Biomedical subjects
Publications and source records attributed to A Baker.
We report a case of a child with portal vein thrombosis presenting with protein losing enteropathy. Helater developed exocrine and endocrine pancreatic failure. This association has not been reported before.
The current study examined the impact on employee health and safety of changes to the roster system of an Australian coal mine. Absenteeism and incident frequency rate data were collected over a 33-month period that covered three different roster schedules, an 8-hour system, a 12-hour system and a 12-hour system incorporating unregulated overtime. The first change was implemented after consultation with the employee population, whereas the second was not. There were no significant negative effects of the 12-hour pattern, when compared to the 8-hour system. However, when unregulated and excessive overtime was introduced as part of the second round of changes, absenteeism rates were increased in one sector of the mine. The maintenance sector was subject to a significant increase in absenteeism rates, which may have been attributable to the excessive overtime required of the workers in that area. It is important that overtime be strictly monitored and that the employee population are involved in the process of roster change.
Peroxisomes are the cellular location of many antioxidants and are themselves significant producers of reactive oxygen species. In this report we demonstrate the induction of peroxisome biogenesis genes in both plant and animal cells by the universal stress signal molecule hydrogen peroxide. Using PEX1-LUC transgenic plants, rapid local and systemic induction of PEX1-luciferase could be demonstrated in vivo in response to physiological levels of hydrogen peroxide. PEX1-luciferase was also induced in response to wounding and to infection with an avirulent pathogen. We propose a model in which various stress situations that lead to the production of hydrogen peroxide can be ameliorated by elaboration of the peroxisome compartment to assist in restoration of the cellular redox balance.
Small DNA lesions such as oxidized or alkylated bases are repaired by the base excision repair (BER) pathway. BER includes removal of the damaged base by a lesion-specific DNA glycosylase, strand scission by apurinic/apyrimidinic endonuclease, DNA resynthesis and ligation. BER may be further subdivided into DNA beta-polymerase (beta-pol)-dependent single-nucleotide repair and beta-pol-dependent or -independent long patch repair subpathways. Two important enzymatic steps in mammalian single-nucleotide BER are contributed by beta-pol: DNA resynthesis of the repair patch and lyase removal of 5'-deoxyribose phosphate (dRP). Fibroblasts from beta-pol null mice are hypersensitive to mono-functional DNA-methylating agents, resulting in increases in chromosomal damage, apoptosis and necrotic cell death. Here we show that only the dRP lyase activity of beta-pol is required to reverse methylating agent hypersensitivity in beta-pol null cells. These results indicate that removal of the dRP group is a pivotal step in BER in vivo. Persistence of the dRP moiety in DNA results in the hypersensitivity phenotype of beta-pol null cells and may signal downstream events such as apoptosis and necrotic cell death.
Caspases are cysteine proteinases that play a critical role in the execution phase of apoptosis. The active site cysteine residue must be reduced for caspase activity. Thioredoxins are redox proteins that catalyze the reduction of cysteine residues. We have examined the ability of various recombinant human thioredoxins to activate caspase-3. The EC(50) for caspase-3 activation by reduced thioredoxin-1 was 2.5 microM, by reduced glutathione 1.0 mM and by dithiothreitol 3.5 mM. A catalytic site redox-inactive mutant thioredoxin-1 was almost as active as thioredoxin-1 in activating caspase-3. Caspase activation was shown to correlate with the number of reduced cysteine residues in the thioredoxins. Reduced insulin and serum albumin were as effective on a molar basis as thioredoxin-1 in activating caspase-3. Thus, caspase-3 activation is not a specific effect of thioredoxins but is a property shared by other reduced proteins.
OBJECTIVE: To evaluate variables associated with quality of life (QOL) in dementia residents in a long-term care facility using a recently standardized and validated dementia-specific QOL scale (ADRQL). METHOD: A cross-sectional, case-control design was employed using validated scales to assess dementia-related symptomatology. Thirty-two facility staff members were interviewed to assess the QOL of 120 patients meeting DSM-IV for dementia criteria residing in long-term care. RESULTS: ADRQL scores were higher in assisted living residents than in skilled nursing facility residents. In univariate analyses, worse orientation, greater physical dependency, depression, and treatment with anxiolytics were associated with lower ADRQL scores. In multivariate analyses, lower scores were associated with worse orientation, greater physical dependency, depression, and anxiolytic treatment. CONCLUSIONS: Residents exhibited better QOL than expected. Future longitudinal studies should address if reorientation, activity therapy, treatment of depression, and avoidance of benzodiazepines might improve QOL in this population. Interventions that might improve orientation and physical abilities, such as cholinomimetic therapies, psychosocial interventions, or behavioral strategies, should also be studied in future research on QOL.
BACKGROUND: Assisted living (AL) is the fastest growing segment of residential long-term care in the US. At least half of the estimated 1 million AL residents have dementia or cognitive impairment, with many AL facilities offering specialized dementia services. Little research has been done on the demographics, outcomes, or clinical variables of this population. METHODS: Participants were a cohort of 144 residents admitted to the AL unit of Copper Ridge, a specialized dementia-care facility. Comparison samples included 737 patients with dementia residing in other locations (home, nursing home, and other assisted living facilities). Selected measures of cognition, behavior, medical health, and function were taken at admission to AL and at 6-month intervals. RESULTS: When compared with residents of the dementia-specialized AL facility, dementia patients at home were younger, less cognitively impaired, and less likely to exhibit wandering, delusions, or aggression. Residents of a dementia-specialized nursing home had more cognitive impairment, greater medical comorbidity, and were more dependent on caregivers. The 2-year mortality rate in the dementia-specialized AL was 23%, significantly lower than rates reported for nursing homes. Primarily due to increasing care needs, most residents in the specialized AL relocated to a nursing home after a median stay of 10.9 months. Depression, falling, and wandering were significant predictors of the transition. CONCLUSION: Dementia-specialized AL facilities occupy a unique position in the long-term care continuum that is distinct from home-care and nursing home facilities. This research is the first step toward understanding the significant dementia population residing in assisted living.
Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end-stage liver disease due to a1-AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver transplantations were performed. All children are currently alive at a median followup of 40 months. Liver replacement provides the only definite treatment for children with end-stage liver disease associated with a1-AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.
BACKGROUND/AIMS: Liver disease in infancy has multiple etiologies. As reactive oxygen intermediates are involved in several types of tissue damage, we have investigated whether different forms of liver disease in infancy are associated with increased free radical generation, using an indirect approach in which superoxide dismutase (a free radical scavenger) activity is determined in the liver tissue. METHODS: A total of 48 liver biopsies performed at diagnosis were evaluated retrospectively. Nine infants had biliary atresia, eight Alagille syndrome, seven alantitrypsin deficiency and 12 cryptogenic hepatitis. As controls we studied 12 biopsies with normal histology obtained from seven children with portal vein thrombosis and five children who underwent biopsy for management reason but had no liver disease. Superoxide dismutase activity in liver biopsy specimens was measured using the cytochrome C method by spectrophotometry and expressed as U SOD/mg protein. RESULTS: Superoxide dismutase activity was significantly increased in biliary atresia (1.25 +/- 0.56 U SOD/mg protein, p<0.0001) and Alagille syndrome (1.31 +/- 0.56 U SOD/mg protein, p<0.0001) as compared with al-antitrypsin deficiency (0.75 +/- 0.3 U SOD/mg protein), neonatal hepatitis (0.72 +/- 0.37 U. SOD/mg protein) and normal controls (0.4 +/- 0.7 U. SOD/mg protein). The highest level of SOD activity was found, however, in control children with portal vein thrombosis (2.09 +/- 0.96 U SOD/mg protein; p<0.0001 as compared to the other groups). CONCLUSION: Superoxide dismutase, a key enzyme in free radical protection, is increased significantly in the liver tissue of infants with cholestatic liver disease due to bile duct damage and in children with portal vein thrombosis, suggesting that products of free radical reactions are involved in the pathogenesis of these disorders.
We describe 10 patients who developed a psoriatic skin eruption during either the acute or convalescent phase of Kawasaki disease. The skin eruption was pustular in 3 patients, but more typical psoriasiform skin lesions were seen in the remaining 7 patients. No patient has yet developed chronic psoriasis.
This study examined differences between vascular dementia (VaD) by the NINDS/AIRENS criteria and Alzheimer's disease (AD) on clinical grounds. A consecutive series of 517 patients with probable and possible VaD or AD were evaluated for cognitive, functional, and behavioral symptoms and separated into three subgroups by duration of dementia. These AD and VaD subgroups were then compared on a series of standardized clinical measures. The only consistent trends were for VaD patients to be more depressed, more functionally impaired, and less cognitively impaired within each disease duration subgroup. The authors conclude that there are few differences between clinically diagnosed VaD and AD. Subclassification of VaD into subgroups will improve the clinical utility of this nosologic entity.
Peroxisomes are eukaryotic organelles that perform diverse and variable functions. Although genetic studies in yeasts and mammals have identified approximately 20 genes (PEX genes) required for the biogenesis of this important organelle, biochemical studies of protein targeting and import have lagged behind and in many cases we have no idea of the function of the PEX gene products (peroxins). Using an import assay in vitro derived from sunflower cotyledon cells and recombinant proteins, we have obtained translocation intermediates on the peroxisome import pathway and are using cross-linking to identify interacting partners. We have also used antibodies raised against human PEX14 to inhibit the import of matrix proteins in this system. To obtain homologous antibodies for inhibition experiments, to immunoprecipitate cross-linked products and to enable us to study the import pathways of peroxins we have cloned and characterized plant orthologues of three PEX genes, PEX6, PEX10 and PEX14.
Since the discovery of self-cleavage and ligation activity of the group I intron, the expansion of research interest in catalytic nucleic acids has provided a valuable nonprotein resource for manipulating biomolecules. Although a multitude of reactions can be enhanced by this class of catalyst, including trans-splicing activity of the group I intron (which could be applied to gene correction), RNA-cleaving RNA enzymes or "ribozymes" hold center stage because of their tremendous potential for mediating gene inactivation. This application has been driven predominantly by the "hammerhead" and "hairpin" ribozymes as they induce specific RNA cleavage from a very small catalytic domain, allowing delivery either as a transgene expression product or directly as a synthetic oligonucleotide. Although advances in the development of RNA modifications have improved the biological half-life of synthetic ribozymes, their use is restricted by the mechanistic dependence on conserved 2'OH-moieties. Recently a new class of catalytic nucleic acid made entirely of DNA has emerged through in vitro selection. DNA enzymes or deoxyribozyme with extraordinary RNA cleavage activity has already demonstrated their capacity for gene suppression both in vitro and in vivo. These new molecules, although rivaling the activity and stability of synthetic ribozymes, are limited equally by inefficient delivery to the intracellular target RNA. The challenge of in vivo delivery is being addressed with the assessment of a variety of approaches in animal models with the aim of bringing these compounds closer to the clinic.
The membrane protein Pex14p is a key component of the protein import machinery of peroxisomes. Antibodies raised against human Pex14p recognise a 66 kDa protein in sunflower glyoxysomes (HaPex14p) and immunoprecipitate in vitro-translated Arabidopsis Pex14p (AtPex14p). These antibodies inhibit the ATP-independent binding to sunflower peroxisome membranes of peroxisome targeting signal type (PTS) 1- and PTS2-targeted matrix proteins, but not an integral membrane protein. These results suggest that Pex14p functions before the ATP-dependent step of peroxisome assembly.
AIM: A retrospective audit was carried out of a single advance surgical trainee's experience with laparoscopic appendicectomy, in an attempt to justify its ongoing utilization in the management of patients with this acute surgical presentation. RESULTS: Two hundred laparoscopic appendicectomies have been performed over the last four years on an intention-to-treat basis. Sixty-five per cent have been female, with an average population age of 24 years. There was a true appendicitis rate of 79%, with a conversion rate of 6%, and a mean operating time of 32 minutes. Complications have included intra-abdominal sepsis in three (1.5%) and postoperative ileus (1%). There have been no reported wound infections. The mean times to discharge were two days in the laparoscopic group and 3.7 days in the converted group. CONCLUSION: This study supports the utilization of laparoscopic appendicectomy as a safe and effective operation for surgical trainees to gain laparoscopic experience.
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Social scientists have long recognized that individuals subjected to traumatic events associated with military and political conflict experience dire psychological consequences. The systematic study of this phenomenon, however, could be considered a nascent event. Research on the psychological sequel of traumatic events (traumatology) is well-rooted in the recognition and development of posttraumatic stress disorder as a separate psychological disorder category. The early studies in this field focused mainly on adult populations. With the recent advent of involvement of children in military conflicts such as in Africa (e.g., Mozambique), the Middle East (e.g., Palestine, Lebanon), and Southeast Asia (e.g., Cambodia), psychologists have taken a keen interest in examining the psychological effects such conflicts reap on children. Hence, a growing but modest body of literature has been amassed within the past 20 years on the subject. This article is an attempt to synthesize this literature in order to examine the universal and culture-specific correlates of political and military trauma. Specifically, the article will focus on the psychological symptoms children display following their exposure to such traumatic events. Special emphasis will be placed on anxiety, phobic, psychosomatic, and depressive symptoms. More importantly, however, an examination will be made to ascertain which factors (e.g., psychosocial, cultural, and political) serve to shield (protect) or predispose (vulnerability) children to psychological dysfunction. Furthermore, the analyses presented will be gender specific. The article will attempt to delineate a paradigm that explains the relationship between trauma, culture, and personality. Although the article will examine studies from various regions, specific emphasis will be placed on the Palestinian experience.
Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.