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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 181 records · Page 10Linked to original sources
PubMed1995

Subinhibitory concentrations of cefpodoxime alter membrane protein expression of Actinobacillus actinomycetemcomitans and enhance its susceptibility to killing by neutrophils.

The aim of the present study was to determine the effect of the antibiotic cefpodoxime on the gram-negative periodontopathic microorganism Actinobacillus actinomycetemcomitans and its interaction with elements of the host immune system. Growth of A. actinomycetemcomitans in subinhibitory concentrations of cefpodoxime induced morphological changes in the bacteria, causing the organisms to grow as filaments rather than coccobacilli. Growth in cefpodoxime did not render these bacteria susceptible to killing by serum, nor did it abrogate the requirement for serum opsonins to support the bactericidal activity of neutrophils. Cefpodoxime enhanced the susceptibility of A. actinomycetemcomitans to the bactericidal activity of neutrophils. In the presence of suitable opsonins, neutrophils were able to kill four times as many cefpodoxime-induced A. actinomycetemcomitans filaments as untreated A. actinomycetemcomitans CFU. This effect was due to antibiotic actions on the bacterium and not on the neutrophil. At inhibitory concentrations, the bactericidal activities of cefpodoxime and neutrophils were additive, and cefpodoxime did not interfere with the normal functioning of the neutrophils. Concomitant with these morphological and functional changes, the expression of two outer membrane proteins (66 and 29 kDa) and one inner membrane protein (57 kDa) was decreased in A. actinomycetemcomitans grown in cefpodoxime. The concentration range over which cefpodoxime is effective against A. actinomycetemcomitans in vivo may be extended by the ability of subinhibitory concentrations to enhance the susceptibility of this organism to host immune defenses.

Adult↗
PubMed1995

Immunoglobulin G subclass response of juvenile periodontitis subjects to principal outer membrane proteins of Actinobacillus actinomycetemcomitans.

The cell envelope of Actinobacillus actinomycetemcomitans includes a number of outer membrane proteins (OMPs) which appear to be important targets for immunoglobulin G (IgG) antibodies in sera from localized juvenile periodontitis (LJP) patients. In this study, we examined the subclass distribution of IgG antibodies reactive to the 16.6- and 29-kDa OMPs of A. actinomycetemcomitans in sera from LJP patients and periodontally healthy individuals. Antibody responses were determined in a quantitative enzyme-linked immunosorbent assay that employed human IgG subclass-restricted monoclonal antibodies. High-titer LJP sera (93% black; geometric mean titer, 32,673) were found to contain significantly elevated levels of IgG1, IgG2, and IgG3 antibodies to the 29-kDa OMP of A. actinomycetemcomitans, compared with those of low-titer LJP sera (mean titer, 1,421) and sera from periodontally healthy, race-matched control subjects. The concentration of IgG2 antibody to this protein was greater than or equal to the corresponding IgG1 concentration in 7 of 14 high-titer sera, although mean IgG1 and IgG2 concentrations were not significantly different. The concentrations of IgG1 and IgG2 antibodies to the 16.6-kDa protein were also significantly elevated in LJP sera, although of considerably lesser magnitude than that observed for the 29-kDa protein. The IgG2 response to the 29-kDa protein could not be attributed to the presence of IgG2 antibodies to lipopolysaccharide contaminants or to Fc-binding activity, nor does this molecule appear to be a glycoprotein. Hence, LJP subjects produce IgG2 antibodies, as well as IgG1 and IgG3 antibodies, directed to at least one of the major OMPs of A. actinomycetemcomitans.

Adolescent↗
PubMed1995

Immunoglobulin G2 antibodies promote neutrophil killing of Actinobacillus actinomycetemcomitans.

Sera from patients with localized juvenile periodontitis (LJP) often contain markedly elevated levels of immunoglobulin G2 (IgG2) antibodies reactive to cell envelope constituents of Actinobacillus actinomycetemcomitans. The objective of this study was to determine if these IgG2 antibodies are capable of supporting phagocytosis and killing of A. actinomycetemcomitans by human neutrophils. Polyclonal IgG2 antibodies were prepared from high-titer LJP serum by affinity chromatography, yielding a preparation which was > 99% subclass restricted and retained immunoreactivity to A. actinomycetemcomitans antigens. Affinity-purified IgG2 antibodies were evaluated by an in vitro opsonophagocytic assay that employed neutrophils obtained from donors who were homozygous for the H131 allotype of Fc gamma receptor type IIa (CD32), which efficiently binds human IgG2 antibodies. Affinity-purified IgG2 antibodies from LJP serum but not from sera of periodontally healthy individuals promoted phagocytosis and killing of A. actinomycetemcomitans. The expression of IgG2-dependent opsonic activity required the presence of complement. Incubation of A. actinomycetemcomitans with neutrophils in the presence of an optimal concentration of LJP IgG2 (50 micrograms/ml) and 5% hypogammaglobulinemic serum (as a complement source) resulted in a > 1 log10 reduction in bacterial viability within 30 min. The opsonic activity of IgG2 antibodies was found to be comparable to that observed with affinity-purified IgG1 antibodies. Moreover, IgG1 antibodies interacted synergistically with IgG2 antibodies in promoting opsonophagocytosis of A. actinomycetemcomitans. The results of this study indicate that LJP serum contains IgG2 antibodies which, when employed in conjunction with neutrophils that express Fc gamma receptors capable of recognizing this subclass, are opsonic for A. actinomycetemcomitans.

Agammaglobulinemia↗
PubMed1995

A recombinant Leishmania chagasi antigen that stimulates cellular immune responses in infected mice.

Cellular immune mechanisms resulting in gamma interferon production are critical for protection against visceral leishmaniasis. Antigens stimulating T-cell responses are likely present in the intracellular amastigote form of the parasite, since this is the form found in a mammalian host. To identify T-cell antigens of Leishmania chagasi, the parasite causing South American visceral leishmaniasis, we used a double antibody-T-cell technique to screen an amastigote cDNA library. One cDNA selected (Lcr1) encodes an antigen that stimulated proliferation of splenic T lymphocytes from infected mice that were either resistant (C3H.HeJ) or susceptible (BALB/c) to L. chagasi infection. The Lcr1 cDNA contains four highly divergent 201-bp repeats homologous to the 204-bp repeat of a Trypanosoma cruzi flagellar antigen gene. Results are consistent with a single copy of the Lcr1 gene producing an mRNA of > 10 kb and a protein of > 200 kDa. Recombinant Lcr1, cloned adjacent to polyhistidine and purified on a nickel affinity column, stimulated gamma interferon but not interleukin-4 (IL-4), IL-5, or IL-10 secretion by T-cell-enriched splenocytes from either susceptible or resistant mice during L. chagasi infection. Immunization with Lcr1 partially protected BALB/c mice against challenge with L. chagasi, indicating the utility of the double screening approach in selecting relevant T-cell antigens.

Amino Acid Sequence↗
PubMed1995

Effect of aging on animal response to chronic fluoride exposure.

This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.

Age Factors↗
PubMed1995

In-home injury prevention practices for infants and toddlers: the role of parental beliefs, barriers, and housing quality.

The present research was designed to contribute to the empirical literature on the scope and determinants of parents' injury prevention practices among families living in disadvantaged, urban areas. One hundred fifty mothers were interviewed about their living environment when they brought their children (ages 6-36 months) to a hospital-based, pediatric primary care clinic. Only 37% of respondents reported that they knew their hot water temperature was 125 degrees or less. A majority (59%) of families reported that they did not use stair gates. More than one fourth (27%) of respondents said they did not have smoke detectors. Mothers uniformly reported very favorable attitudes and beliefs and strong support from others for in-home injury prevention practices. Factors significantly associated with the number of injury prevention practices implemented were family income, housing quality, and environmental barriers. Instead of attempting solely to persuade parents about the value of injury prevention practices, skill-based interventions are needed to help parents overcome specific barriers that result from living in substandard housing and having very limited financial resources.

Accident Prevention↗
PubMed1995

IGF-I administration advances the decrease in hypersensitivity to oestradiol negative feedback inhibition of serum LH in adolescent female rhesus monkeys.

Developmental increases in serum LH were assessed in female rhesus monkeys to test the hypotheses that (1) the final stages of puberty are characterized by a decrease in hypersensitivity to oestradiol negative feedback of LH and (2) that increases in IGF-I secretion accelerate this decrease in hypersensitivity. In order to test the first hypothesis, serum LH in the absence of oestradiol and in response to three doses of oestradiol were compared between ovariectomized adult (n = 6) and adolescent female monkeys (control group; n = 6). The control females were not treated with oestradiol until serum LH had risen to within the 95% confidence interval of serum LH observed in ovariectomized adults. Doses of oestradiol achieved serum levels of approximately 80 ('low'), 160 ('intermediate'), and 250 ('high') pmol/l. For control group females, treatment with the next higher dose of oestradiol was not initiated until serum LH was no longer suppressed by the lower dose. Treatment with oestradiol produced a dose-dependent suppression in serum LH in adults. In contrast, low-dose oestradiol maximally suppressed serum LH throughout the initial treatment period in the control group compared with the adult females. The low oestradiol dose effectively suppressed serum LH throughout the study period in 4/6 of the control group and became ineffective at suppressing LH after 8 months of treatment in 2/6 control group females. Initiation of the intermediate dose of oestradiol to these females again maximally suppressed LH compared with adult females. In order to determine whether IGF-I regulates this change in hypersensitivity to oestradiol negative feedback, a second group of ovariectomized, adolescent monkeys (n = 6) were treated chronically with IGF-I to elevate serum IGF-I levels above those of control group females. Using the same protocol described for the control females, developmental changes in serum LH in the absence of oestradiol and in response to oestradiol negative feedback were evaluated. Treatment with IGF-I had no effect on the initial increases in serum LH occurring in the absence of oestradiol. In contrast, the decrease in hypersensitivity to the negative feedback effects of the low oestradiol dose was significantly accelerated in IGF-I-treated females, as the interval from the initiation of treatment to the point at which serum LH was no longer suppressed was shorter in IGF-I-treated (4.4 +/- 0.7 months; mean +/- S.E.M.) compared with control group females (8.4 +/- 1.9 months).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Dust suppression in swine feed using soybean oil.

Dust generation from swine feed (corn-soybean meal diet) treated with soybean oil was investigated using a cement mixer in a plywood box. Airborne total dust concentrations in the box were measured gravimetrically using a vacuum pump and filters while 12-kg feed samples were constantly mixed. The treatment factors were soybean oil concentration (0, 1, and 3%), corn bulk density (normal, 730 kg/m3 and low, 600 kg/m3), time of oil addition (before vs after grinding the corn), and storage time (0, 7, and 14 d). The feed was a mixture of soybean meal, base mix, and adjusted amounts of ground corn and soybean oil. Adding soybean oil after grinding at 1 and 3% levels to feed made with normal-bulk density corn suppressed total dust generation (3.39 and .99 mg/m3, respectively) (P < .001) compared with the no oil treatment (29.1 mg/m3). The 3% soybean oil treatment suppressed dust generation (.99 mg/m3) more than the 1% soybean oil treatment (3.39 mg/m3) (P < .001). Adding soybean oil after grinding the corn suppressed dust generation more than adding the oil to the corn before grinding for every oil level (P < .001). More dust was generated by feed made from low-bulk density corn than by feed made with normal-bulk density corn at every oil level (P < .001). There was no evidence of any storage time or treatment x storage time interactions.

Animal Feed↗
PubMed1995

The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.

OBJECTIVE: To quantify the efficacy of vaccination of infants with bacillus Calmette-Guérin (BCG) against tuberculosis. DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations. STUDY SELECTION: A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1-RR or 1-OR. Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. CONCLUSION: BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis--by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

BCG Vaccine↗
PubMed1994

Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature.

OBJECTIVE: To quantify the efficacy of BCG vaccine against tuberculosis (TB). DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies. STUDY SELECTION: A total of 1264 articles or abstracts were reviewed for details on BCG vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable groups, equal surveillance and follow-up for recipient and concurrent control groups, and outcome measures of TB cases and/or deaths. Fourteen prospective trials and 12 case-control studies were included in the analysis. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, and items to assess the potential for bias in study design and diagnosis. At least two readers independently extracted data and evaluated validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) of TB provided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1-RR or 1-OR. A random-effects model estimated a weighted average RR or OR from those provided by the trials or case-control studies. In the trials, the RR of TB was 0.49 (95% confidence interval [CI], 0.34 to 0.70) for vaccine recipients compared with nonrecipients (protective effect of 51%). In the case-control studies, the OR for TB was 0.50 (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29; 95% CI, 0.16 to 0.53), and five studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR, 0.36; 95% CI, 0.18 to 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model. CONCLUSION: On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against tuberculous death, meningitis, and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy.

BCG Vaccine↗
PubMed1994

Somatostatin mRNA levels within the periventricular nucleus are regulated by estradiol and insulin-like growth factor-I in immature female rats.

Adolescent growth is regulated by developmental increases in growth hormone (GH) secretion. Although the hypothalamic release of GH-releasing hormone (GHRH) stimulates and the release of SRIF inhibits GH secretion, it is not known how these regulatory mechanisms change developmentally. In addition, GH secretion is facilitated during maturation by increases in peripheral estradiol and may be inhibited, via a negative feedback mechanism, by insulin-like growth factor-I (IGF-I). It is not clear whether these act through the hypothalamic regulation of GHRH and somatostatin (SRIF). In order to further understand the regulation of GH secretion during development, the present study determined how estradiol and IGF-I altered SRIF mRNA in the hypothalamus in immature female rats. The working hypotheses were that estradiol would decrease SRIF mRNA accounting, in part, for its positive effect on GH release and IGF-I would increase SRIF mRNA representing a negative feedback mechanism regulating GH secretion. Preprosomatostatin (ppSRIF) mRNA levels within the periventricular nucleus (PeVN) were measured with in situ hybridization in ovariectomized female rat pups (n = 5 per group). Infusions were delivered sc via either a Silastic capsule (oil, 10 or 60 micrograms/ml estradiol) or an osmotic minipump (acetic acid, 120 or 240 micrograms IGF-I/day). Following ovariectomy on Day 21, animals were treated for either 1 or 7 days beginning on Day 24 of age. A total of 18 treatment groups were evaluated, including control, estradiol alone, IGF-I alone, and estradiol and IGF-I combined at both doses and treatment durations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗