Shine: further notes of discord.
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Biomedical subjects
Publications and source records attributed to G Walter.
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OBJECTIVE: To examine the extent to which clinicians from different cultures agree when rating the quality of a child's family environment and the effect of country, language, and training factors on these ratings. METHOD: Eighty-seven health professionals from Malaysia, Spain, Australia, Indonesia, the United States, Denmark, and Singapore rated 7 case vignettes using the Global Family Environment Scale. Half (54%) were psychiatrists. One quarter (26%) performed the ratings after attending a training session, the rest (n = 64, 74%) after reading a training manual. RESULTS: Overall, interrater agreement (intraclass r) was 0.84 (95% confidence interval: 0.68-0.96). There were no significant differences in agreement according to country, language, training, or professional group, although there were country differences in the ratings given to 2 vignettes. The majority of raters found the description of the anchor points (86%), training manual (95%), and case vignettes (97%) clear. CONCLUSIONS: Clinicians from different cultures seem to be able to make global ratings of the quality of the family environment that are reliable and consistent when using case vignettes. This can be achieved with little training. Global ratings of the quality of the family environment may be a useful tool in mental health research and clinical work.
Connatal bacterial pneumonia is common in neonates. Animal studies and initial clinical reports indicate that surfactant dysfunction is involved in the pathophysiology of severe neonatal pneumonia. Since respiratory distress syndrome and connatal pneumonia may be difficult to differentiate in the first hours of life, neonates with respiratory failure due to bacterial infections might receive surfactant. Under such conditions surfactant components might be catabolized by bacteria and promote bacterial growth. We therefore investigated the influence of three modified natural (Curosurf, Alveofact, and Survanta) and two synthetic (Exosurf and Pumactant) surfactant preparations on the growth of bacteria frequently cultured from blood or tracheal aspirate fluid in the first days of life. Group B streptococci (GBS), Staphyloccocus aureus, and Escherichia coli were incubated in a nutrient-free medium (normal saline) for 5 h at 37 degrees C, together with different surfactants at concentrations of 0, 1, 10, and 20 mg/ml. With the exception of E. coli, incubation in saline alone led to a variable decrease in CFU. In the presence of Alveofact, Exosurf, and Pumactant the decline in bacterial numbers was less marked than in saline alone. Curosurf was bactericidal in a dose-dependent fashion for GBS and had a strong negative impact on the growth of a GBS subtype that lacked the polysaccharide capsule. In contrast, Survanta (10 and 20 mg/ml) significantly promoted the growth of E. coli, indicating that surfactant components may actually serve as nutrients. We conclude that bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. Further studies are necessary to elucidate the mechanisms behind our findings and to evaluate the effects of surfactant on bacterial growth in vivo.
The protein phosphatase 2A (PP2A) holoenzyme consists of a catalytic subunit, C, and two regulatory subunits, A and B. The PP2A core enzyme is composed of subunits A and C. Both the holoenzyme and the core enzyme are similarly abundant in heart tissue. Transgenic mice were generated expressing high levels of a dominant negative mutant of the A subunit (A delta 5) in the heart, skeletal muscle, and smooth muscle that competes with the endogenous A subunit for binding the C subunit but does not bind B subunits. We found that the ratio of core enzyme to holoenzyme was increased in A delta 5-expressing hearts. Importantly, already at day 1 after birth, A delta 5-transgenic mice had an increased heart weight-to-body weight ratio that persisted throughout life. Echocardiographic analysis of A delta 5-transgenic hearts revealed increased end-diastolic and end-systolic dimensions and decreased fractional shortening. In addition, the thickness of the septum and of the left ventricular posterior wall was significantly reduced. On the basis of these findings, we consider the heart phenotype of A delta 5-transgenic mice to be a form of dilated cardiomyopathy that frequently leads to premature death.
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1. In vivo ATP synthesis rates were measured in the human medial gastrocnemius muscle during high intensity exercise using localized 31P-magnetic resonance spectroscopy (31P-MRS). Six-second localized spectra were acquired during and following a 30 s maximal voluntary rate exercise using a magnetic resonance image-guided spectral localization technique. 2. During 30 s maximal voluntary rate exercise, ATPase fluxes were predominantly met by anaerobic ATP sources. Maximal in vivo glycogenolytic rates of 207 +/- 48 mM ATP min-1 were obtained within 15 s, decreasing to 72 +/- 34 mM ATP min-1 by the end of 30 s. In contrast, aerobic ATP synthesis rates achieved 85 +/- 2 % of their maximal capacity within 9 s and did not change throughout the exercise. The ratio of peak glycolytic ATP synthesis rate to maximal oxidative ATP synthesis was 2.9 +/- 0.9. 3. The non-Pi, non-CO2 buffer capacity was calculated to be 27.0 +/- 6. 2 slykes (millimoles acid added per unit change in pH). At the cessation of exercise, Pi, phosphomonoesters and CO2 were predicted to account for 17.2 +/- 1.5, 5.57 +/- 0.97 and 2.24 +/- 0.34 slykes of the total buffer capacity. 4. Over the approximately linear range of intracellular pH recovery following the post-exercise acidification, pHi recovered at a rate of 0.19 +/- 0.03 pH units min-1. Proton transport capacity was determined to be 16.4 +/- 4.1 mM (pH unit)-1 min-1 and corresponded to a maximal proton efflux rate of 15.3 +/- 2.7 mM min-1. 5. These data support the observation that glycogenolytic and glycolytic rates are elevated in vivo in the presence of elevated Pi levels. The data do not support the hypothesis that glycogenolysis follows Michealis-Menten kinetics with an apparent Km for [Pi] in vivo. 6. In vivo -measured ATP utilization rates and the initial dependence on PCr and glycolysis were similar to those previously reported in in situ studies involving short duration, high intensity exercise. This experimental approach presents a non-invasive, quantitative measure of peak glycolytic rates in human skeletal muscle.
Proteins translate genomic sequence information into function, enabling biological processes. As a complementary approach to gene expression profiling on cDNA microarrays, we have developed a technique for high-throughput gene expression and antibody screening on chip-size protein microarrays. Using a picking/spotting robot equipped with a new transfer stamp, protein solutions were gridded onto polyvinylidene difluoride filters at high density. Specific purified protein was detected on the filters with high sensitivity (250 amol or 10 pg of a test protein). On a microarray made from bacterial lysates of 92 human cDNA clones expressed in a microtiter plate, putative protein expressors could be reliably identified. The rate of false-positive clones, expressing proteins in incorrect reading frames, was low. Product specificity of selected clones was confirmed on identical microarrays using monoclonal antibodies. Cross-reactivities of some antibodies with unrelated proteins imply the use of protein microarrays for antibody specificity screening against whole libraries of proteins. Because this application would not be restricted to antigen-antibody systems, protein microarrays should provide a general resource for high-throughput screens of gene expression and receptor-ligand interactions.
Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by defects of the ventral midline, including hypertelorism, cleft lip and palate, heart defects, and mental retardation. We recently identified the gene responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a member of the RING finger family. These proteins are characterized by an N-terminal tripartite protein-protein interaction domain and a conserved C terminus of unknown function. Unlike other RING finger proteins for which diverse cellular functions have been proposed, the function of MID1 is as yet undefined. By using the green fluorescent protein as a tag, we show here that MID1 is a microtubule-associated protein that influences microtubule dynamics in MID1-overexpressing cells. We confirm this observation by demonstrating a colocalization of MID1 and tubulin in subcellular fractions and the association of endogenous MID1 with microtubules after in vitro assembly. Furthermore, overexpressed MID1 proteins harboring mutations described in OS patients lack the capability to associate with microtubules, forming cytoplasmic clumps instead. These data give an idea of the possible molecular pathomechanism underlying the OS phenotype.
OBJECTIVE: The aim of this study was to assess the experience, knowledge and attitudes of mental health staff regarding patients' problematic drug and alcohol use in order to provide direction for planned drug and alcohol education. METHOD: A 47-item questionnaire was developed and individually posted to all mental health staff employed by Central Sydney Area Health Service (n = 536). RESULTS: Three hundred and thirty-eight (63%) staff members completed the questionnaire. Thirty-six percent of respondents had received drug and alcohol training and 41% had drug and alcohol work experience. Drug and alcohol training and work experience were associated with increased drug and alcohol knowledge. Respondents' perception of their knowledge and competence was positively correlated with their actual knowledge. Most staff reported having regular contact with patients with psychotic illnesses and drug and alcohol problems. The majority considered the management of this patient group difficult and currently inadequate. Seventy percent believed that as mental health professionals they had a role to play in the management of their patients' drug and alcohol problems. Almost all (95%) were willing to participate in further education and training in this area. CONCLUSIONS: Mental health staff are often confronted with drug and alcohol problems in patients with psychotic illnesses. They perceive a need for drug and alcohol education and training specific to the management of these patients. Future research will need to evaluate outcomes of education and training programs for both staff and patients.
OBJECTIVE: The aim of this paper is to inform psychiatrists about the basic principles, terminology, schools of thought, efficacy, safety and regulatory issues regarding herbal treatments for mental illness. METHOD: Information was obtained by computerised and manual searching of medical and botanical data bases, and by discussions with experts in herbal medicine and regulatory aspects of the pharmaceutical industry. RESULTS: Herbal medicines are commonly used in developed and developing countries for psychiatric illness. The main schools of herbal medicine in Australia are Western herbal medicine, traditional Chinese medicine and 'Ayurveda' (Indian herbal medicine). Herbs used for psychiatric or neurological disorders are termed 'nervines'. Three nervines which have attracted considerable attention recently are St John's Wort, Gingko biloba and Valeriana officinalis. In Australia, most herbal drugs are classed as 'listed drugs' which are required to satisfy less rigorous safety and efficacy criteria than 'registered drugs'. The popularity of herbal remedies has a number of clinical and research implications for psychiatry. CONCLUSIONS: Psychiatrists should not endorse treatments that are unsupported by sound research, nor remain ignorant about alternative approaches to mental illness. The extent of use of herbal treatments for mental illness suggests that psychiatrists should become more knowledgeable about developments in this area.
Herbal remedies are commonly used for psychiatric problems, but there is virtually no data about the use of these substances by young persons or by patients in treatment. Four adolescents who used St. John's Wort while under psychiatric care are described. Three of the patients had been reluctant to reveal this to their psychiatrist, believing the doctor had no interest in alternative medicine or would disapprove. Patient beliefs that prescribed medication has limitations and that natural products are safe contributed to the use of herbal remedies. The cases raise a number of issues, including the need for clinicians to routinely ask patients about alternative medicine use, to learn more about these treatments, and to discuss these approaches objectively with patients.
OBJECTIVE: To ascertain the experience, knowledge, and attitudes regarding electroconvulsive therapy (ECT) of persons who received the treatment in adolescence. METHOD: A 53-item survey was administered by telephone to persons who received ECT before the age of 19 years in the Australian state of New South Wales between 1990 and 1998. RESULTS: Twenty-six patients were interviewed. Experiences and opinions about ECT were generally positive. Fifty percent stated ECT had been helpful. Approximately three quarters believed their illness was worse than either ECT or pharmacotherapy. Frequencies of recalled side effects with ECT and medication were similar. Some patients perceived deficiencies in the consent process. A slight majority had attempted to conceal the history of ECT treatment. The vast majority considered ECT a legitimate treatment and, if medically indicated, would have ECT again and would recommend it to others. CONCLUSIONS: The findings are consistent with and complement evidence showing ECT to be an effective and safe treatment for seriously ill adolescents. The mostly favorable experiences and attitudes reported by interviewees will be reassuring to adolescent patients, their families, and treating health professionals when ECT is being considered.
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The core enzyme of protein phosphatase 2A is composed of a regulatory subunit A and a catalytic subunit C. It is controlled by three types of regulatory B subunits (B, B', and B") and by tumor (T) antigens, which are unrelated by sequence but bind to overlapping regions on the A subunit. To find out whether the different B subunits and T antigens bind to identical or distinct amino acids of the A subunit, mutants were generated and their abilities to bind B subunits and T antigens were tested. We found that some amino acids are involved in the binding of all types of B subunits, whereas others are specifically involved in the binding of one or two types of B subunits. T-antigen-binding specificity does not correlate with that of a particular type of B subunit.
The study assessed the experience, knowledge, and attitudes of parents of adolescents who had been treated with electroconvulsive therapy (ECT) about that treatment. Twenty-eight parents were interviewed. Overall, their opinions about ECT were favorable. Seventeen of 28 parents thought that ECT had been helpful. If ECT was recommended by a doctor, the vast majority of parents would support a decision for their child to have the treatment again and would advise others to consider it.
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