Biomedical subjects

J Matheson

Publications and source records attributed to J Matheson.

At least 19 recordsLinked to original sources

PubMed2005

Membrane traffic in cytokinesis.

A crucial facet of mammalian cell division is the separation of two daughter cells by a process known as cytokinesis. An early event in cytokinesis is the formation of an actomyosis contractile ring, which functions like a purse string in the constriction of the forming furrow between the cells. Far less well characterized are the membrane-trafficking steps which deliver new membrane to the cell surface during the plasma membrane expansion known to accompany furrow formation. It is now clearly established that the plasma membrane at the cleavage furrow of mammalian cells has a distinct lipid and protein composition from the rest of the plasma membrane. This may reflect a requirement for both increased surface area during furrowing and for the co-ordinated delivery of intracellular signalling or membrane re-modelling activities to the correct spatial coordinates during cleavage. In this review, we discuss recent work within the area of membrane traffic and cytokinesis.

ADP-Ribosylation Factor 6↗

PubMed2001

Polymorphisms of the IL-1 gene complex in coal miners with silicosis.

BACKGROUND: Silicosis is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Pro-inflammatory cytokines, such as interleukin-1 (IL-1), play a key role in the development of silicosis by regulating mediators which are responsible for lung injury, inflammation, and potentially fibrosis. To study whether functional single nucleotide polymorphisms (SNPs) located in the regulatory elements of genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist (RA) cytokines are associated with silicosis, we examined 318 Caucasian cases confirmed histopathologically with pulmonary silicosis and 163 controls without any apparent inflammation or other pulmonary disease. METHODS: Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The proportion of the IL-1RA (+ 2018) allele 2 genotype was increased in miners with silicosis (0.27) compared to controls (0.16). The odds of being a case were 2.15 (CI = 1.4-3.3) times higher for subjects with at least one copy of allele 2. No statistically significant differences in the allelic frequencies or genotype distributions for IL-1alpha (+ 4845) or IL-1beta (+ 3953) were found between the control and disease groups. CONCLUSIONS: This is the first report showing an association between the IL-1RA (+ 2018) polymorphism and silicosis, and suggests that this polymorphism may confer increased risk for the development of the disease.

Adult↗

PubMed2001

Bilateral orbitomedial leucotomy for obsessive-compulsive disorder: a single-case study using positron emission tomography.

OBJECTIVE: The objective of this report is to correlate the clinical outcome of neurosurgery for obsessive-compulsive disorder (OCD) with regional cerebral glucose metabolic changes. CLINICAL PICTURE: The patient was a 37-year-old female patient with severe and intractable OCD. TREATMENT: The patient was treated with bilateral stereotactic lesions in the frontal white matter superior to the orbito-medial cortex. OUTCOME: She had a remarkable improvement in her obsessive-compulsive symptoms, which was sustained up to 3 years of follow up. A positron emission tomography (PET) scan performed 18 days after surgery demonstrated an obvious reduction of metabolism in the caudate head, anterior cingulate and orbital, medial and lateral prefrontal cortices and the thalamus. At 1 year postsurgery, metabolic rate was still reduced in the anterior cingulate gyrus, caudate and thalamus compared with preoperative baseline. The patient demonstrated no long-term cognitive effects of the surgery. CONCLUSIONS: This case supports some of the cortical-subcortical circuit dysfunction models of OCD and argues for the further evaluation of neurosurgery for the treatment of a severe and intractable disorder.

Adult↗

PubMed2000

Overview of immunotoxicology and current applications to respiratory diseases.

Immunotoxicology has been defined as the study of adverse effects on the immune system resulting directly from environmental, occupational, or therapeutic exposure to chemicals (including drugs), biological materials and, in certain instances, physiological factors, collectively referred to as agents. It encompasses immunosuppression, allergy, autoimmunity and inflammation.

Animals↗

PubMed2000

Arsenic mediates cell proliferation and gene expression in the bladder epithelium: association with activating protein-1 transactivation.

Although the mechanism of action has not yet been defined, epidemiological studies have demonstrated an association between elevated arsenic levels in drinking water and the incidence of urinary bladder transitional cell carcinomas. In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of exposure. This was accompanied by the accumulation of inorganic trivalent arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. AP-1 transactivation by arsenic also occurred in bladders of transgenic mice containing an AP-1 luciferase reporter. Consistent with these in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding in a human bladder epithelial cell line. Gene expression studies using RNase protection assays, reverse transcription-PCR, and cDNA microarrays indicated that arsenite alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells likely contributes to its ability to cause cancer.

Animals↗

PubMed2000

Educational differences in smoking: international comparison.

OBJECTIVE: To investigate international variations in smoking associated with educational level. DESIGN: International comparison of national health, or similar, surveys. SUBJECTS: Men and women aged 20 to 44 years and 45 to 74 years. SETTING: 12 European countries, around 1990. MAIN OUTCOME MEASURES: Relative differences (odds ratios) and absolute differences in the prevalence of ever smoking and current smoking for men and women in each age group by educational level. RESULTS: In the 45 to 74 year age group, higher rates of current and ever smoking among lower educated subjects were found in some countries only. Among women this was found in Great Britain, Norway, and Sweden, whereas an opposite pattern, with higher educated women smoking more, was found in southern Europe. Among men a similar north-south pattern was found but it was less noticeable than among women. In the 20 to 44 year age group, educational differences in smoking were generally greater than in the older age group, and smoking rates were higher among lower educated people in most countries. Among younger women, a similar north-south pattern was found as among older women. Among younger men, large educational differences in smoking were found for northern European as well as for southern European countries, except for Portugal. CONCLUSIONS: These international variations in social gradients in smoking, which are likely to be related to differences between countries in their stage of the smoking epidemic, may have contributed to the socioeconomic differences in mortality from ischaemic heart disease being greater in northern European countries. The observed age patterns suggest that socioeconomic differences in diseases related to smoking will increase in the coming decades in many European countries.

Adult↗

PubMed1999

Silent functional magnetic resonance imaging demonstrates focal activation in rapid eye movement sleep.

Functional imaging of human sleep has been performed with nuclear medicine methods, but MRI has been difficult to implement, in part because of the noise associated with echo-planar imaging as well as the difficulty in reading physiologic signals in the MRI environment. We describe a silent MR sequence that can record brain activation over many hours with simultaneous acquisition of an EEG. This shows activation of occipital cortex and deactivation of frontal cortex during REM sleep, in agreement with previous studies using other techniques. MRI-Sleep-REM sleep.

Adult↗

PubMed1999

Tumor necrosis factor alpha and toxicology.

The molecular cloning of a group of proteins, collectively referred to as cytokines, and including interleukins, chemokines, growth factors, colony stimulating factors, and tumor necrosis factors, has allowed for the increased understanding of the mechanisms for many disease processes as well as provided strategies for the development of novel therapies. Conceptually similar to hormones and peptides, this group of phylogenetically related molecules are also involved in various toxicological processes, including apoptosis, cell repair, and in particular inflammation. In this review, we offer a description of what many believe represents the primary regulatory cytokine, tumor necrosis factor (TNF)alpha and its role in toxicological processes. For over a decade it has been suspected that this molecule helps mediate the shock state induced by bacterial endotoxin and the wasting diathesis that typifies chronic diseases. Advances in molecular biology that have provided tools to modulate TNFalpha regulation and synthesis have allowed for the identification of additional roles for TNFalpha in homeostasis, cellular damage, and repair. This review provides a brief summary of our understanding of TNFalpha biology followed by a discussion of its role in toxicological responses. This is followed by specific examples of organ-specific and tissue-specific responses to chemical damage where TNFalpha has been implicated. The review concludes with a review of its implication in human risk assessment, particularly as it relates to genetic polymorphisms of TNFalpha expression and disease susceptibility.

Animals↗

PubMed1999

Autoimmunity and risk assessment.

Among the issues dealing with identifying potential adverse immunologic effects (i.e., suppression, hypersensitivity, or autoimmunity) associated with xenobiotic exposure, general agreement exists among the regulatory and pharmaceutical communities that predictive tests for autoimmunity are in most need of development in order to improve risk assessment. The estimation of risk (i.e., the probability of a deleterious effect resulting from exposure) involves both the qualitative evaluation of whether a hazard exists and the quantitative evaluation for determining an acceptable level of exposure in humans. Unless adequate human data are available, which is uncommon, this is based on animal studies. Although animal models exist to study autoimmune processes, these models do not readily lend themselves to interpretation in the risk assessment process due, for the most part, to the complexity of autoimmune disease(s), as they are multifactorial and exhibit genetic heterogeneity in humans. To improve the risk assessment process, researchers must develop and validate animal models that not only incorporate mechanistic information into the assessment process but also allow for consideration of potent genetic, physiologic, and environmental influences.

Animals↗

PubMed1998

Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms.

Hepatocytes, as well as nonparenchymal cells, secrete proinflammatory cytokines and chemokines that are involved in the pathology of many liver diseases. In particular, tumor necrosis factor-alpha (TNFalpha), as well as members of the CXC family of chemokines, including interleukin (IL)-8 in humans and macrophage inflammatory protein (MIP)-2 in rodents, have been implicated in both damage and repair processes associated with various hepatotoxins. In the liver, cytokine secretion is usually associated with nonparenchymal cells, particularly Kupffer cells. In the present studies, cytokine gene expression and secretion were investigated in hepatocytes treated with cadmium chloride (CdCl2) or vanadium pentoxide (V2O5). Using human Hep G2 cells and freshly isolated rodent hepatocytes, it was demonstrated that metals increase gene expression and secretion of CXC chemokines and TNFalpha. IL-8 and MIP-2 secretion induced either by the metals or H2O2 were inhibited by antioxidants such as tetramethyl-thiourea and N-acetyl-cysteine. In vitro neutralization experiments with TNFalpha and in vivo studies with TNFalpha receptor knockout mice indicated that the metals directly stimulate CXC chemokine secretion without the need for TNFalpha. Taken together these studies indicate that, in addition to other inflammatory mediators and acute phase proteins, cytokines and chemokines are produced by hepatocytes, which may participate in hepatotoxic responses. The events responsible for their expression involve cellular redox changes.

Animals↗

PubMed1998

Amelioration of virulent Babesia bovis infection in calves by administration of the nitric oxide synthase inhibitor aminoguanidine.

Calves undergoing initial infection with a virulent strain of the haemoprotozoan parasite Babesia bovis were treated with aminoguanidine (AG), an inhibitor of the inducible form of nitric oxide synthase (iNOS). The mean maximum parasitaemia of the AG treated calves was significantly lower than that of the control cattle. In addition, the febrile response and decrease in packed cell volume (PCV) observed during acute infection were significantly ameliorated in the AG treated cattle relative to the controls. However, AG had no effect on the multiplication of B. bovis in the microaerophilous stationary-phase (MASP) in-vitro culture system. These results provide evidence of a role for nitric oxide (NO) produced in response to acute infection in the pathology of bovine babesiosis.

Anemia↗

PubMed1998

Cytokine expression in hepatocytes: role of oxidant stress.

Inflammatory mediators, including cytokines and chemokines, are associated with the pathology of chronic liver disease. Interleukin-8 (IL-8) in humans and macrophage inflammatory protein-2 (MIP-2) in rodents, both members of the C-X-C family of chemokines, are particularly potent neutrophil attractants and have been implicated in chronic liver diseases. In the liver, cytokine secretion is usually associated with non-parenchymal cells, particularly Kupffer cells. In the present studies, chemokine gene expression and secretion were investigated in hepatocytes treated with various stimulators. Using human Hep G2 cells, it was demonstrated that, in contrast to lipopolysaccharides (LPS), both tumor necrosis factor-alpha (TNF-beta) and H2O2 are potent inducers of IL-8, presumably acting via protein kinase C (PKC)-dependent pathways. MIP-2 expression occurred in freshly isolated rat hepatocytes following treatment with TNF-alpha, LPS, and to a lesser degree, H2O2. Both IL-8 and MIP-2 secretion were inhibited, although to varying degrees, by such antioxidants as TMTU, DMSO, catalase, and N-acetylcysteine. Furthermore, in vitro TNF-alpha neutralization experiments and transfection of Hep G2 cells with an IL-8 construct confirmed that TNF-alpha and H2O2 directly stimulate IL-8 secretion. RT-PCR analyses indicated that chemokine secretion induced by these agents operates via increased gene expression. Furthermore, a variety of cytokine genes were found to be expressed by hepatocytes, including MCP-1, cytokine-induced neutrophil chemoattractant (CINC), and IL-6. Taken together, these studies indicate that hepatocytes respond to biologically relevant levels of common activators, including H2O2, to produce cytokines and chemokines that contribute to pathophysiologic and repair processes in the liver.

Animals↗

PubMed1998

Morbidity differences by occupational class among men in seven European countries: an application of the Erikson-Goldthorpe social class scheme.

BACKGROUND: This paper describes morbidity differences according to occupational class among men from France, Switzerland, (West) Germany, Great Britain, the Netherlands, Denmark, and Sweden. METHODS: Data were obtained from national health interview surveys or similar surveys between 1986 and 1992. Four morbidity indicators were included. For each country, individual-level data on occupation were recorded according to one standard occupational class scheme: the Erikson-Goldthorpe social class scheme. To describe the pattern of morbidity by occupational class, odds ratios (OR) were calculated for each class using the average of the population as a reference. The size of morbidity differences was summarized by the OR of two broad hierarchical classes. All OR were age-adjusted. RESULTS: For all countries, a lower than average prevalence of morbidity was found for higher and lower administrators and professionals as well as for routine nonmanual workers, whereas a higher than average prevalence was found for skilled and unskilled manual workers and agricultural workers. Self-employed men were in general healthier than the average population. The relative health of farmers differed between countries. The morbidity difference between manual workers and the class of administrators and professionals was approximately equally large in all countries. Consistently larger inequality estimates, with no or slightly overlapping confidence intervals, were only found for Sweden in comparison with Germany. CONCLUSIONS: Thanks to the use of a common social class scheme in each country, a high degree of comparability was achieved. The results suggest that morbidity differences according to occupational class among men are very similar between different European countries.

Adult↗

PubMed1998

Differences in self reported morbidity by educational level: a comparison of 11 western European countries.

STUDY OBJECTIVE: To assess whether there are variations between 11 Western European countries with respect to the size of differences in self reported morbidity between people with high and low educational levels. DESIGN AND METHODS: National representative data on morbidity by educational level were obtained from health interview surveys, level of living surveys or other similar surveys carried out between 1985 and 1993. Four morbidity indicators were included and a considerable effort was made to maximise the comparability of these indicators. A standardised scheme of educational levels was applied to each survey. The study included men and women aged 25 to 69 years. The size of morbidity differences was measured by means of the regression based Relative Index of Inequality. MAIN RESULTS: The size of inequalities in health was found to vary between countries. In general, there was a tendency for inequalities to be relatively large in Sweden, Norway, and Denmark and to be relatively small in Spain, Switzerland, and West Germany. Intermediate positions were observed for Finland, Great Britain, France, and Italy. The position of the Netherlands strongly varied according to sex: relatively large inequalities were found for men whereas relatively small inequalities were found for women. The relative position of some countries, for example, West Germany, varied according to the morbidity indicator. CONCLUSIONS: Because of a number of unresolved problems with the precision and the international comparability of the data, the margins of uncertainty for the inequality estimates are somewhat wide. However, these problems are unlikely to explain the overall pattern. It is remarkable that health inequalities are not necessarily smaller in countries with more egalitarian policies such as the Netherlands and the Scandinavian countries. Possible explanations are discussed.

Adult↗

PubMed1998

Modafinil: a novel stimulant for the treatment of narcolepsy.

Excessive daytime sleepiness (EDS) is a common and debilitating symptom of narcolepsy and other sleep disorders. Modafinil is a novel stimulant which effectively treats EDS, yet lacks many of the undesirable side-effects commonly encountered with currently available compounds. The specific mode of action of modafinil is not well understood, but it may promote sleep by indirectly influencing adrenergic or GABAergic neurotransmission. Modafinil-induced wakefulness is not associated with rebound hypersomnolence or the potential for abuse as is often encountered with other stimulants such as amphetamines. At typical therapeutic doses, modafinil may produce dry mouth but generally has a low incidence of minor side-effects. Many preclinical and clinical studies have demonstrated the effectiveness of modafinil in promoting wakefulness and vigilance in normal subjects and in those with EDS. Modafinil significantly improves the EDS of narcolepsy and also may improve the EDS of idiopathic hypersomnia and obstructive sleep apnoea. Modafinil's low prevalence of side-effects, minimal potential for abuse, and lack of rebound hypersomnia indicate that it has potential to become a widely prescribed drug for the treatment of narcolepsy.

Journal Article↗

PubMed1997

Efficacy of laser-assisted uvulopalatoplasty.

BACKGROUND AND OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is being used increasingly as a surgical treatment for snoring and obstructive sleep apnea (OSA). There is limited evidence for the success of LAUP in eliminating OSA. This study assesses the efficacy of LAUP in eliminating snoring and OSA and addresses which patients may be the best candidates for LAUP treatment. STUDY DESIGN/MATERIALS AND METHODS: From January 1994 to January 1996, 297 patients were evaluated for snoring, with 190 (64%) exhibiting some degree of OSA documented by a PSG: 41/ 190 (22%) mild OSA; 33/190 (17%) moderate OSA; 85/190 (45%) severe OSA; 31/190 (16%) severity unknown. Ninety patients (90/ 297) have undergone LAUP treatment: 58/90 (64%) with OSA and 32/90 (36%) with snoring only. RESULTS: Our results indicate a significant reduction of snoring in patients without OSA, but diminishing success in patients with increasing degrees of OSA. Additionally, LAUP was not efficacious in treating OSA: pre-op respiratory disturbance index (RDI) of 10.8 vs. post-op RDI of 19.5 for mild OSA (P = 0.14); pre-op RDI of 22.9 vs. post-op RDI of 25.4 for moderate OSA (P = 0.43); pre-op RDI of 56.8 vs. post-op RDI of 46.3 (P < 0.05), which is statistically but not clinically significant (i.e., RDI remained in the severe range). CONCLUSION: We conclude that LAUP is an effective treatment for nonapneic snoring, but does not provide sufficient resolution of OSA, and based on our results, LAUP should be considered as an adjunctive therapy rather than a sole treatment for OSA in most cases.

Adult↗

PubMed1995

Isolation and characterization of a trypsin-like enzyme from the buffalo fly, Haematobia irritans exigua.

The incorporation of soybean trypsin inhibitor (SBTI) into the diet of the buffalo fly, Haematobia irritans exigua (De Meijere), results in increased mortality and reduced fecundity. A trypsin-like enzyme which binds to SBTI was isolated by affinity chromatography on a Sepharose-SBTI column followed by ion-exchange chromatography. The enzyme was inhibited by benzamidine, phenylmethylsulfonyl fluoride, ovomucoid, leupeptin and alpha-2 macroglobulin. The enzyme was not inhibited by EDTA or p-chloromecuribenzoic acid and had a broad pH optimum of pH 7-9. Vaccination of sheep produced antibodies specific for the trypsin-like enzyme which inhibited enzyme activity in vitro but did not affect the survival of flies maintained in in vitro culture.

Animals↗

PubMed1993

Treatment of obsessive-compulsive disorder by psychosurgery.

We report a longitudinal study of 26 patients with medically intractable obsessive-compulsive disorder (OCD) who were treated with psychosurgery and had a comprehensive follow-up for a mean 10 years. Seventeen patients had combined orbitomedial and cingulate lesions, 6 cingulate lesions only and 3 orbitomedial lesions only. Eighteen patients were interviewed personally and lesions verified on magnetic resonance imaging scans in fourteen. On a 6-point global rating scale, 10 (38%) patients had obvious improvement, another 6 (23%) showed mild improvement of doubtful clinical value, and the remaining 10 showed either no change (n = 6; 23%) or were judged to be worse (n = 4; 15%). Both obsessive and compulsive symptoms improved, and this change was independent of the changes in anxiety and depression scores. No significant predictors of improvement were identified. Patients with cingulate lesions only fared worse. Eight patients who had a second operation did not show much improvement. A comparison of a subgroup of patients with 10 matched nonsurgical OCD controls supported the contention that the improvement in OCD was attributable to the psychosurgery. Important adverse effects in the stereotactic surgery group (n = 20) were epilepsy (1 patient) and personality change (2 patients). The psychosurgery group performed relatively poorly on the Wisconsin Card Sort Test but did not show any deterioration in Wechsler Intelligence and Memory scores.

Adult↗