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Biomedical subjects

E Atkinson

Publications and source records attributed to E Atkinson.

At least 19 recordsLinked to original sources
PubMed2001

Genetic variation in the transforming growth factor beta1 gene in multiple sclerosis.

Transforming growth factor beta1 (TGFbeta1) is a Th2 cytokine encoded on chromosome 19q13, a region possibly linked to multiple sclerosis (MS). TGFbeta1 exerts favorable effects on experimental allergic encephalomyelitis. We performed a comprehensive search for genetic variants in this gene in 122 population-based sporadic cases of MS. We detected six variants, including three missense variants. We tested for association of the variants with susceptibility and course of MS and for linkage and transmission disequilibrium in a family series consisting of 395 samples in 59 pedigrees. Genetic variation in TGFB1 does not appear to contribute in a major way to susceptibility to MS.

Adult↗
PubMed1999

Genetic variants in the tumor necrosis factor receptor 1 gene in patients with MS.

We scanned for all genetic variants in functionally important regions of the tumor necrosis factor receptor 1 gene (TNF-R1) in 100 to 111 MS patients from Olmsted County, MN, and analyzed selected variants for an association with disease course and severity. Ten genetic variants were uncovered. Only one variant, a silent substitution, was found in coding sequence. One intronic variant may generate a novel splice-junction sequence. We did not find an association between either this intronic variant or another common promoter variant and the course or severity of MS.

Chromosome Mapping↗
PubMed1999

Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40-CD40 ligand signaling in vitro and in vivo.

Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques (n = 7) express stromelysin-3 in situ, whereas fatty streaks (n = 5) and normal arterial specimens (n = 5) contain little or no stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-gamma, or tumor necrosis factor alpha did not augment stromelysin-3 in vascular wall cells. However, T cell-derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of stromelysin-3. In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40-CD40L signaling pathway in low density lipoprotein receptor-deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase stromelysin-3 in human atherosclerotic lesions and implicate CD40-CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions.

Animals↗
PubMed1999

T lymphocytes induce endothelial cell matrix metalloproteinase expression by a CD40L-dependent mechanism: implications for tubule formation.

Neovascularization frequently accompanies chronic immune responses characterized by T cell infiltration and activation. Angiogenesis requires endothelial cells (ECs) to penetrate extracellular matrix, a process that involves matrix metalloproteinases (MMPs). We report here that activated human T cells mediate contact-dependent expression of MMPs in ECs through CD40/CD40 ligand signaling. Ligation of CD40 on ECs induced de novo expression of gelatinase B (MMP-9), increased interstitial collagenase (MMP-1) and stromelysin (MMP-3), and activated gelatinase A (MMP-2). Recombinant human CD40L induced expression of MMPs by human vascular ECs to a greater extent than did maximally effective concentrations of interleukin-1beta or tumor necrosis factor-alpha. Moreover, activation of human vascular ECs through CD40 induced tube formation in a three-dimensional fibrin matrix gel assay, an effect antagonized by a MMP inhibitor. These results demonstrated that activation of ECs by interaction with T cells induced synthesis and release of MMPs and promoted an angiogenic function of ECs via CD40L-CD40 signaling. As vascular cells at the sites of chronic inflammation, such as atherosclerotic plaques, express CD40 and its ligand, our findings suggest that ligation of CD40 on ECs can mediate aspects of vascular remodeling and neovessel formation during atherogenesis and other chronic immune reactions.

CD40 Antigens↗
PubMed1999

Distal mucocolpos and proximal hematocolpos secondary to concurrent imperforate hymen and transverse vaginal septum.

A 12-year-old girl had cruciate incision of imperforate hymen draining a large mucocolpos. Her symptoms did not abate thereafter, and 3 months later a transverse vaginal septum was diagnosed. This was perforated and dilated under ultrasound (US) guidance draining a large hematocolpos. Results of examination under anesthesia after 3 months was satisfactory, and she has had normal periods in follow-up for 9 months. Imperforate hymen and transverse vaginal septum are known causes of mucocolpos and hematocolpos. However, the concurrent occurrence of the two abnormalities is unique.

Child, Preschool↗
PubMed1999

Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ.

Several studies have shown an association between high nuclear grade or necrosis of ductal carcinoma in situ (DCIS) lesions and the risk of local disease recurrence in patients with DCIS treated surgically with less than mastectomy. Although criteria for separating low from high nuclear grade lesions have been published, no information exists regarding interobserver reproducibility (IR). To assess IR in the classification of DCIS, six surgical pathologists from four institutions used the Lagios grading system to grade 125 DCIS lesions. Before meeting to evaluate the cases, a training set of 12 glass slides, including cases chosen to present conflicting cues for classification, was mailed to the participants with a written criteria summary. This was followed by a working session in which criteria were reviewed and agreed on. The pathologists then graded the lesions independently. The area of interest was marked on each slide before grading. After initial grading, the pathologists met again to resolve discrepant lesion classifications. A complete agreement among raters was achieved in 43 (35%) cases, with five of six raters agreeing in another 45 (36%) cases. In no case did two raters differ by more than one grade. The pairwise kappa agreement values ranged from fair to substantial (0.30 to 0.61). Generalized kappa value indicated moderate agreement (0.46, standard error = 0.02). Kappa statistics for the distinction between grades 1 and 2 and 2 and 3 were 0.29 and 0.48, respectively, (standard error = 0.02). Only one of the six raters differed significantly in scoring. With adherence to specific criteria, IR in the classification of DCIS cases can be obtained in most cases. Although these pathologists made a few grading system modifications, further refinements are needed, especially if grading will influence future therapy.

Breast Neoplasms↗
PubMed1998

Reduction of atherosclerosis in mice by inhibition of CD40 signalling.

Increasing amounts of evidence support the involvement of inflammation and immunity in atherogenesis, but mediators of communication between the major cell types in atherosclerotic plaques are poorly defined. Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand CD40L (also known as CD154 or gp39). The interaction of CD40 with CD40L figures prominently in both humoral and cell-mediated immune responses. CD40L-positive T cells accumulate in atheroma, and, by virtue of their early appearance, persistence and localization at sites of lesion growth and complication, activated T cells may coordinate important aspects of atherogenesis. Interruption of CD40L-CD40 signalling by administration of an anti-CD40L antibody limits experimental autoimmune diseases such as collagen-induced arthritis, lupus nephritis, acute or chronic graft-versus-host disease, multiple sclerosis and thyroiditis. Ligation of CD40 on atheroma-associated cells in vitro activates functions related to atherogenesis, including induction of proinflammatory cytokines, matrix metalloproteinases, adhesion molecules and tissue factor. However, the role of CD40 signalling in atherogenesis in vivo remains unknown. Here we determine whether interruption of CD40 signalling influences atherogenesis in vivo in hyperlipidaemic mice. Treatment with antibody against mouse CD40L limited atherosclerosis in mice lacking the receptor for low-density lipoprotein that had been fed a high-cholesterol diet for 12 weeks. This antibody reduces the size of aortic atherosclerotic lesions by 59% and their lipid content by 79%. Furthermore, atheroma of mice treated with anti-CD40L antibody contained significantly fewer macrophages (64%) and T lymphocytes (70%), and exhibited decreased expression of vascular cell adhesion molecule-1. These data support the involvement of inflammatory pathways in atherosclerosis and indicate a role for CD40 signalling during atherogenesis in hyperlipidaemic mice.

Animals↗
PubMed1997

Relative contributions of incidence and survival to increasing prevalence of adult-onset diabetes mellitus: a population-based study.

This population-based retrospective study investigates temporal trends in adult-onset diabetes mellitus prevalence, incidence, and survival. The complete community-based medical records, including laboratory results, of all Rochester, Minnesota, residents with a clinical diagnosis of diabetes or diabetes-like condition were reviewed to identify incidence cases aged 30 years or more from 1945 to 1989 (n = 1,847) and prevalence cases aged 45 years or more on January 1, 1970 (n = 465), January 1, 1980 (n = 689), or January 1, 1990 (n = 973). Glucose values and case definitions were standardized throughout. Observed 10-year survival for 1970 and 1980 prevalence cases was compared with that expected for Minnesota white populations in 1970 and 1980, respectively. Age-adjusted prevalence rose 65% for men and 37% for women between 1970 and 1990. There were marked differences among prevalence groups in treatment type, the proportion diagnosed using glucose tolerance tests, and the proportion categorized as obese. Relative survival for 1980 prevalence cases was not greater than that for 1970 prevalence cases. Age-adjusted incidence rates rose 47% for men and 26% for women between 1960 and 1965 and 1985 and 1989. These findings emphasize the need for heightened surveillance and intervention to reduce the burden of illness from adult-onset diabetes mellitus in the population.

Age Distribution↗
PubMed1997

Identification of a serpin specifically expressed in multipotent and bipotent hematopoietic progenitor cells and in activated T cells.

We have identified a gene that has a high level of mRNA expression in undifferentiated, multipotential hematopoietic cells (FDCP-Mix) and that downregulates both transcript and protein, as these cells are induced to differentiate into mature myeloid cells. Sequence analysis of this gene has identified it as a serine protease inhibitor EB22/3 (serpin 2A). Constitutive expression of serpin 2A in FDCP-Mix cells was associated with an increase in the clonogenic potential of the cells and with a delay in the appearance of fully mature cells in cultures undergoing granulocyte macrophage differentiation when compared with control cells. Serpin 2A was also found to be expressed in bone marrow-derived bipotent granulocyte macrophage progenitor cells (GM-colony forming cell [CFC]), but not in erythrocyte progenitor cells from day 15 fetal liver. Expression of serpin 2A also showed a marked up regulation during the activation of cytotoxic suppressor CD8+ T cells, with a clear lag between the appearance of transcript and detection of protein.

Amino Acid Sequence↗
PubMed1995

Sleep disruption in young children. The influence of temperament on the sleep patterns of pre-school children.

Sleep problems are a common concern of parents with toddlers. Various reasons have been put forward as to the possible causes and maintenance of sleep disruption. These have included neurophysical differences in the child, perinatal differences such as a long labour and depression and anxiety in the parents themselves resulting in adverse effects on the child's sleep patterns. However, recent research has indicated that a child's temperamental style may be a possible causal factor as to whether the child will present its parents with a sleep problem. This study, therefore, sets out to investigate the importance of temperament as a predictor of whether children may or may not have sleep problems. Environmental factors are controlled as far as possible by selecting toddlers with and without sleep problems from very similar environments. Case studies are also introduced to further illuminate other possible associated factors such as parental handling. The results from this study found significant differences in the temperament profiles of children with and without sleep problems. Children with reported sleep problems were more likely to obtain a 'intermediate high to difficult' profile. Various findings from a group of toddlers with and without sleep problems are discussed in this paper together with implications of the findings and recommendations for further research.

Behavior Therapy↗
PubMed1992

Residential and community treatment services utilized by a sample of youth with severe emotional disturbances.

Analyzed case records to determine the costs and service usage patterns for a group of 25 youth randomly selected from the case load of a regional mental health agency. Study participants had extensive histories of publicly supported psychiatric hospitalizations. An average of 36.2 contacts per youth (905 total contacts) with human services providers were documented. Approximately 2 out of every 5 contacts resulted in out-of-home placements. The estimated cost of providing services to the 25 youth exceeded 3 million dollars. The types and costs of treatment services provided to study participants are discussed.

Adolescent↗
PubMed1990

Uterine perforation during second-trimester abortion by cervical dilation and instrumental extraction: a review of 15 cases.

Review of the records of 15 women who had uterine perforations at the time of second-trimester abortion by dilation and evacuation showed that unexpected pain (but not excessive bleeding) was the most prominent sign. All patients required laparotomy, but in no case was laparotomy necessary as an emergency procedure. Laparoscopy was not helpful. Two-thirds had bowel injuries and two required hysterectomy. Errors in estimating gestational duration, inadequate cervical dilation, and failure to use sonography characterized these complicated cases.

Abortion, Induced↗
PubMed1987

Solvent influence on model oxidations of alpha-tocopherol.

(+/-)-alpha-Tocopherol has been oxidised with t-butyl hydroperoxide in chloroform in order to simulate in vivo oxidations due to lipid hydroperoxides. t-Butyl hydroperoxide proved to be a weak oxidant and failed to oxidise alpha-tocopherol in 3 h at 60 degrees C. Inclusion of a small amount of ethanol in the reaction mixture brought about immediate oxidation and the formation of a new product, 5-ethoxymethyl-7,8-dimethyltocol in addition to the spiro dimer and spiro trimer of alpha-tocopherol, alpha-tocopherylquinone and 5-formyl-7,8-dimethyltocol. Formation of 5-ethoxymethyl-7,8-dimethyltocol increased with increasing concentrations of ethanol, up to a maximum of 59% at 20% ethanol. Further increase in ethanol concentration brought about a decrease in the oxidation of alpha-tocopherol and in the formation of 5-ethoxymethyl-7,8-dimethyltocol. Oxidation of the tocopherol model compound 2,2,5,7,8-pentamethyl-6-hydroxychroman under similar conditions produced the analogous product, 5-ethoxymethyl-2,2,7,8-tetramethyl-6-hydroxychroman together with 5-formyl-2,2,7,8-tetramethyl-6-hydroxychroman and 2-(3'-hydroxy-3'-methylbutyl)-3,5,6-trimethylbenzo-1,4-quinone.

Catalysis↗
PubMed1987

Modulation of experimental retinal vasculitis using dexamethasone, cyclosporin A, and prazosin.

The effects of dexamethasone, cyclosporin A and prazosin were investigated in an animal model of retinal vasculitis. Both dexamethasone and cyclosporin A reduced the clinical and pathological signs of disease when given from the day of disease onset. Prazosin, an alpha 1 adrenergic antagonist, was given during the period of disease induction and blocked fluorescein leakage from actively inflamed retinal vessels, but had little effect on the clinical and pathological signs of disease. This study demonstrates the feasibility of using this animal model for therapeutic trials of anti-inflammatory agents in retinal vasculitis. The effect of prazosin on reducing vascular leakage from retinal vessels has implications for the treatment of inflammatory macula oedema in human disease.

Animals↗