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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 91 records · Page 5Linked to original sources

Prevalence and antibiotic resistance profile of mercury-resistant oral bacteria from children with and without mercury amalgam fillings.

Genes encoding resistance to mercury and to antibiotics are often carried on the same mobile genetic element and so it is possible that mercury-containing dental materials may select for bacteria resistant to mercury and to antibiotics. The main aim of this study was to determine whether the prevalence of Hg-resistant oral bacteria was greater in children with mercury amalgam fillings than in those without. A secondary aim was to determine whether the Hg-resistant isolates were also antibiotic resistant. Bacteria in dental plaque and saliva from 41 children with amalgam fillings and 42 children without such fillings were screened for mercury resistance by cultivation on a HgCl(2)-containing medium. Surviving organisms were identified and their susceptibility to mercury and to several antibiotics was determined. Seventy-eight per cent and 74% of children in the amalgam group and amalgam-free group, respectively, harboured Hg-resistant bacteria; this difference was not statistically significant. Nor was there any significant difference between the groups in terms of the proportions of Hg-resistant bacteria in the oral microflora of the children. Of Hg-resistant bacteria, 88% and 92% from the amalgam group and the amalgam-free group, respectively, were streptococci; 41% and 33% were resistant to at least one antibiotic, most frequently tetracycline. The results of this study show that there was no significant difference between children with amalgam fillings and those without such fillings with regard to the prevalence, or the proportion, of Hg-resistant bacteria in their oral microflora. The study also found that Hg-resistant bacteria were common in children regardless of whether or not they had amalgam fillings and that many of these organisms were also resistant to antibiotics.

Adolescent↗

Comparison of lysis filtration and an automated blood culture system (BACTEC) for detection, quantification, and identification of odontogenic bacteremia in children.

Lysis filtration (LyF) was compared with BACTEC PAEDS PLUS in estimating the prevalence of, and sensitivity for, detection of odontogenic bacteremia. Both real bacteremia and simulated bacteremia (seeded blood or saline samples) were assessed to determine the validity of LyF in estimating bacteremia. The simulated bacteremia was also used to assess the reliability of LyF to estimate intensity of bacteremia in CFU per milliliter of blood. Reference organisms were used to assess the abilities of LyF and BACTEC to isolate known oral streptococci. There was no difference in the number of CFU per milliliter of seeded saline, seeded blood, and drop cultures of the organisms plated directly onto agar. Blood cell volume had a negligible effect on the yield of organisms for simulated bacteremia. When LyF and BACTEC were compared, the time to detection of bacteremia was always significantly shorter for BACTEC. For aerobic cultures, these times were 43.7 and 9.6 h, respectively (P < 0.01). For anaerobic cultures, these times were 45.1 and 9.9 h, respectively (P < 0.01). These differences occurred as well for bacteremia following the extraction of a single tooth, with LyF and BACTEC aerobic cultures taking 78 and 30.5 h, respectively (P < 0.0001). For anaerobic cultures, the times were 90.8 and 45 h, respectively (P < 0.0004). A preextraction bacteremia was detected on 2.1% of occasions with BACTEC compared to 31% of occasions with LyF (P < 0.05) The use of LyF was an effective and reliable means of estimating the intensity of pre- and postextraction bacteremia. The values were 3.6 and 5.9 CFU/ml, respectively (P < 0.4729), and the difference was not statistically significant. In summary, BACTEC is quicker than LyF, but less sensitive. LyF provides additional important information in estimating the intensity of bacteremia.

Adolescent↗

Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.

Age Factors↗

Women's acceptability of screening for HIV in pregnancy.

AIMS: To elicit acceptability of HIV screening during pregnancy in women of reproductive age in Christchurch. METHODS: In-depth face-to-face interviews were conducted with women of reproductive age recruited from seven different service sites in Christchurch. RESULTS: Women wanted to know about treatment that significantly reduces the risk of mother-to-child transmission. They wanted to know about other antenatal screening and were prepared to provide general consent, rather than specific consent for HIV testing. All study participants favoured routine offer of HIV testing during pregnancy for all women and most would agree to be tested, if the test was offered and recommended. CONCLUSIONS: The results of this study indicate the need to develop and test a user-friendly approach for offering routine HIV testing during standard antenatal care in New Zealand.

AIDS Serodiagnosis↗

Toxoplasma gondii infection in the United States: seroprevalence and risk factors.

Infection with Toxoplasma gondii can cause severe illness when the organism is contracted congenitally or when it is reactivated in immune-suppressed persons. To determine the prevalence of T. gondii infection in a representative sample of the US population, the authors tested sera from participants in the Third National Health and Nutrition Examination Survey (1988-1994) for immunoglobulin G antibodies to T. gondii. Of 27,145 persons aged > or =12 years, 17,658 (65%) had sera tested. The overall age-adjusted seroprevalence was 22.5% (95% confidence interval (CI): 21.1, 23.9); among women aged 15-44 years, seroprevalence was 15.0% (95% CI: 13.2, 17.0). Age-adjusted seroprevalence was higher in the Northeast (29.2%) than in the South (22.8%), Midwest (20.5%), or West (17.5%) (p < 0.05). In multivariate analysis, risk for T. gondii infection increased with age and was higher among persons who were foreign-born, persons with a lower educational level, those who lived in crowded conditions, and those who worked in soil-related occupations, although in subset analyses risk categories varied by race/ethnicity. Nearly one quarter of adults and adolescents in the United States have been infected with T. gondii. Most women of childbearing age in the United States are susceptible to acute infection and should be educated about ways to minimize exposure to T. gondii.

Adolescent↗

The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice.

This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11g (R1 = meta-CF(3), Ar2 = 4'biphenyl, R3 = diethylamide) illustrated the potency of this series with ED(50) values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.

Acetamides↗

Heterogeneity of channel catfish CTL with respect to target recognition and cytotoxic mechanisms employed.

Two types of catfish alloantigen-dependent cytotoxic T cells were cloned from PBL from a fish immunized in vivo and stimulated in vitro with the allogeneic B cell line 3B11. Because these are the first clonal cytotoxic T cell lines derived from an ectothermic vertebrate, studies were undertaken to characterize their recognition and cytotoxic mechanisms. The first type of CTL (group I) shows strict alloantigen specificity, i.e., they specifically kill and proliferate only in response to 3B11 cells. The second type (group II) shows broad allogeneic specificity, i.e., they kill and proliferate in response to several different allogeneic cells in addition to 3B11. "Cold" target-inhibition studies suggest that group II CTL recognize their targets via a single receptor, because the killing of one allotarget can be inhibited by a different allotarget. Both types of catfish CTL form conjugates with and kill targets by apoptosis. Killing by Ag-specific cytotoxic T cells (group I) was completely inhibited by treatment with EGTA or concanamycin A, and this killing is sensitive to PMSF inhibition, suggesting that killing was mediated exclusively by the secretory perforin/granzyme mechanism. In contrast, killing by the broadly specific T cytotoxic cells (group II) was only partially inhibited by either EGTA or concanamycin A, suggesting that these cells use a cytotoxic mechanism in addition to that involving perforin/granzyme. Consistent with the presumed use of a secretory pathway, both groups of CTL possess putative lytic granules. These results suggest that catfish CTL show heterogeneity with respect to target recognition and cytotoxic mechanisms.

Animals↗

Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease.

Hirschsprung disease (HD) has been described in association with microcephaly, mental retardation and characteristic facial features, delineating a syndrome possibly caused by mutations localized at chromosome 2q22--q23. We have analyzed a de novo translocation breakpoint at 2q22 in one patient presenting with this syndrome, and identified a gene, SIP1, which is disrupted by this chromosomal rearrangement. SIP1 encodes Smad interacting protein 1, a new member of the delta EF1/Zfh-1 family of two-handed zinc finger/homeodomain transcription factors. We determined the genomic structure and expression of the human SIP1 gene. Further analysis of four independent patients showed that SIP1 is altered by heterozygous frameshift mutations causing early truncation of the protein. SIP1, among other functions, seems to play crucial roles in normal embryonic development of neural structures and neural crest. Its deficiency, in altering function of the TGF beta/BMP/Smad-mediated signalling cascade, is consistent with some of the dysmorphic features observed in this syndrome, in particular the enteric nervous system defect that underlies HD.

Abnormalities, Multiple↗

Infectious disease pathology.

The anatomic pathologist performs an important role in the diagnosis or exclusion of infectious diseases. The morphologic interpretation of biopsies and cytologic preparations allows for the definitive establishment or exclusion of a wide variety of diseases. Once the pathologist has determined that a disease is likely to be due to an infection and has characterized the inflammatory response, associated microorganisms or viral-associated cytopathic effects should be recorded. Although some microorganisms or their cytopathic effects may be clearly visible on routine hematoxylin and eosin-stained sections, additional histochemical stains are often needed for their complete characterization. Highly specific molecular techniques, such as immunohistochemistry, in situ hybridization, and nucleic acid amplification, may be needed in certain instances to establish the diagnosis of infection. Through appropriate morphologic diagnoses and interlaboratory communication and collaboration, the anatomic pathologist contributes greatly to the diagnosis and treatment of infectious diseases.

Animals↗

Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?

Breast cancer risk is substantially lower in Singapore than in women from the United STATES: Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha-hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los ANGELES: We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E(1)), estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16alpha-OHE(1) levels or in the ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2-OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of 2OHE(1):16alpha-OHE(1.)

Aged↗

Thioredoxin acts as a B cell growth factor in channel catfish.

To identify differentially expressed genes from channel catfish macrophages, a cDNA library from LPS-stimulated catfish macrophages was screened by subtractive hybridization. This screening yielded a 552-bp cDNA coding for catfish thioredoxin (CF-TRX). The deduced amino acid sequence revealed that CF-TRX contains 107 amino acids and is 59% homologous to human adult T cell leukemia-derived factor/TRX, originally described as an IL-2R alpha-inducing factor. Northern blot analyses showed that CF-TRX is expressed in catfish T and macrophage cell lines, but weakly in B cell lines. Similar results were also observed in Western blot analyses using a mAb specific for recombinant CF-TRX (rTRX). The use of rTRX in functional studies demonstrated that rTRX induces in vitro proliferative responses of catfish PBL that were synergistically enhanced by the addition of culture supernatants from catfish T cell lines. In addition, cell separation studies and flow cytometric analyses revealed that the cells proliferating in rTRX-stimulated cultures were mostly B cells. These results suggest that CF-TRX may have an important role in the activation and proliferation of channel catfish B cells.

Amino Acid Sequence↗

The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer.

Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell survival. Current models suggest that an increase in Ang-2 expression in endothelial cells leads to initiation of angiogenesis. We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone, injected the cells s.c. into nude mice, and assessed tumor growth. Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the tumors. The tumors produced by the Ang-2-transfected cells were larger than the tumors produced in the other groups; those tumors also had higher vessel counts and proliferative indices than tumors in the other groups. Tumors produced by the Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices than tumors in the other groups. These data suggest that imbalances between Ang-1 and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor angiogenesis and growth.

Angiopoietin-1↗

Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

Amidines↗

Nocardia asteroides native valve endocarditis.

A 39-year-old man with a history of injection drug abuse was given a diagnosis of Nocardia asteroides native aortic valve endocarditis, and he required valve replacement therapy, despite having received potent antimicrobial therapy. This is the first reported proven case of native valve endocarditis due to Nocardia species.

Adult↗

Analysis of the effect of changing environmental conditions on the expression patterns of exported surface-associated proteins of the oral pathogen Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans has been specifically implicated in the aetiology of one or more of the periodontal diseases, conditions in which inflammation of the gums is associated with destruction of the alveolar bone supporting the teeth. In these diseases there is loss of attachment of the gums (gingivae) to the teeth forming a periodontal pocket. The microenvironment of this pocket is extremely complex and it is likely that there will be substantial variation in the environmental conditions operating in this habitat. The aim of the current investigation was to study the effect of disease-relevant environmental factors on the production and release of secreted surface- associated proteins of A. actinomycetemcomitans. These secreted proteins contain many of the virulence determinants of this organism. A range of environmental conditions were investigated: growth in a CO(2)-enriched aerobic atmosphere vs anaerobic growth, presence of serum or blood, biofilm vs planktonic mode of growth and iron depletion. Differential expression of a number of the secreted surface-associated proteins was observed under different growth conditions and these included the glycolytic enzyme triose phosphate isomerase. An ability to adapt to prevailing environmental conditions may facilitate the survival of the organism in the changing microIenvironment of the periodontal pocket.

Adaptation, Biological↗

Identification of photolabile outer membrane proteins of Porphyromonas gingivalis.

As the prevalence of antibiotic-resistant strains of bacteria increases, novel ways of treating infections need to be developed. This is particularly pertinent with respect to the periodontal diseases--the most common chronic bacterial infections of man. The use of a photosensitizer in combination with red light has been demonstrated to be effective in killing several human pathogens, including the oral bacterium, Porphyromonas gingivalis, a major pathogen in periodontitis. Killing was associated with alterations in the molecular masses of several outer membrane and plasma membrane proteins and these may be therapeutic targets for photodynamic therapy and other antimicrobial approaches. To identify these photolabile proteins, we have used a panel of monoclonal antibodies raised to whole P. gingivalis. A number of the antibodies recognized various photolabile proteins. Using a combination of Western blotting and protein sequencing the predominant photolabile proteins in P. gingivalis have been identified as the major secreted/cell surface proteases--Lys and Arg gingipain.

Adhesins, Bacterial↗