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M R Wilson

Publications and source records attributed to M R Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Polycyclic aromatic hydrocarbons with bay-like regions inhibited gap junctional intercellular communication and stimulated MAPK activity.

Many polycyclic aromatic hydrocarbons (PAHs) are known carcinogens. A considerable amount of research has been devoted to predicting the genotoxic, tumor-initiating potential of PAHs based on chemical structure. However, information on the correlation of structure with the non-genetoxic, epigenetic events of tumor promotion is sparse. PAHs containing a bay or bay-like region were shown to be potent inhibitors of gap-junctional intercellular communication (GJIC), an epigenetic event involved in the removal of an initiated cell from growth suppression. We tested the epigenetic toxicity of PAHs containing bay-like regions by comparing the effects of methylated vs. chlorinated isomers of anthracene on the temporal activation of mitogen-activated protein kinase (MAPK) and the regulation of GJIC. Specifically, we used anthracene, 1-methylanthracene, 2-methylanthracene, 9-methylanthracene, 9,10-dimethylanthracene, 1-chloroanthracene, 2-chloroanthracene, and 9-chloroanthracene. We determined the effect of these compounds on GJIC and on the activation of extracellular receptor kinase (ERK 1 and 2), a MAPK, in F344 rat liver epithelial cells. Results showed that bay or bay-like regions, formed by either chlorine or a methyl group, reversibly inhibited GJIC at the same doses, time, and time of recovery, whereas the linear-planar isomers had no effect on GJIC. Similarly, the GJIC-inhibitory isomers also induced the phosphorylation of ERK 1 and ERK 2, while the non-inhibitory isomers had no effect on the activation of these MAPKs. MAPK activation occurred 10-20 min after the inhibition of GJIC, which indicates that MAPK is not involved in the initial regulation of GJIC; instead altered GJIC may be affecting MAPK activation. The present study revealed that there are structural determinants of PAHs, which clearly affect epigenetic events known to be involved in the non-genetoxic steps of tumor promotion. These events are the release of a cell from growth suppression involving the reduction of GJIC, followed by the activation of intracellular mitogenic events.

Animals↗
PubMed1999

Retrieval analyses of implanted biomaterials: light microscopic and scanning electron microscopic analyses of implants retrieved from humans.

We report analyses obtained from 135 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation--Medical College of Georgia Implant Retrieval Center. The undecalcified samples were embedded in polymethyl-methacrylate and examined with scanning electron microscopy and with routine light via polarized or Nomarski microscopy. Cases included both orthopedic and dental implants as well as entire mandibles obtained at autopsy. Significant numbers of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As has been observed in animal studies, an interdigitating canaliculi network provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Significant numbers of osseointegrated fractured hydroxyapatite-coated dental implants demonstrated the adequate serviceability of these implants prior to biomaterial fracture. In contrast, the hydroxyapatite coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. Caution is advised for the use of hydroxyapatite-coated acetabular implants. This study therefore underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

Aged↗
PubMed1999

Central nervous system and plasma lipid profiles associated with carteolol and timolol in postmenopausal black women.

PURPOSE: Among ocular hypotensive agents, intrinsic sympathomimetic activity (ISA) is unique to carteolol hydrochloride. This study was conducted to evaluate the central nervous system (CNS) and plasma lipid profiles associated with timolol maleate and carteolol hydrochloride in postmenopausal black women with primary open-angle glaucoma (POAG) or ocular hypertension. METHODS: One hundred subjects met the inclusion and exclusion criteria for this randomized, double-masked, multicenter, parallel-group study. After completion of informed consent and complete ophthalmic examination, eligible patients entered a washout period, during which no topical ophthalmic medications were used. Blood samples were obtained for hematology and blood chemistry evaluations. Vital signs, ocular symptoms, Symptom Checklist-90-R (SCL-90-R) evaluation, intraocular pressure (IOP) measurements, and slit-lamp examinations were performed before randomization to treatment with either topical carteolol hydrochloride 1.0% or topical timolol maleate 0.5%. Patients received active medications twice daily and were monitored at 4 weeks and 12 weeks. At the conclusion of treatment, vital signs, ocular symptoms, SCL-90-R evaluation, IOP, slit-lamp examinations, and blood samples were obtained. RESULTS: Compared with baseline, high-density lipoprotein (HDL) cholesterol was significantly decreased (worsened) in the timolol group but did not change significantly in the carteolol group. The between-group difference was statistically significant. Total cholesterol to HDL ratio significantly increased (worsened) in the timolol group compared with baseline but did not change in the carteolol group. The difference between groups was statistically significant. No significant differences were observed between groups in SCL-90-R results for either somatization or depression. CONCLUSIONS: These results suggest that topical carteolol hydrochloride may have a more favorable blood lipid profile than topical timolol maleate in postmenopausal black women with POAG or ocular hypertension. Carteolol and timolol appear to have similar CNS side effect profiles.

Adrenergic beta-Antagonists↗
PubMed1998

Impaired glucose-stimulated insulin release in islets from adult rats malnourished during foetal-neonatal life.

Poor foetal and neonatal nutrition may impair normal pancreatic beta-cell development and predispose to diabetes in later life. We investigate here the nature of the pancreatic beta-cell dysfunction in sucrose-fed adult offspring malnourished during the foetal-neonatal period and examine glucose metabolism and the generation of signals involved in the secretory mechanism. In islets from sucrose-fed previously malnourished rats, rates of glucose utilisation (production of 3H2O) and oxidation (production of 14CO2), at 2, 6 and 10 mM glucose, were not lower than those of controls. ATP concentrations in islets from previously malnourished rats fed sucrose at 2 and 10 mM glucose were similar to those of controls. Glucose-stimulated insulin release was impaired (by 49-55%) in islets from these animals as was the response to keto-isocaproate (by 70%) and tolbutamide (by 70%). Under conditions in which ATP-sensitive K+ channels were clamped open (40 mM K+ and diazoxide), glucose-stimulated insulin release in islets from previously malnourished rats fed sucrose was reduced. These findings show that defects in insulin secretion in islets isolated from previously malnourished animals are located in both ATP-sensitive K+ channel dependent and independent pathways. They do not involve alterations in the early steps of glucose handling in the beta-cell, including glucose metabolism and ATP generation.

Adenine Nucleotides↗
PubMed1998

Characterization of Oct2 from the channel catfish: functional preference for a variant octamer motif.

The Ig heavy chain enhancer of the channel catfish (Ictalurus punctatus) has an unusual position and structure, being found in the 3' region of the mu gene and containing eight functional octamer motifs of consensus (ATGCAAAT) and variant sequences. The presence of multiple octamer motifs suggests that an Oct2 homologue may play an important role in driving expression of the Ig heavy chain locus in a teleost fish. To test this hypothesis, two catfish Oct2 cDNAs (alpha and beta) were cloned by screening a catfish B cell cDNA library. Catfish Oct2 alpha and beta isoforms are derived by alternative RNA splicing; as determined by Southern analysis, Oct2 is a single copy gene. In comparisons with mammalian Oct2, the catfish Oct2 isoforms show high sequence conservation in their N-terminal regions and POU domains, but extensive divergence in their C-terminal regions. Catfish Oct2 a and beta are tissue restricted, bind both consensus and variant octamer motifs, and activate transcription in both catfish and murine cells. In contrast, mouse Oct2 activated transcription in mouse but not catfish cells. Catfish Oct2 beta is a more potent transcriptional activator than Oct2 alpha. In transient expression assays, catfish Oct2 beta showed a marked preference for the octamer variant, ATGtAAAT, which occurs twice in the catfish enhancer. Mouse Oct2 also showed increased activity with the variant octamer when tested in mouse B cells. Gel-shift analysis competition assays indicated that catfish Oct2 binds the consensus octamer motif with an apparently higher affinity than it does the variant motif.

Alternative Splicing↗
PubMed1998

Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells: a potential anti-atherogenic function?

Apolipoprotein J (apo J) is a secreted glycoprotein of which the exact function remains a matter for speculation. Apo J has been implicated in such diverse processes as sperm maturation, regulation of complement activation, programmed cell death, tissue remodelling and lipid transport. In this study a possible role for apo J in lipid transport was explored. Mouse peritoneal macrophages were incubated with acetylated low-density lipoprotein (AcLDL) to produce foam cells containing cholesterol and cholesteryl esters. Incubation of the foam cells with physiological concentrations of purified apo J led to a dose-dependent export of cholesterol. The appearance of cholesterol in the medium was associated predominantly with a decline in intracellular cholesteryl esters rather than intracellular free cholesterol. The kinetics of cholesterol release to apo J were similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also shown to induce phospholipid efflux from cells, whereas the cholesterol exported to the medium was associated with the apo J. Studies using foam cells from apo E-null mice showed that the cholesterol exported to the medium was independent of apo E production by the cells. These results present the first evidence that apo J can promote cholesterol efflux from foam cells and indicates that it might have a function in cellular cholesterol homoeostasis in both normal and pathological situations.

Animals↗
PubMed1998

The Glaucoma Symptom Scale. A brief index of glaucoma-specific symptoms.

OBJECTIVE: To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). DESIGN: Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. PATIENTS: A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. MAIN OUTCOME MEASURES: Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. RESULTS: The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between persons with and without glaucoma. Additionally, tests of association with clinical markers of glaucoma severity support the clinical validity of the measure and tests of association with established vision-targeted measures provide evidence of construct validity. CONCLUSION: The simplicity, brevity, and psychometric properties of the GSS support its use in clinical practice and research to quantify symptoms in patients with glaucoma and to assist in investigations concerning the effect of glaucoma and treatments.

Cross-Sectional Studies↗
PubMed1998

Rapid mitochondrial DNA typing using restriction enzyme digestion of polymerase chain reaction amplicons followed by capillary electrophoresis separation with laser-induced fluorescence detection.

The polymorphic control region of mitochondrial DNA (mtDNA) is becoming more commonly used in forensic applications to differentiate among individuals in a population. Two hypervariable regions (HV1 and HV2) are often sequenced following amplification of the mtDNA via the polymerase chain reaction (PCR). More rapid screening assays would reduce both the effort and the expense of comparing two samples. A methodology has been developed that first uses restriction endonuclease digestion of the PCR-amplified mtDNA using RsaI and MnlI and then capillary electrophoresis (CE) to separate and size the PCR-RFLP fragments. This rapid procedure offers an alternative method for screening of polymorphisms in amplified mtDNA samples. In addition, the presence of a T-->C transition at position 16189, which gives rise to the so-called "C-stretch" in HV1, may be predicted from the presence of nonspecific PCR products in the CE results.

Computer Simulation↗
PubMed1998

Lower fat intake as a predictor of initial and sustained weight loss in obese subjects consuming an otherwise ad libitum diet.

OBJECTIVE: To determine what predicts initial and sustained weight loss in subjects consuming a reduced-fat diet ad libitum and the relationship between achieved level of fat intake and weight loss. DESIGN: Placebo arm of a randomized, controlled trial of a weight-loss drug (dexfenfluramine) in the context of an ad libitum, reduced-fat diet. SUBJECTS: Thirty-nine subjects (initial mean body mass index +/- standard deviation = 34.9 +/- 3.4; body mass index is calculated as kg/m2) from the placebo group who completed the 9-month study. INTERVENTION: Dietary assessment and education (month 0) followed by monthly meetings during the single intervention of reducing fat intake (months 1 through 6); one follow-up at 9 months. MAIN OUTCOME MEASURES: Initial weight loss (first 3 months) and sustained weight loss (over 9-month period). STATISTICS: Dietary intake, body size, exercise levels, age, and gender were included in multiple regression linear models of initial and sustained weight loss if they were significant independent predictors. RESULTS: Greater initial weight loss was associated with a greater decrease in fat intake and a lower achieved fat intake at 3 months. Greater sustained weight loss was associated with a lower achieved fat intake, a higher baseline waist circumference, and higher moderate-intensity exercise levels (months 3 and 6). Weight loss occurred in all subjects who reported a fat intake of 40 g/day or less. APPLICATIONS: The obese persons most likely to achieve and sustain weight loss on an ad libitum, reduced-fat diet are those who can substantially reduce fat intake, those with high initial levels of abdominal fat, and those who undertake regular moderate-intensity exercise. A target of less than 40 g fat per day might be an appropriate goal to ensure weight loss, but dietary underreporting and the difficulty of sustaining very-low-fat intakes need to be considered.

Adult↗
PubMed1998

Mitogen and growth factor-induced activation of a STAT-like molecule in channel catfish lymphoid cells.

This article describes the identification of a putative STAT molecule in the channel catfish (Ictalurus punctatus), the first report of such a molecule in a 'lower' vertebrate. A monoclonal antibody against human STAT6 recognizes an approximately 100 kDa molecule that becomes activated and translocates to the nucleus upon both growth factor and mitogen stimulation of catfish leukocytes. This presumed catfish STAT binds the mammalian interferon-gamma activation site, a known motif of mammalian STAT binding, as shown by electromobility shift assays. Purification of the proteins present in these DNA complexes confirms that the catfish reactive molecule binds to the interferon-gamma activation site sequence. These results suggest that STAT molecules have been highly conserved in vertebrate evolution.

Animals↗
PubMed1998

T-cell receptors in channel catfish: structure and expression of TCR alpha and beta genes.

Herein are reported full length cDNA sequences for TCR alpha- and beta-chains of the channel catfish. Included are sequences belonging to four Valpha and six Vbeta families which share hallmarks in common with the Valpha and Vbeta genes of other species. Similar to the situation in other vertebrates, the catfish Calpha and Cbeta sequences exhibit distinct immunoglobulin, connecting peptide, transmembrane and cytoplasmic domains. However, the catfish TCR Calpha and Cbeta regions are shorter than those of mammals and the catfish Cbeta chain lacks a cysteine in its connecting peptide region. Two different catfish Cbeta cDNA sequences were identified, suggesting the existence of either two Cbeta loci or allotypes. Based on Southern blot analyses, each of the catfish TCR gene loci appear to be arranged in a translocon (as opposed to multicluster) organization with multiple V elements and a single or few copies of C region DNA. At the deduced amino acid level, the catfish Cbeta sequence exhibits 42% identity with the Cbeta of Atlantic salmon, 41% identity with the Cbeta of rainbow trout and 26% identity with Cbeta of the horned shark. The catfish Calpha amino acid sequence exhibits 44 and 29% identity with Calpha of the rainbow trout and southern pufferfish, respectively. TCRalpha and beta messages are selectively expressed and rearranged in a catfish clonal cell line that appears to be of the T lineage. This TCR alpha/beta expressing clonal lymphocyte line, designated 28S.1, has T-cell like function in that it constitutively produces a supernatant factor(s) with growth promoting activity. These findings should facilitate functional studies of fish TCRs and T cells in ways not previously possible with other 'lower' vertebrate models.

Amino Acid Sequence↗
PubMed1998

Functional status and well-being in patients with glaucoma as measured by the Medical Outcomes Study Short Form-36 questionnaire.

PURPOSE: This study aimed to determine whether patients with glaucoma have different functional status and well-being than patients without glaucoma. DESIGN: Prospective case-control study. PARTICIPANTS: The study population was recruited from 2 university-based glaucoma clinical practices and a university-based general ophthalmology clinic and consisted of 121 patients with open-angle glaucoma, 42 with diagnosis of glaucoma suspect, and 135 with no chronic ocular conditions except cataract. INTERVENTION: Administration of Medical Outcomes Study 36-item short-form survey (SF-36) was performed. Demographic information, medical history, and responses to the SF-36 questionnaire were elicited by an interviewer. Medical record review was performed to obtain clinical examination data and to substantiate the medical and demographic data obtained by the interviewer. MAIN OUTCOME MEASURES: The SF-36 scores by diagnostic group, demographic characteristics, and medical history were examined. Secondary outcome measures were SF-36 scores in patients with glaucoma by visual field impairment and glaucoma medication use. RESULTS: Patients with glaucoma consistently had lower scores, control subjects had higher scores, and glaucoma suspects had scores intermediate between the two groups. After adjusting for the possible influence of all the other covariate factors, glaucoma was found to be a strong predictor of lower SF-36 scores. CONCLUSION: Patients with glaucoma have lower scores, indicating less-functional status, than patients without glaucoma as tested by the SF-36 survey questionnaire.

Adult↗
PubMed1998

Demographic and clinical characteristics of patients with diabetes presenting to an urban public hospital ophthalmology clinic.

OBJECTIVE: This study aims to describe the clinical and sociodemographic characteristics of patients with diabetes who are newly presenting to an inner city public hospital eye clinic. This study also aims to determine the prevalence and severity of ocular morbidity in this population at time presentation and to assess the adequacy of the ophthalmic surveillance to which this population was exposed before presentation. DESIGN: A clinic-based, cross-sectional study. PARTICIPANTS: A total of 118 consecutive patients with diabetes participated. METHOD: During a 2-month interval, all patients with diabetes newly presenting to the Los Angeles County King-Drew Medical Center eye clinic were recruited who were at risk for diabetic eye complications according to American Diabetes Association criteria. Each patient underwent a standardized interviewer-administered questionnaire and a comprehensive ophthalmic examination. RESULTS: Of the 118 patients, 65 (55%) were Hispanic and 51 (43%) were African American. Forty-six percent had a grade school education or less, 91% were unemployed, and 64% had no health insurance. Type two diabetes was predominant (91%), including 24 (22%) of new onset. Thirty-six patients with diabetes (31%) reported duration of diabetes greater than 10 years at time of presentation. At time of presentation, 62% had clinically apparent ophthalmic disease, whereas 40% had advanced ocular disease, including 6.8% of the sample that were legally blind. Sixty-nine patients (58.5%) reported never having had a dilated fundus examination, whereas 31 (63%) of the 49 patients reporting a previous dilated examination were last examined more than 2 years before presentation. Timing of ophthalmic examination was classified as appropriate for 38 patients (32%), marginal for 20 patients (17%), and inappropriate for 60 patients (51%). CONCLUSION: In the setting of an inner city county hospital eye clinic, where the patient population is predominately minority and of low socioeconomic status, ophthalmic surveillance of high-risk patients with diabetes is inadequate and advanced disease often is present at initial presentation. Strategies must be developed to increase the routine use of eye services within this population.

Adult↗
PubMed1998

Identification and characterization of the tumor suppressor p53 in channel catfish (Ictalurus punctatus).

Herein is presented the sequence of a catfish full-length p53 cDNA obtained from a cloned B cell line cDNA library. Southern blot analyses determined that a restriction fragment linked polymorphism (RFLP) existed with PstI among outbred catfish. Western blot analyses demonstrated that, when compared to PBLs, the catfish leukocyte lines express higher levels of p53 protein. Additionally, the results of Western blot analyses and in vitro translation experiments suggest that the catfish leukocyte lines may produce truncated forms of p53 due to internal initiation.

Amino Acid Sequence↗
PubMed1998

Apoptosis: unmasking the executioner.

The execution phase of apoptosis is comprised of those processes that commit cells to apoptotic death. Many independent studies have implicated mitochondria as playing a critical role in apoptotic execution. The activation of caspase-3 and subsequent late stage degradative events are probably triggered by the release of proteins (such as cytochrome c) from the intermembrane space of mitochondria. The mechanisms responsible for this release are controversial but may include mitochondrial permeability transition and bcl-2-regulated swelling of the mitochondrial matrix. Two theoretical models of execution are discussed. It is important to note that some critical features of these models are largely based on data acquired from cell-free studies. Further studies with intact cells are urgently needed to test the physiological validity of these models.

Animals↗
PubMed1998

Evolutionary variation of immunoglobulin mu heavy chain RNA processing pathways: origins, effects, and implications.

Immunoglobulins (Ig) can occur in two physical forms, soluble (secreted) and membrane bound. The soluble form is secreted from B cells, and is present in the blood and other fluids where it plays a role as an immune effector molecule. The membrane-bound form of the Ig molecule is inserted into the B-cell membrane, where it serves as a receptor for antigen. The function of the membrane-bound Ig as a receptor for antigen requires additional accessory molecules, the membrane Ig plus accessory molecules are referred to, collectively, as the B-cell receptor (BCR) complex. The secreted and membrane-bound forms of an Ig result from alternative patterns of RNA processing of the primary transcript from the heavy chain gene. IgM is the only class of Ig known to be conserved in all vertebrate species (perhaps exclusive of the agnathan fish). While the structure of the IgM heavy (mu) chain gene has been highly conserved in vertebrate evolution, the patterns of alternative RNA processing of the mu transcript show surprising diversity. In particular, the bony fish (teleosts) produce membrane mu-chain message by a splicing pathway that is quite different from that seen in other vertebrates; it results in the production of membrane IgM that lacks the C mu 4 domain. How this unusual RNA splicing pattern could have evolved and its implications for the function of the BCR in the bony fishes are considered here.

Animals↗