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Biomedical subjects

W Wallace

Publications and source records attributed to W Wallace.

At least 19 recordsLinked to original sources
PubMed2005

Risk of silicosis in cohorts of Chinese tin and tungsten miners and pottery workers (II): Workplace-specific silica particle surface composition.

BACKGROUND: It is hypothesized that surface occlusion by alumino-silicate affects the toxic activity of silica particles in respirable dust. In conjunction with an epidemiological investigation of silicosis disease risk in Chinese tin and tungsten mine and pottery workplaces, we analyzed respirable silica dusts using a multiple-voltage scanning electron microscopy-energy dispersive X-ray spectroscopy (MVSEM-EDS). METHODS: Forty-seven samples of respirable sized dust were collected on filters from 13 worksites and were analyzed by MVSEM-EDS using high (20 keV) and low (5 keV) electron beam accelerating voltages. Changes in the silicon-to-aluminum X-ray line intensity ratio between the two voltages are compared particle-by-particle with the 90th percentile value of the same measurements for a ground glass homogeneous control sample. This provides an index that distinguishes a silica particle that is homogeneously aluminum-contaminated from a clay-coated silica particle. RESULTS: The average sample percentages of respirable-sized silica particles alumino-silicate occlusion were: 45% for potteries, 18% for tin mines, and 13% for tungsten mines. The difference between the pottery and the metal mine worksites accounted for one third of an overall chi-square statistic for differences in change in measured silicon fraction between the samples. CONCLUSION: The companion epidemiological study found lower silicosis risk per unit cumulative respirable silica dust exposure for pottery workers compared to metal miners. Using these surface analysis results resolves differences in risk when exposure is normalized to cumulative respirable surface-available silica dust.

Ceramics↗
PubMed2005

Bleeding gastric varices--a rare complication of ovarian cancer.

Splenic venous hypertension (or 'left-sided portal hypertension') is a rare underlying cause of gastro-oesophageal varices. Ovarian carcinoma recurring beyond 10 years, following primary treatment with no interval disease, is also a rare occurrence. We report an unusual case of bleeding gastric varices secondary to splenic venous obstruction as a result of metastatic ovarian carcinoma. This occurred 21 years following surgery and adjuvant chemotherapy for primary ovarian carcinoma. To our knowledge, until now, there have been no reported cases of splenic venous hypertension due to ovarian carcinoma. This case report illustrates the successful emergency management of this condition by splenectomy, with complete resolution of varices confirmed endoscopically at 6 weeks. It is followed by a brief discussion regarding varices due to splenic venous hypertension.

Aged↗
PubMed2004

Comparison of inhibitory effects of oxygen radicals and calf serum protein on surfactant activity.

The effects of the reactive oxygen species (ROS) superoxide anion (O2*-) and hydroxyl radical (*OH) on the surface tension lowering properties of bovine lipid extract surfactant (BLES) were compared to the effects of calf serum protein (CSP) in a captive bubble surfactometer (CBS). O2*- was generated from xanthine/xanthine oxidase (X/XO), and *OH was generated by the Fenton reaction. ROS were demonstrated by electron spin resonance (ESR) using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap. Lipid peroxidation was measured using the thiobarbituric acid method. *OH had broad inhibitory effects on surface tension parameters, including adsorption, minimum surface tension, percentage film area change and film compressibility. O2*- showed inhibitory effects on adsorption, film area change and film compressibility but had no significant effect on minimum surface tension. Both O2*- and *OH treatment were associated with a large 'squeezeout' plateau around 20-25 mN/m in the surface tension-area relation, indicating poor film organization during the compression phase. At the concentrations used, ROS were associated with lipid peroxidation of BLES, which also demonstrated radical scavenging properties. Calf serum protein produced inhibitory effects on adsorption, minimum surface tension and percentage film area change that were quantitatively similar to those produced by *OH. The effects on film compression were significantly greater and qualitatively different from those seen with either O2*- or *OH. We conclude that the inhibition of BLES surface activity by ROS and inhibitory proteins can be distinguished in the captive bubble surfactometer and, particularly, by changes in the film compressibility modulus.

Adsorption↗
PubMed2001

A workingperson's guide to deconvolution in light microscopy.

Thefluorescence microscope is routinely used to study cellular structure in many biomedical research laboratories and is increasingly used as a quantitative assay system for cellular dynamics. One of the major causes of image degradation in the fluorescence microscope is blurring. Deconvolution algorithms use a model of the microscope imaging process to either subtract or reassign out-of-focus blur. A variety of algorithms are now commercially available, each with its own characteristic advantages and disadvantages. In this article, we review the imaging process in the fluorescence microscope and then discuss how the various deconvolution methods work. Finally, we provide a summary of practical tips for using deconvolution and discuss imaging artifacts and how to minimize them.

Algorithms↗
PubMed1999

Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression.

We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h-APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We were able to infect PC12 cells with very high efficiency because approximately 90% of the cells were cytochemically positive for beta-galactosidase activity when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells infected with adenovirus containing h-APP cDNA showed high-level transcription and expression of h-APP as measured by reverse transcriptase-polymerase chain reaction and Western immunoblot analyses, respectively. Intracellular and extracellular levels of h-APP were elevated approximately 17-and 24-fold in cultures infected with recombinant adenovirus containing wild-type mutant and 13- and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures infected with antisense h-APP or null adenovirus. H-APP levels were maximal 3 days after infection. Overexpression of V642F mutant h-APP in PC12 cells and hippocampal neurons resulted in about a twofold increase in death compared with overexpression of wild-type h-APP. These results demonstrate the usefulness of recombinant adenoviral mediated gene transfer in cell culture studies and suggest that overexpression of a familial Alzheimer's disease mutant APP may be toxic to neuronal cells.

Adenoviridae↗
PubMed1998

Beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants.

The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-G) and APP(693E-Q) (at A beta21 and A beta22, respectively) which are found in familial Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function.

Adenosine Diphosphate↗
PubMed1998

Evaluation of a bicycle skills training program for young children: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a skills training program in improving safe cycling behavior, knowledge, and attitudes in young children. METHODS: Grade 4 children from six elementary schools in East York (a borough of Metropolitan Toronto) participated. The intervention--playground based instruction on bicycle handling skills by certified instructors--was randomly allocated to three schools. Altogether 141 children participated: 73 in the intervention group and 68 in the control group, with follow up evaluations available on 117 (83%). The primary outcome was safe cycling behavior (straight line riding, coming to a complete stop, and shoulder checking before a left turn). A self report questionnaire collected data on knowledge and attitudes. Baseline assessments were made in June, with follow up evaluations in September, 1995. RESULTS: The prevalence of safe cycling behaviors at follow up in the intervention and control groups respectively, were: straight line riding (90% v 88%; p = 0.782), coming to a complete stop (90% v 76%; p = 0.225), and shoulder checking (0% v 2%; p = 1.000). Over time (from baseline to follow up) children in both groups were more likely to maintain straight line riding, less likely to ride on the sidewalk, and less likely to consider that a car had more right to the road. CONCLUSIONS: This brief skills training program was not effective in improving safe cycling behavior, knowledge, or attitudes among grade 4 children.

Accident Prevention↗
PubMed1995

An unusual case of laryngeal pseudotumour.

A pseudotumour represents a lesion that masquerades as a malignant neoplasm. We present an unusual case where the appearance of a tumour was the result of chronic inflammation stimulated by the presence of food matter. This inflammatory reaction resulted in upper airway obstruction associated with a mass lesion and vocal fold palsy.

Aged↗
PubMed1994

A comparison of multiplex and simplex families with Alzheimer's disease/senile dementia of Alzheimer type within a well defined population.

A study was made on 150 clinically demented patients presenting at autopsy at Umeå University Hospital in Sweden. In 90 of the cases dementia was considered to be primary in nature and of these forty six per cent (41 cases), fulfilled both the clinical and histopathological criteria for the diagnosis of Alzheimer's disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41 AD/SDAT cases were then studied, and a family history obtained through interviews with multiple family informants and from civil and medical records. Additional diseased family members suffering from progressive dementia (multiplex families) were observed in 12 probands out of 41 (29%). Multiplex families exhibited similar clinical and histopathological characteristics as simplex families containing a single affected individual. The secondary cases in the multiplex families exhibited similar demographic and clinical characteristics as the probands. 39% of the multiplex and 14% of the simplex cases had an early age of onset of the disease, that was under 65 years. The overall prevalence of progressive dementia disorders in the 41 families was 5.9%. The prevalence of a progressive dementia disorder was 11% in the multiplex families (14% for the early onset cases) and 3.5% in the simplex families (2% for the early onset cases). The prevalence of progressive dementia disorder for family members who had passed the mean age of the onset of the disease for their family, was 45% for multiplex and 18% for simplex families. Furthermore the incidence rate for dementia was significantly higher (p < 0.005) in multiplex families (5.5 per 1,000 person years) when compared to simplex families (2.5 per 1,000 person years). No differences could be seen in parental age at birth of the diseased when comparing the two sets of families. However in multiplex families the duration of the disease was significantly (p < 0.025) shorter, in subjects with parental age at birth over 35 years compared to those with a parental age under 35 years. The multiplex families contained significantly (p < 0.025) larger sibships; and showed a significantly lower age of onset for the disease (p < 0.001), and a significantly longer duration of disease (p < 0.05) compared to the simplex families. A significant intra familial correlation of age at disease onset was observed in both sets of the families.

Age of Onset↗
PubMed1994

Characterization of gene expression in the cerebral cortices of rat brains containing subcortical lesions.

Neurotoxic lesion of the nucleus basalis of Meynert in the rat brain, which results in the loss of subcortical cholinergic innervation to the cerebral cortex, is an animal model for the cortical cholinergic deficits that are characteristic of Alzheimer's disease. Previously, we have shown that amyloid precursor protein is induced in the cortex in response to this disrupted innervation. We have investigated the synthesis and accumulation of proteins in lesioned versus control cortices. Total proteins from cortices were separated by high resolution two-dimensional gel electrophoresis and visualized by silver stain. Of the greater than 1,000 polypeptides examined, only one exhibited a consistent alteration in the lesioned sample. This unidentified protein (Mr 34 kD, pI 5.5) was normally present in scant amounts but was virtually absent in the lesioned cortex (0.056% total integrated density (TID) and 0.008% TID, respectively; p < 0.04). To investigate gene expression more directly, polysomes purified from lesioned and control cortices were assayed in vitro. Examination of [35S] incorporation into translation products by two-dimensional gels and autoradiography revealed three newly synthesized polypeptide differences in the lesioned samples. One protein (M(r) 47 kD, pI 6.1) exhibited elevated levels with the lesion (0.05% to 0.16%; p = 0.02) while two other proteins (M(r) 34 kD, pI 5.5, and M(r) 33 kD, pI 5.7) exhibited reduced levels (0.20% to 0.04%, p < 0.02, and 0.34% to 0.12%, p = 0.04, respectively).

Animals↗
PubMed1993

Using the subcortically lesioned rat cortex to understand the physiological role of amyloid precursor protein.

Alzheimer's disease pathology is characterized by the presence of neuritic plaques and neurofibrillary tangles and specific neurotransmitter deficits in the cortex and hippocampus. Advances in the understanding of Alzheimer's disease have been hampered by the absence of appropriate animal model systems. Most in vivo rodent models have turned to aged animals, animals with experimentally induced lesions of various neurotransmitter systems, animals with pharmacologically induced neurotransmitter perturbations, and mice made transgenic for genes related to amyloid precursor protein. These models have been useful for the investigation of some discrete aspects of Alzheimer's disease, including deficits in forebrain cholinergic activity and the resulting cognitive deficits. However, none of these models have led to the development of the principal neuropathological hallmarks of Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Furthermore, the relationship, if any, between the reduction of neurotransmitter activity and the formation of neuritic plaques and neurofibrillary tangles is unknown. The subcortically lesioned rat model system which we have used approximates the cortical neurotransmitter and the cognitive deficits of Alzheimer's disease. We have recently found that these same subcortical neurotransmitter system lesions alter the expression of amyloid precursor protein, the precursor of beta amyloid peptide, which is the principal component of neuritic plaques. Loss of functional subcortical innervation by either permanent lesions or transient inhibition of cortical neurotransmitter (acetylcholine) release resulted in the induction of amyloid precursor protein in the cortex. The induction was rapid and persistent with the permanent lesions or reversible with the transient inhibition. Lesions cholinergic, serotonergic,and adrenergic neurotransmitter systems all resulted in the induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

The relationship between self-esteem and depression in obese children.

It has been suggested that obese children have increased problems with self-esteem and depression when compared to the normal pediatric population. Fifty-one consecutive patients enrolled in a hospital based weight management program received the CDI and the PHSCS as part of their initial evaluation. There were 24 males and 27 females with ages ranging from 5-17 years and BMI (kg/m2) of 22-63 (mean 33.3). Results of the CDI were classified into three groups. Children with CDI scores greater than 13 were classified as depressed (n = 16). Scores between 9 and 12 were considered borderline depression (n = 11). Scores less than 9 were considered normal (n = 24). The children in the depressed and borderline groups were significantly different from the children in the normal group in their level of self-esteem. As depression increased, self-esteem decreased, indicating an inverse relationship between self-esteem and depression. Depressed and borderline depressed children were also more anxious (i.e., nervous, worried) and had more perceived behavior problems (increased frequency of punishment, difficulty obeying orders) than the normal group. They also had fewer interests in school and felt their physical appearance was not acceptable. The depressed group's scores were significantly lower on the happiness and popularity scales of the PHSCS than the normal group. Scores on the CDI did not correlate with age, race, sex, Tanner stage, socioeconomic status, or body mass index. In this study obese pediatric patients showed significant depression and lowered self-esteem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Heat-shocked neuronal PC12 cells reveal Alzheimer's disease--associated alterations in amyloid precursor protein and tau.

The Alzheimer's disease (AD) brain contains many abnormal protein modifications. These include the abnormal processing of amyloid precursor protein (APP) to form the amyloidogenic beta/A4 peptide and the abnormal phosphorylation of tau to form A68, the major constituent of the neurofibrillary tangle. In addition, many of the biochemical alterations found in the AD brain are also found in heat-shocked or stressed cells. We used heat-shocked neuronal PC12 cells to investigate the effects of stress on APP and tau. We found that by simply exposing neuronal PC12 cells to an elevated temperature (45 degrees C) for 30 minutes, they exhibited several features characteristic of the heat shock response. These included a 45% reduction in total protein synthesis, the induction of heat shock protein (hsp) 72, and increased phosphorylation of the protein synthesis initiation factor eIF-2 alpha. The heat-shocked cells also exhibited alterations in the metabolism and phosphorylation of APP. Under heat shock conditions, we found two additional APP-like polypeptides not present in controls and a significant decrease in the phosphorylation state of APP. We also found that an A68-like protein is formed in neuronal PC12 cells when subjected to elevated temperature. This A68-like protein was formed with heat shock even in the absence of protein synthesis, suggesting that its production occurred post-translationally. The tau/A68 polypeptides were identified as phosphoproteins, and the phosphorylation of tau to form A68 was reversed with recovery of the cells from heat shock. Immunoprecipitation of lysates from heat shocked cells with antibodies to hsp72/73 resulted in co-precipitation of tau, but not A68 with hsp72 indicating a stable complex formation between these two proteins. These results suggest that heat shock proteins may play either a protective or promoting role in the formation of A68 and/or the amyloidogenic C-terminal fragment of APP.

Alzheimer Disease↗
PubMed1993

Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.

Lesions of the cholinergic nucleus basalis of Meynert elevate the ex vivo synthesis of beta amyloid precursor protein (beta-APP) in the cerebral cortex, a major projection region. We have found that this elevation is reflected by increased levels of beta-APP mRNA. The induction is rapid (occurring 60 min after placement of the lesion) and persistent (remaining for at least 45 days after lesioning). Two other subcortical lesions, which result in reductions of cortical adrenergic and serotonergic innervation, similarly induced cortical beta-APP. The beta-APP induction is reversible and does not require loss of the subcortical neurons. Infusion of lidocaine, a calcium antagonist that disrupts neurotransmitter release, into the nucleus basalis of Meynert leads to the temporary reduction of released acetylcholine in the cortex. In this model, beta-APP mRNA levels are elevated shortly after the infusion of lidocaine (90 min) but return to preinfusion levels 7 days after the lidocaine treatment. However, metabolic stresses of the brain, including chronic physostigmine, glucocorticoid, and diabetogenic treatments, fail to induce the beta-APP response. These results suggest that the induction of beta-APP is a specific response to the loss of functional innervation in the cortex. Importantly, these studies show that cortical beta-APP is induced by lesions that mimic the neurochemical deficits most frequently observed in Alzheimer disease.

5,7-Dihydroxytryptamine↗
PubMed1993

Altered expression and phosphorylation of amyloid precursor protein in heat shocked neuronal PC12 cells.

The pathology of the Alzheimer's disease (AD) brain, including amyloid plaques, neurofibrillary tangles and neuronal degeneration, indicates that neurons affected by AD exist under conditions of stress. In fact, the brains of AD patients undergo many changes classically associated with the heat shock response, which is one form of a stress response. These changes include reduced protein synthesis, disrupted cytoskeleton, increased number of proteins associated with ubiquitin, and the induction of heat shock proteins. To investigate the response of neurons to stress, we examined neuronal PC12 cells incubated at either 37 degrees C (control cells) or 45 degrees C (heat-shocked cells). After a 30 min exposure at 45 degrees C, the heat-shocked cells exhibited several features characteristic of the classical heat shock response including a 45% reduction in total protein synthesis, the induction of heat shock protein 72, and an increased phosphorylation of the protein synthesis initiation factor eIF-2 alpha. We used this cellular model system to study the neuronal response to stress specifically focusing on protein synthesis elongation factor 2 (EF-2) and the Alzheimer's amyloid precursor protein (APP), the precursor form of beta-amyloid peptide. Hyperphosphorylation of EF-2 has been observed in the neocortex and hippocampus of AD brain. However, in our system, we find no hyperphosphorylation of EF-2 in response to heat shock. Heat-shocked neuronal PC12 cells exhibited two additional APP-like polypeptides not present in controls. We also found a significant decrease in the phosphorylation state of APP in response to heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Protein Precursor↗
PubMed1993

Reversible phosphorylation of tau to form A68 in heat-shocked neuronal PC12 cells.

A68, the primary protein constituent of Alzheimer's disease-associated neurofibrillary tangles, is an abnormally phosphorylated form of the microtubule-associated protein tau. We find that A68 is formed in neuronal PC12 cells when the cells are subjected to a heat shock (45 degrees C for 30 min). A68 was identified by immunoprecipitation with two different anti-tau antibodies (tau-2 and Alz50). Upon separation by SDS-polyacrylamide gel electrophoresis, the tau immunoprecipitates from heat-shocked cells exhibited an additional polypeptide of reduced electrophoretic mobility (approximately 68 kDa) when compared to control cells. A68 was formed with heat shock in the presence of cycloheximide, suggesting that its production occurred by post-translational modification of existing polypeptides. The tau/A68 polypeptides were identified as phosphoproteins by incorporation of 32P into the immunoprecipitates. The phosphorylation of tau to form A68 was reversed with recovery of the intact cells from the heat shock. Finally, immunoprecipitation of lysates from heat-shocked cells with antibodies to heat shock protein (hsp) 72/73 resulted in co-precipitation of tau with hsp 72, which indicates a stable complex formation between these two proteins. On the other hand, A68 remained unassociated with hsp during the heat shock. These results suggest that tau is reversibly phosphorylated to form A68 in neuronal PC12 cells under conditions of stress.

Animals↗