Search PubMed⌕ Search

Biomedical subjects

S Henderson

Publications and source records attributed to S Henderson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Jun NH2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress.

The p53 tumor suppressor protein plays a key role in the regulation of stress-mediated growth arrest and apoptosis. Stress-induced phosphorylation of p53 tightly regulates its stability and transcriptional activities. Mass spectrometry analysis of p53 phosphorylated in 293T cells by active Jun NH2-terminal kinase (JNK) identified T81 as the JNK phosphorylation site. JNK phosphorylated p53 at T81 in response to DNA damage and stress-inducing agents, as determined by phospho-specific antibodies to T81. Unlike wild-type p53, in response to JNK stimuli p53 mutated on T81 (T81A) did not exhibit increased expression or concomitant activation of transcriptional activity, growth inhibition, and apoptosis. Forced expression of MKP5, a JNK phosphatase, in JNK kinase-expressing cells decreased T81 phosphorylation while reducing p53 transcriptional activity and p53-mediated apoptosis. Similarly transfection of antisense JNK 1 and -2 decreased T81 phosphorylation in response to UV irradiation. More than 180 human tumors have been reported to contain p53 with mutations within the region that encompasses T81 and the JNK binding site (amino acids 81 to 116). Our studies identify an additional mechanism for the regulation of p53 stability and functional activities in response to stress.

Animals↗
PubMed2001

Perfusion mapping using computed tomography allows accurate prediction of cerebral infarction in experimental brain ischemia.

BACKGROUND AND PURPOSE: We have developed a dynamic CT method to measure absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). In this study we evaluated the ability of CT-derived functional maps to detect infarction in a rabbit model of focal cerebral ischemia. METHODS: Sequential dynamic CT studies were performed at 2 different slices in 5 control rabbits and another 8 after induction of focal cerebral ischemia. The size of critically ischemic tissue was correlated to size of infarction measured by postmortem 2,3,5-triphenyltetrazolium chloride staining. In the control rabbits, short-term variability of the parameters was assessed by ANOVA analysis. RESULTS: In 7 of 8 animals of the ischemia group, cerebral infarction was visible on 2,3, 5-triphenyltetrazolium chloride staining, constituting 16.7+/-10.6% of the ipsilateral hemisphere. Good agreement of CBF functional maps with tissue specimens was found with respect to size and location of infarction. Best prediction of infarction was found for thresholds of CBF <10 mL/100 g per minute (mean size, 17.5+/-13.4%; r=0.95) and MTT >6 seconds (mean size, 15.6+/-13.5%; r=0.85), with regression slopes close to unity. CBV maps were less predictive of occurrence of infarction, especially in cases of small infarction. The short-term variability of CBF, CBV, and MTT in the control group was 10.9%, 15.2%, and 19.9%, respectively. CONCLUSIONS: Functional CT measurements of absolute CBF and MTT early after onset of ischemia allow prediction of the size and location of cerebral infarction with good accuracy.

Animals↗
PubMed2001

Prevalence, comorbidity, disability and service utilisation. Overview of the Australian National Mental Health Survey.

BACKGROUND: Health planning should be based on data about prevalence, disability and services used. AIMS: To determine the prevalence of ICD-10 disorders and associated comorbidity, disability and service utilisation. METHOD: We surveyed a national probability sample of Australian households using the Composite International Diagnostic Interview and other measures. RESULTS: The sample size was 10 641 adults, response rate 78%. Close to 23% reported at least one disorder in the past 12 months and 14% a current disorder. Comorbidity was associated with disability and service use. Only 35% of people with a mental disorder in the 12 months prior to the survey had consulted for a mental problem during that year, and most had seen a general practitioner. Only half of those who were disabled or had multiple comorbidity had consulted and of those who had not, more than half said they did not need treatment. CONCLUSIONS: The high rate of not consulting among those with disability and comorbidity is an important public health problem. As Australia has a universal health insurance scheme, the barriers to effective care must be patient knowledge and physician competence.

Adolescent↗
PubMed2001

Gabapentin in the treatment of cocaine dependence: a case series.

BACKGROUND: Although multiple medications have been studied for the treatment of cocaine dependence, no medication has been shown to have a robust effect on craving and use. This pilot project was designed to evaluate the safety and tolerability of gabapentin in subjects with cocaine dependence. METHOD: Thirty cocaine-dependent subjects (DSM-IV criteria) were enrolled in an 8-week, open-label trial of 1,200 mg/day of gabapentin in divided doses. Urine drug screens, subjective measures of craving, and cocaine use interviews were conducted at each weekly visit. RESULTS: Baseline rating of amount and frequency of craving decreased significantly by week 8 (78% vs. 25% for amount, p = .000; 74% vs. 23% for frequency, p = .004). Positive urine drug screens for cocaine decreased from 86% at baseline to 29% at weeks 4 and 8. There were no reports of significant side effects or adverse events. CONCLUSION: This pilot study indicates that gabapentin is safe and well tolerated and may be beneficial in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.

Acetates↗
PubMed2001

Aerodigestive injuries of the neck.

Cervical aerodigestive trauma is rare and most centers have a limited experience with its management. The purpose of this review was to study the epidemiology, diagnosis, and problems related to the early evaluation and management of these injuries. This was a retrospective study based on trauma registry and on chart, operative, radiological, and endoscopic reports. There were 1560 admissions with blunt or penetrating trauma to the neck. The overall incidence of aerodigestive trauma was 4.9 per cent (10.2% for gunshot wounds, 4.6% for stab wounds, and 1.2% for blunt trauma). All patients with aerodigestive trauma had suspicious signs or symptoms on admission. The most common life-threatening problem in the emergency room and directly related to the aerodigestive trauma was airway compromise. Twenty-nine per cent of patients with laryngotracheal trauma required an emergency room airway establishment because of threatened airway loss. Although rapid sequence induction was successful in the majority of cases, in 11.9 per cent there was loss of airway and a cricothyroidotomy was necessary. Overall, 9 per cent of cases with aerodigestive injuries were successfully treated nonoperatively. Thirty-six per cent of patients with laryngotracheal trauma and surgical repair were successfully treated without a protective tracheostomy. There was no mortality due to the aerodigestive injuries. Cervical aerodigestive trauma is rare. In conclusion, all patients with significant aerodigestive injuries requiring treatment had suspicious signs and symptoms. Airway compromise was a common problem in the emergency room. Loss of airway after rapid sequence induction is a potentially lethal complication and the trauma team should be ready for a surgical airway. Repair of laryngotracheal injuries without a protective tracheostomy is safe in selected cases.

Airway Obstruction↗
PubMed2001

Utility of a new assay for carbohydrate-deficient transferrin (Biorad %CDT TIA) to monitor abstinence during a treatment outcome study.

BACKGROUND: The ability to reliably detect heavy alcohol use is important in both clinical and research populations. The current study evaluates the utility of the newest method of measuring carbohydrate deficient transferrin (CDT) in monitoring the abstinence during a treatment outcome study. METHODS: Blood from 40 alcohol dependent individuals was obtained at baseline and at weeks 4, 8, and 12 of treatment. Differences in percent of baseline GGT and %CDT levels were analyzed in people who remained abstinent throughout treatment (abstainers) and in those who consumed alcohol during treatment (drinkers). RESULTS: There was a significant decrease in the percent of baseline %CDT levels in the subjects who abstained at week 4 and a trend at weeks 8 and 12. Conversely, there were no significant differences in percent of baseline GGT levels between drinkers and abstainers at any time point. CONCLUSIONS: Although small in nature, this study provides preliminary evidence for the use of the relatively new Biorad %CDT assay to monitor drinking status during treatment outcome studies. This study is also consistent with previously reported findings that GGT appears to be less sensitive than %CDT in detecting the consumption of alcohol. A larger trial focusing on sex differences in the utility of % CDT to monitor outcome would be of interest.

Adult↗
PubMed2000

Regulation of mOAT-mediated organic anion transport by okadaic acid and protein kinase C in LLC-PK(1) cells.

Organic anion transporters in the kidney proximal tubule play an essential role in eliminating a wide range of organic anions including endogenous compounds, xenobiotics, and their metabolites, thereby preventing their potentially toxic effects within the body. We have previously cloned a cDNA encoding an organic anion transporter from mouse kidney (mOAT) (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J. G., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478; Kuze, K., Graves, P., Leahy, A., Wilson, P., Stuhlmann, H., and You, G. (1999) J. Biol. Chem. 274, 1519-1524). In the present study, we assessed the potential for regulation of this transporter by heterologous expression of mOAT in the pig proximal tubule-like cell line, LLC-PK(1). We report here that both protein phosphatase (PP1/PP2A) inhibitor, okadaic acid, and protein kinase C (PKC) activators down-regulate mOAT-mediated transport of para-aminohippuric acid (PAH), a prototypic organic anion, in a time- and concentrationdependent manner. However their mechanisms of action for this down-regulation are distinct. Okadaic acid modulated PAH transport, at least in part, through phosphorylation/dephosphorylation of mOAT; phosphoamino acid analysis indicated this phosphorylation occurs on serine. In contrast, PKC activation induced a decrease in the maximum transport velocity (V(max)) of PAH transport without direct phosphorylation of the transporter protein. Together these results provide the first demonstration that regulation of organic anion transport by mOAT is likely to be tightly controlled directly and indirectly by phosphatase PP1/PP2A and PKC. Our results also suggest that kinases other than PKC are involved in this process.

Animals↗
PubMed2000

Methanol poisoning.

AIMS: This study examines clinical experience with methanol poisoning during a one-year period. METHODS: All admissions with the diagnosis of suspected methanol toxicity were analysed and the current guidelines for the management of this problem were reviewed. RESULTS: Twenty-four subjects were identified. Most had a history of chronic use of methylated spirits. Four died before admission to hospital and the other 20 patients had 26 admissions to hospital and form the basis for this report. Four patients died in the Intensive Care Unit. In total 11 patients were admitted to the Intensive Care Unit. Seven patients received haemodialysis. There was no correlation between the methanol level and the outcome. The strongest predictor of death or a poor outcome was a blood pH < 7.0. Some patients, in spite of potentially lethal methanol levels of up to 160 mmol/L, did not develop signs of toxicity. CONCLUSIONS: The overall mortality was high and ethanol was given to most of the patients for up to several days. Some patients did not show any toxicity and some of those were not given ethanol. It is recommended that chronic meths drinkers, who are not acidaemic and are generally well, do not require ethanol treatment. Only the complete removal of methanol from methylated spirits will reduce the morbidity of this condition.

Adult↗
PubMed2000

Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors.

More than 40 mutants in Caenorhabditis elegans have been demonstrated to lead to increased life span (a rigorous, operational test for being a gerontogene) of 20% or more ("Age" mutants). Age mutants alter rate-limiting determinants of longevity; moreover, important genes are identified independent of prior hypotheses as to actual mode of gene action in extending longevity and/or "slowing" aging. Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Three well-studied mutants (age-1, clk-1, and spe-26) alter age-specific mortality rates in characteristic fashions; in age-1 mutants, especially, the changes in mortality rates are quite dramatic. All Age mutants (so far without exception) increase response to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies, as well as random mutagenesis, to identify novel genes increasing the worm's ability to resist stress. Two genes (daf-16 and old-1) yield over-expression strains that are stress resistant and long-lived. A variety of approaches to assess transcriptional alterations associated with increased longevity are underway. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress.

Aging↗
PubMed2000

Risk factors for depression and anxiety in abstainers, moderate drinkers and heavy drinkers.

AIMS: To identify risk factors for depression and anxiety that are more prevalent in abstainers than in moderate drinkers and to estimate their contribution to U-shaped relationships of depression and anxiety with alcohol consumption. DESIGN: Cross-sectional general population sample. SETTING: Canberra, Australia. PARTICIPANTS: 2725 subjects completed questionnaires, including 1128 men and 1258 women aged 18-59 years. MEASUREMENTS: Consumption categories from AUDIT quantity/frequency items: (1) non-drinkers (no alcohol in the past year), (2) occasional drinkers (monthly or less), (3) lower-level drinkers (up to 14 standard drinks per week for men and seven for women), (4) higher-level drinkers (up to 28 and 14 standard drinks per week, respectively), and (5) those drinking at hazardous or harmful levels (over 28 and 14 standard drinks per week, respectively). Goldberg and DSSI/sAD depression and anxiety scales. A range of demographic, socio-economic, socio-environmental and personality factors. FINDINGS: Non-drinkers were more likely than lower-level drinkers to have low status occupations, poor education, current financial hardship, poor social support and recent stressful life events, and scored lower on extraversion, fun-seeking and drive. Many of these characteristics also applied to hazardous/harmful drinkers. In multivariate models, these risk factors accounted for a substantial part of the higher depression and anxiety scores of non-drinkers and occasional drinkers relative to lower-level drinkers. CONCLUSIONS: Abstainers have a range of characteristics known to be associated with anxiety, depression and other facets of ill health, and these factors may contribute significantly to their elevated levels of depression and anxiety.

Adolescent↗
PubMed2000

Australia's mental health: an overview of the general population survey.

OBJECTIVES: The objectives of this study were to estimate the 1-month and 1-year prevalence of mental disorders in the Australian adult population; to determine the amount of disablement associated with this; and to determine the use of health and other services by persons with common mental disorders. METHOD: For the Adult Survey, a household sample of 10600 persons aged 18 years and over were interviewed across Australia by experienced field staff of the Australian Bureau of Statistics. This was 78% of the target sample. The interview consisted of the composite international diagnostic interview in its automated presentation (CIDI-A) and other components to determine disablement, use of services and satisfaction with services received. The diagnostic classifications used in the analyses were both ICD-10 and DSM-IV. Only the results from ICD-10 are reported here. RESULTS: A total of 17.7% of the sample had one or more common mental disorders, anxiety, depression, alcohol or substance abuse and neurasthenia. This morbidity was associated with considerable disablement in daily life: 3 days of impaired social role performance in the previous 4 weeks, compared with 1 day for the general population. Of all cases, 64.6% had had no contact with health services in the previous year; 29.4% had seen GPs and 7.5% had seen psychiatrists. CONCLUSION: Australia now has its own national estimates of psychiatric morbidity. The morbidity is associated with considerable disablement, but most of it is untreated. General practitioners encounter by far the largest proportion of those reaching services.

Adolescent↗
PubMed2000

The Australian National Survey of Mental Health and Well-Being. Common psychological symptoms and disablement.

BACKGROUND: The mental health of populations can be represented by case prevalence rates and by symptom scales. Scales have the advantage of identifying sub-syndromal levels of distress, which may be common and associated with considerable disability. AIMS: To examine the distribution of common psychological symptoms and associated disablement in the Australian population. METHOD: A household sample of 10,641 individuals representative of the adult population of Australia was interviewed using the Composite International Diagnostic Interview and completed scales measuring recent symptoms and disablement. RESULTS: Symptom scales showed similar associations with socio-economic variables as did diagnoses, although only a small amount of variance in symptom levels was explained by these variables. Considerable disablement was associated with symptom levels indicating distress but not reaching levels for formal diagnoses of anxiety or depression. CONCLUSIONS: Symptom scales provide parsimonious measures of psychological distress and are appropriate for use in large-scale surveys of mental health and disablement.

Adolescent↗