine the mortality, hospital and intensive care unit (ICU) stay of rib fractures in patients admitted to Victorian hospitals for more than 1 day. METHODS: All patients fitting the entry criteria for the Victorian Major Trauma Study with fractured ribs were identified between 1 March 1992 and 28 February 1993. Aetiology, age, sex, associated injury and outcome were analysed. RESULTS: Patients with rib fractures had a higher mortality and length of hospital stay, but this was not significantly different from other trauma. A significantly higher percentage of patients required ICU care for rib fractures (44%) compared with the total group with blunt injury (24%). The majority of rib fractures resulted from motor vehicle accidents 361/541 (67%). Injuries occurring on the street/highway resulting in rib fractures were more likely to be major; 62% had Injury Severity Score (ISS) > 15. Fractured ribs occurred more commonly with increased age. Mortality for patients with fractured ribs versus total trauma group was higher in elderly patients. Univariate analysis showed rib fractures were a positive predictor of death but when adjusted for ISS and age, rib fractures became a negative predictor. Rib fractures were not predictors for length of ICU or hospital stay. CONCLUSION: The sample of rib fractures collected in this study underestimates the overall incidence. For those patients admitted to hospital with identified rib fractures, there is a trend towards higher mortality and morbidity. However, this association is better predicted by ISS and age.

Adolescent↗
PubMed1995

Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.

Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid that activates cells involved in inflammation. The biological activity of PAF depends on its structural features, namely an ether linkage at the sn-1 position and an acetate group at the sn-2 position. The actions of PAF are abolished by hydrolysis of the acetyl residue, a reaction catalysed by PAF acetylhydrolase. There are at least two forms of this enzyme--one intracellular and another that circulates in plasma and is likely to regulate inflammation. Here we report the molecular cloning and characterization of the human plasma PAF acetylhydrolase. The unique sequence contains a Gly-Xaa-Ser-Xaa-Gly motif commonly found in lipases. Recombinant PAF acetylhydrolase has the substrate specificity and lipoprotein association of the native enzyme, and blocks inflammation in vivo: it markedly decreases vascular leakage in pleurisy and paw oedema, suggesting that PAF acetylhydrolase might be a useful therapy for severe acute inflammation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Otitis media, hearing sensitivity, and maternal responsiveness in relation to language during infancy.

The relation of otitis media with effusion (OME) and associated hearing loss to language and cognitive skills at 1 year of age was studied to determine whether OME-related hearing loss had a direct association with language and cognitive outcomes at 1 year of age or an indirect association with these outcomes, as mediated by the child-rearing environment. Subjects were 61 black infants attending community-based child care programs. The presence of OME was assessed biweekly from 6 to 12 months of age by otoscopy and tympanometry. Hearing was assessed with visual reinforcement audiometry when children were well and when ill with OME. Language and cognitive skills and the child-rearing environment at home and in child care were examined. The results indicated a modest correlation between hearing loss associated with OME and receptive language. However, the direct association between OME-related hearing loss and all the language and cognitive measures was negligible. Hearing loss had an indirect association with receptive and expressive language, cognitive development, and overall communication as mediated by child-rearing factors. That is, children with more frequent hearing loss tended to have less responsive mothers and home environments, and this association was linked to lower performance on the infant assessments.

Adult↗
PubMed1995

Major trauma in Australia: a regional analysis.

This study was undertaken to evaluate the frequency, distribution, cause, pattern, and outcome of patients suffering from major trauma in the State of Victoria over a 1-year period. No previous study in Australia has attempted a comprehensive regional analysis of major trauma. All major trauma admissions resulting from blunt, penetrating, and burns injury were identified, and data collected from emergency departments and intensive care log books at 25 major metropolitan and rural hospitals from the January 3, 1992 to February 28, 1993 by onsite data collectors. The total number of patients admitted into the study was 2,944. There were 1,076 major trauma cases with an Injury Severity Score greater than 15 in a population of 4.2 million people. The type of injury was predominantly blunt (87.5%), with only a small percentage of penetrating injuries (6.4%) and burns (6%). Major trauma in pediatric cases is less common (132 cases). The most common causes of injury were road transport (56%) and falls (22%). The overall outcome of the group was favorable when compared with the Major Trauma Outcome Study group (Z = 1.4, M = 0.93, W = 0.52). There was an unexpectedly low number of patients suffering from major trauma. Outcome using Trauma and Injury Severity Score methodology was favorable when compared with North America.

Adolescent↗
PubMed1995

Patterns of injury from major trauma in Victoria.

Basic demographic and injury data were collected on all major trauma patients (ISS > 15) presenting to 25 Victorian hospitals over a 1 year period (March 1992-February 1993). A total of 1076 patients were identified with an Injury Severity Score (ISS) > 15. Of these, 957 resulted from blunt trauma, 68 from penetrating trauma and 51 from burns. Most serious blunt injury was transport-related (n = 652) but falls made up a significant proportion (n = 206). The pattern of injury in blunt trauma demonstrated in this study showed a preponderance of serious head, thoracic and limb injuries with less frequent occurrences of abdominal, spine and facial injuries. In major penetrating trauma, serious injuries of the thorax and abdomen were more frequent. Head injury is the most common cause of morbidity in major trauma patients. Motor vehicle accidents caused the majority of head injuries but, proportionately, head injury was more common in pedal cycle, pedestrian, motorcycle injuries and falls. The low frequency of major abdominal trauma has important implications for surgical training and resource allocation. In Victoria, various injury prevention interventions have been introduced such as compulsory wearing of bicycle helmets, a safer home environment and behavioral modifications through advertising. Injury prevention strategies must continue to target the populations at risk and assess the impact of interventions by accurate injury surveillance.

Accidents, Home↗
PubMed1995

Biomechanical responses of elite swimmers to staleness and recovery.

Tethered swimming forces (TSF), average distance achieved per stroke (D/S) during a submaximal effort swim, and time and D/S for a maximal effort swim were measured to determine changes occurring with staleness and recovery. Fourteen nationally ranked male and female swimmers were studied five times (i.e. early-, mid-, and late-season, during tapering, and after competition). ANOVA and Newman-Keuls post-hoc tests were used to assess changes during the season. Three swimmers were classified as stale and showed a deterioration (0.7%) in maximal performance time from early- to late-season which was significantly different (P < 0.05) from the improvement (3.1%) demonstrated by the non-stale swimmers. Daily self-ratings of fatigue, kept by the swimmers in log books during the season, were significantly higher (P < 0.001) for the stale compared with the non-stale swimmers. No significant differences were established between the stale and non-stale swimmers in TSF or D/S during the season or in the response to tapering. A significant improvement (P < 0.05) in TSF was observed from before to after tapering. It was concluded that TSF and D/S may not change significantly with staleness and that the recovery period of tapering prior to competition allows swimmers to generate greater forces in the water.

Adaptation, Physiological↗
PubMed1994

Mucosal (secretory) immune system responses to exercise of varying intensity and during overtraining.

Athletes are susceptible to upper respiratory tract infection (URTI) during intense training and after major competition; high rates of URTI have also been associated with the overtraining syndrome (staleness). Secretory immunoglobulin A (IgA), the predominant immunoglobulin in mucosal secretion, is a major effector of resistance against pathogenic microorganisms causing URTI. Previous work has shown that salivary IgA levels decrease after a single bout of intense prolonged exercise. The purpose of these studies was to examine the IgA response to various exercise conditions. Whole, unstimulated saliva was obtained before and after exercise. IgA concentration (microgram.mg protein-1) was measured by ELISA and IgA secretion rate (microgram.min-1) calculated. Study 1: Recreational joggers ran on a treadmill for 40 min at 55% and 75% VO2peak and competitive distance runners ran for 90 min at the same intensites. In both groups, IgA secretion rate did not change significantly after exercise at either intensity. Study 2: Competitive runners ran on a treadmill for 90 min at 75% VO2peak on 3 consecutive days. IgA secretion rate decreased 20 to 50% after exercise (p < .001). Post-exercise IgA secretion rates were significantly lower (p < .05) on days 2 and 3 compared with day 1. Study 3: Elite swimmers were followed over a 6 month season, with IgA concentration measured at 5 times. Throughout the season, IgA concentration was significantly (p < .05) lower in stale compared with well-trained swimmers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of restricting uteroplacental blood flow on concentrations of corticotrophin-releasing hormone, adrenocorticotrophin, cortisol, and prostaglandin E2 in the sheep fetus during late pregnancy.

We have examined the effects of reduced uterine blood flow and prolonged fetal hypoxemia on the temporal relationship between changes in hormones associated with the activity of the pituitary-adrenal axis (corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), cortisol, and prostaglandin E2 (PGE2) in the ovine fetus at 120-125 days of pregnancy, and we sought evidence for placental secretion of CRH and ACTH during prolonged hypoxemia. Uterine blood flow was reduced by placing an adjustable Teflon clamp around the maternal common internal iliac artery to decrease fetal arterial oxygen saturation from mean values of 59.1 +/- 3.3 to 25.7 +/- 4.6% (+/- SEM, n = 10). There was a transient peak in immunoreactive (IR-) CRH at 1-2 h after reducing uterine blood flow. IR-ACTH rose to peak values at +2 h, then gradually decreased to control level by +12 h. Fetal plasma cortisol and PGE2 concentrations were elevated significantly by +2 and +4 h, respectively, and at 20-24 h. The identity of IR-CRH in fetal plasma and in ovine placental extracts was confirmed by HPLC, but there was no consistent umbilical vein--femoral arterial concentration difference for either IR-CRH or IR-ACTH during normoxemia or hypoxemia. We conclude that a sequence of endocrine changes involving CRH, ACTH, PGE2, and cortisol occurs in the fetus during a prolonged reduction in uterine blood flow. However, we did not obtain evidence, for placental secretion of either CRH or ACTH in response to this manipulation.

Adrenocorticotropic Hormone↗
PubMed1986

Stability of teacher temperament ratings over 6 and 12 months.

Six and 12-month stability of teacher ratings of temperament was studied in four samples. For the two samples retested after a 6-month interval, the same teacher provided the original and retest ratings. For the two samples retested after a 12-month interval, different teachers provided the retest ratings than provided the original ratings. Four indices of stability were investigated for each sample: cross-rank stability, within-person stability , absolute score stability, and factorial stability. Factorial stability was demonstrated for all samples. For the other three indices of stability, 6-month stability was moderate to high, and significantly higher than the 12-month stability. The general pattern of results is comparable to temperament rating data from parents, with specific coefficients being somewhat higher.

Child↗
PubMed1982

Assessment of the metabolic effects of dietary carbohydrate and fibre by measuring urinary excretion of C-peptide.

An assessment of the metabolic effect of dietary carbohydrate on daily insulin secretion, reflected by the 24-h urine output of C-peptide, has been made. Urinary C-peptide excretion increased when the carbohydrate intake of 6 normal subjects was increased from 200 to 400 g. A high-fibre diet rich in beans and lentils caused a significant fall in urine C-peptide and a lowering of blood glucose values in both normal and diabetic subjects. This confirms the insulin-sparing effect of leguminous foods. An increase of dietary fibre to 50 g mainly as cereal fibre did not significantly alter urine C-peptide excretion in normal subjects. Urinary C-peptide estimations could be useful for assessing the effect of different diets on daily insulin secretion.

Adult↗