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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 325 records · Page 18Linked to original sources

A toxic metabolite of Nigrospora oryzae (Berk and Br.) petch.

Nigrospora oryzae was isolated from dallisgrass (Paspalum dilatatum Poir.) collected in Auburn and from hay shipped under refrigeration to Florida. Some of these samples were eaten by cattle and horses that subsequently developed lameness. Metabolites of N. oryzae were separated by thin layer chromatography and tested for toxicity. Only one metabolite was toxic. Metabolite A showed toxicity to brine shrimp with an LD50 = 500 micrograms/ml in 8 h. It also had an antibiotic effect on Bacillus megaterium ATCC 14581 with a minimum inhibitory level of 10.1 micrograms/disc. As little as 435 micrograms of a crude methanolic extract of N. oryzae showed mild toxicity to chick embryos. The metabolite was not toxic to mice nor rats at the levels tested. Quantitative procedures developed for the determination of metabolite A showed that the maximum production occurred in yeast extract-sucrose liquid medium with an initial pH of 5-6, when incubated as a stationary culture for 28 days at 25 degrees C. It was concluded that metabolite A is a weak antibiotic rather than a mycotoxin, and was probably not associated with the symptoms of lameness observed in cattle and horses. The antibiotic is not one previously reported for N. oryzae.

Animal Feed↗

Steroidogenesis by the immature rhesus monkey ovary in vitro.

Primates are believed to have a low level of ovarian steroidogenic activity during prepubertal development. In order to study the rate limiting factors associated with the low level of steroidogenesis, ovaries from prepubertal rhesus monkeys were quartered and incubated for 48 h at 37 C in minimum essential medium. These ovaries secreted 687 +/- 347 pg estradiol/mg ovary and 299 +/- 35 pg progesterone/mg ovary during 48 h of incubation. The addition of 100 ng luteinizing hormone (LH) or 1 mM dibutyryl (Bu)2 cAMP failed to increase significantly estradiol or progesterone secretion. Furthermore, the addition of either progesterone or androstenedione failed to augment estradiol secretion. The presence of either LH or (Bu)2 cAMP with the steroidal substrates also failed to augment estradiol secretion. In contrast, the addition of (Bu)2 cAMP with lipoprotein-derived cholesterol significantly stimulated a two-fold increase in progesterone secretion. The presence of LH in the lipoprotein-supplemented medium failed to augment progesterone secretion. These results suggest that prepubertal monkey ovaries lack the ability to respond to LH, probably due to a lack of gonadotropin receptors or failure of the receptor to stimulate cAMP synthesis. Furthermore, the failure of progesterone and androstenedione to augment estradiol secretion suggests that some cellular components needed to induce aromatase activity are not functional in the prepubertal primate ovary.

Androstenedione↗

Changes in the nucleoprotein complexes of a baculovirus DNA during infection.

The nature of the DNA-protein complexes assumed by Autographa californica nuclear polyhedrosis virus (AcNPV) DNA during infection of Spodoptera frugiperda cells was investigated by micrococcal nuclease digestion of infected nuclei. Both parental viral DNA and progeny viral DNA assumed a chromatin-like structure early in infection. By late times (24 hr) p.i., the viral DNA acquired a unique nucleoprotein structure. In addition to fragments of mononucleosome size (185 bp), two subnucleosomal bands of 120 and 90 bp were observed. The subnucleosomal bands contained exclusively viral DNA. No alteration in the nature of the host chromatin structure following AcNPV infection was observed. An examination of the basic chromatin-associated proteins revealed two major viral-induced proteins having molecular weights of 15K and 39K. The induction of the basic 15K protein between 10 and 24 hr p.i. coincided with the appearance of the altered nucleoprotein structure observed by 24 hr p.i. and the cessation of histone synthesis.

Animals↗

Retinoblastoma. A clinical, immunohistochemical, and electron microscopic case report.

A 4-year, 9-month-old boy had a history of leukocoria of the right eye for approximately six months prior to admission. The other eye was normal. There was no family history of retinoblastoma. Funduscopy disclosed a large white mass extending from the nasal pars plana to the mid-pupillary zone and the posterior pole with a near total retinal detachment in the superior temporal quadrant. A B-scan ultrasound showed an echo dense area of the anterior portion of the mass. A CT scan showed intraocular tissue densities with no evidence of optic nerve involvement or extraocular extension. Immunohistochemistry of a fresh frozen portion of tumor revealed reactivity with antibodies directed against interphotoreceptor retinoid-binding-protein (IRBP), neuron-specific enolase, glial fibrillary acidic protein, S-antigen, focal reactivity with opsin, and scattered cytoplasmic staining for cyclic GMP and cyclic GMP phosphodiesterase. Biochemical analysis of fresh frozen tissue samples confirmed the presence of IRBP. Transmission electron microscopy disclosed occasional Flexner-Wintersteiner rosettes connected by zonula adherens-like junctions. These showed inner segment-like structures containing prominent mitochondria, portions of cilia and fragments of outer segment material. These data, along with the immunocytochemistry indicates a predominant neuronal nature of the tumor cells with significant photoreceptor-like differentiation.

Child, Preschool↗

Age, social rank and lactational status influence ovulatory patterns in seasonally breeding rhesus monkeys.

Rhesus monkeys housed outdoors exhibit a distinct breeding season limited to the fall and winter months. Four groups of female rhesus monkeys, multiparous nonlactating (MNL; n = 8), multiparous lactating (ML; n = 6), primiparous lactating (PL; n = 3) and nulliparous first-time ovulators (N; n = 6) were studied to investigate the influence of age, parity, and social dominance rank on the parameters of the breeding season. MNL exhibited the longest season (146 days), and PL the shortest (70 days), with N (106 days) and ML (89 days) intermediate. PL females also had a significantly reduced percentage of normal ovulations compared to other groups. Neither body weight nor estimates of body fat were related to either the timing of the ovulatory season or the quality of ovulations within the season. Parity and social dominance rank were significantly related to the percentage of normal ovulations (r = 0.85), with low-ranking, primiparous females exhibiting the fewest normal ovulations. These data indicate that the presence of a suckling infant acts synergistically with environmental factors to determine the parameters of the breeding season. Furthermore, postpubertal females may be more responsive to those factors that terminate the breeding season, and some factor independent of body weight but associated with low social dominance rank and/or primiparity renders females less capable of normal luteal function during the breeding season.

Age Factors↗

Oxidative and nonoxidative killing of Actinobacillus actinomycetemcomitans by human neutrophils.

Actinobacillus actinomycetemcomitans is a facultative gram-negative microorganism which has been implicated as an etiologic agent in localized juvenile periodontitis and in subacute bacterial endocarditis and abscesses. Although resistant to serum bactericidal action and to oxidant injury mediated by superoxide anion (O2-) and hydrogen peroxide (H2O2), this organism is sensitive to killing by the myeloperoxidase-hydrogen peroxide-chloride system (K.T. Miyasaki, M.E. Wilson, and R.J. Genco, Infect. Immun. 53:161-165, 1986). In this study, we examined the sensitivity of A. actinomycetemcomitans to killing by intact neutrophils under aerobic conditions, under anaerobic conditions, and under aerobic conditions in the presence of the heme-protein inhibitor sodium cyanide. Intact neutrophils killed opsonized A. actinomycetemcomitans under aerobic and anaerobic conditions, and the kinetics of these reactions indicated that both oxidative and nonoxidative mechanisms were operative. Oxidative mechanisms contributed significantly, and most of the killing attributable to oxidative mechanisms was inhibited by sodium cyanide, which suggested that the myeloperoxidase-hydrogen peroxide-chloride system participated in the oxidative process. We conclude that human neutrophils are capable of killing A. actinomycetemcomitans by both oxygen-dependent and oxygen-independent pathways, and that most oxygen-dependent killing requires myeloperoxidase activity.

Actinobacillus↗

Killing of Actinobacillus actinomycetemcomitans by the human neutrophil myeloperoxidase-hydrogen peroxide-chloride system.

Actinobacillus actinomycetemcomitans is a facultative gram-negative coccobacillus associated with periodontal disease and nonoral infections. This organism is resistant to serum bactericidal mechanisms but is nevertheless killed by human neutrophils under aerobic and anaerobic conditions. Most of the killing attributable to oxidative mechanisms is inhibited by sodium cyanide, which suggests that the myeloperoxidase-hydrogen peroxide-chloride (MPO-H2O2-Cl-) system may be a key factor in the oxidative killing process. In this report, we examine whether the isolated MPO-H2O2-Cl- system is bactericidal against A. actinomycetemcomitans. We found that three major chromatographic forms of MPO were capable of killing A. actinomycetemcomitans at sublethal concentrations of H2O2 and that both catalase-positive and catalase-negative strains of this organism were sensitive to killing by the MPO-H2O2-Cl- system. We conclude that the isolated MPO-H2O2-Cl- system is bactericidal for A. actinomycetemcomitans independent of other neutrophil granule constituents and may be an important component of the oxygen-dependent bactericidal activity of the neutrophil with respect to this periodontopathic organism.

Blood Bactericidal Activity↗

Population ecology of the ring-tailed lemur, Lemur catta, and the white sifaka, Propithecus verreauxi verreauxi, at Berenty, Madagascar, 1981.

The diurnal lemurs Propithecus verreauxi verreauxi and Lemur catta at Berenty in southern Madagascar, have been studied for the last 30 years. The August 1981 census indicates that the population size of L. catta remains stable at 150 adults but that P. v. verreauxi troops have become fragmented and scattered and the population is apparently increasing. Eight different vegetation types were classified within the reserve and their influence on the distribution of L. catta and P. v. verreauxi investigated. Behavioural data obtained shows the niche separation between these two, potentially competitive, sympatric lemurs.

Animals↗

Antimicrobial properties of hydrogen peroxide and sodium bicarbonate individually and in combination against selected oral, gram-negative, facultative bacteria.

The topical application of hydrogen peroxide (H2O2) and sodium bicarbonate (NaHCO3), individually and in combination, has been used empirically in the treatment of periodontal diseases. In this study, we examined both minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of these disinfectants individually and in combination against selected facultative, Gram-negative oral bacteria in a microtiter dilution assay. The bacteria studied included Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Eikenella corrodens, and Capnocytophaga gingivalis. These bacteria exhibited MBC (one hr) values ranging from 75 mumol/L to greater than 10 mmol/L and MIC from less than 5 to 500 mumol/L for H2O2. The tested bacteria exhibited MIC values for NaHCO3 of from 23 to 182 mmol/L, and the MBC (one hr) exceeded 728 mmol/L for most of the strains examined. At sublethal (sub-MIC) concentrations, sodium bicarbonate antagonized the ability of H2O2 to inhibit bacterial growth in MIC assays, but sublethal concentrations of H2O2 had no effect on the MIC values of NaHCO3. Lethal concentrations of H2O2 and NaHCO3 exhibited synergistic antimicrobial activity in combination in one-hour bactericidal assays. Since the bactericidal properties of these antimicrobial agents are synergistic, we conclude that it may be rational to use them in combination to treat certain forms of periodontal disease. Also, lower and perhaps safer concentrations of H2O2 can be used in combination with NaHCO3 when oxidative antimicrobial chemotherapy is indicated.

Actinobacillus↗

1985 Kreshover lecture. Molecular factors influencing neutrophil defects in periodontal disease.

Major advances in our understanding of the role of the neutrophil in host defense against periodontal organisms have been made through studies of localized juvenile periodontitis (LJP). Several lines of evidence suggest that LJP is an infectious process closely associated with Actinobacillus (Haemophilus) actinomycetemomitans as a causative agent, although other organisms may also participate. The immunologic profile of LJP patients suggests that a cell-associated neutrophil locomotory dysfunction is a key underlying immunodeficiency resulting in increased susceptibility to periodontal infection. In addition, LJP patients often exhibit cervical lymphadenopathy and IgG-hypergammaglobulinemia, and a markedly elevated antibody response to the infecting organism, A. actinomycetemcomitans, is found in the serum and crevicular fluid of most patients. Evaluation of the locomotory properties of LJP neutrophils shows that random migration and chemokinesis are normal; however, about 70% of the LJP patients suffer from a defect in chemotaxis, with their neutrophils responding poorly to bacterial chemotactic factors, synthetic chemotactic peptides, and complement fragments (C5a). Depressed chemotaxis of LJP neutrophils is paralleled by their reduced capacity to bind the synthetic chemotactic peptide N-formylmethionylleucylphenylalanine (FMLP), as well as C5a. Furthermore, there is a reduction in the amount of glycoprotein 110, a neutrophil membrane matrix component and differentiation antigen which is associated with FMLP- and possibly also C5a-mediated chemotaxis. Reduction of C5a and of FMLP ligand binding, decreased expression of GP-110, and reduced neutrophil chemotaxis are consistent with a stem cell maturation error in LJP patients. This is further supported by studies demonstrating increased expression of CR2, the C3d/EBV receptor, on peripheral blood neutrophils of LJP patients. CR2 receptors are normally present on immature human neutrophils but are lost during the maturation process. These alterations in neutrophil surface components and their reduced chemotaxis may result from a genetically determined abnormality. Studies demonstrating the familial nature of both the neutrophil chemotactic disorder and the clinical entity represented by localized juvenile periodontitis point to a strong role for genetic determinants in the disease which affect neutrophil surface receptors.

Aggressive Periodontitis↗

Ontogeny of luteinizing hormone secretion and first ovulation in seasonal breeding rhesus monkeys.

A longitudinal analysis assessed the role of nongonadal control and estradiol (E2) inhibition of LH secretion during puberty in female rhesus monkeys and examined how maturational changes in LH release were related to GH secretion, ponderal growth, and seasonal changes in the environment. Three groups of spring-born monkeys housed outdoors were studied from 12 months of age in May 1982 through 43 months of age in December 1984: gonadally intact (INT; n = 8), ovariectomized (OVX; n = 5), and OVX E2 treated (E2OVX; n = 5; E2, approximately 45 pg/ml). Suppression of bioactive levels of LH by E2 was functional once changes in nongonadal control of LH release occurred, as basal LH levels increased significantly earlier in OVX (23.7 +/- 2.1 months) than either E2OVX (29.6 +/- 0.4 months) or INT (29.6 +/- 1.0 months). Although these increases in LH were not seasonally limited, higher levels were achieved if these initial increases occurred during the fall. Menarche in INT females occurred after the initial increases in LH (30.9 +/- 0.1 months). First ovulation for INT females was seasonally restricted, occurring either at 31.5 +/- 0.4 months in December/January (n = 3) or 11 months later at 42.5 +/- 0.4 months in October/November (n = 5). No ovulations occurred during the intervening spring and summer period, as serum levels of LH were significantly lower than in the preceding perimenarchial fall months. After the initial maturational increases, LH levels declined significantly in OVX and E2OVX females in late winter at 33 months before rising again the next fall. The timing and extent of the maturational decrease in E2 inhibition of LH secretion were related to developmental increases in serum GH and not to body weight. Furthermore, females who had a normal first ovulation shortly after menarche at 31 months had significantly higher serum GH levels yet similar growth rates and body weights compared to their age-mates. First ovulation at 43 months in the remaining females occurred after sustained elevations in serum GH, similar to those observed in the early ovulating females. These data indicate that both nongonadal control and steroid inhibition of LH secretion operate during puberty in female rhesus monkeys and support the hypothesis that the final stages of puberty are characterized by a maturational decrease in E2 negative feedback of LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Gonadal steroids influence serum somatomedin-C concentrations in prepubertal female rhesus monkey.

The present study examined the influence of estradiol (E2) and androstenedione (delta 4) on the regulation of GH and somatomedin-C (Sm-C) secretion in prepubertal female rhesus monkeys. Ovariectomized animals (n = 9) received empty capsules (0) or capsules filled with E2 or delta 4 in successive 2-week treatment blocks as follows: 0, E2, E2 plus delta 4, 0, delta 4, delta 4 plus E2, and 0. Serum samples were collected twice weekly for determination of basal hormone levels. Implantation of delta 4 capsules elevated serum delta 4 and testosterone concentrations, but did not influence E2 levels. Conversely, treatment with E2 only elevated serum E2. Basal concentrations of serum GH were unaffected by steroid treatment as levels varied between 5.5 and 9.5 ng/ml during the study. In contrast, Sm-C concentrations were increased significantly by each steroid treatment. Levels of Sm-C were elevated by delta 4 treatment (450.7 +/- 33.2 ng/ml) compared to baseline (376.2 +/- 37.7 ng/ml), whereas concentrations were maximally increased by E2 administration (greater than 600 ng/ml). The addition of delta 4 to the E2 treatment regimen did not further increase Sm-C levels. Regression analyses revealed that neither delta 4 nor testosterone concentrations were related to Sm-C or GH levels. In contrast, levels of E2 (r = 0.81) and GH (r = 0.42), which were not related to one another, were significantly correlated with Sm-C concentrations. Indeed, the multiple regression of E2 and GH on Sm-C accounted for significantly more variance in Sm-C levels (R2 = 0.706) than either hormone alone. These data suggest that E2 is responsible for the steroid-induced increases in Sm-C secretion observed previously in prepubertal females. Since steroid treatment elevated Sm-C levels independent of consistent changes in basal GH secretion, the effect is probably the result of either a direct E2 action on Sm-C release in the presence of a normal GH secretory pattern or an exacerbation of the nocturnal secretion of GH.

Androstenedione↗

Influence of endogenous catalase activity on the sensitivity of the oral bacterium Actinobacillus actinomycetemcomitans and the oral haemophili to the bactericidal properties of hydrogen peroxide.

Actinobacillus actinomycetemcomitans and the genetically-related oral haemophili (Haemophilus segnis, Haemophilus aprhophilus and Haemophilus paraphrophilus) exhibit a range of sensitivities to the lethal effect of hydrogen peroxide (H2O2), A. actinomycetemcomitans being the most resistant. To extend this information, susceptibility to a range of H2O2 concentrations (10(-6)-10(-3) M) was assessed by incubating bacterial suspensions for 1 h at 37 degrees C in the presence of H2O2 and spreading the suspensions on chocolate agar plates to determine the concentration of H2O2 producing a 50 per cent reduction in colony-forming units (LD50). Catalase activity was quantified with a Clark-type oxygen electrode, which polarographically monitored the formation of dissolved oxygen in bacterial suspensions or sonicates following addition of reagent H2O2. Sensitivity to H2O2 did not correlate with catalase activity, either in intact cells or in bacterial sonicates. Specifically, some bacterial strains with undetectable catalase activity were highly resistant to H2O2. Micromolar concentrations of sodium azide which completely inhibited cell-associated catalase activity did not affect the resistance of A. actinomycetemcomitans to H2O2. Thus, the endogenous catalase activity of A. actinomycetemcomitans and certain oral haemophili is not an important determinant of resistance to the bactericidal effects of H2O2.

Actinobacillus↗

Sensitivity of Capnocytophaga species to bactericidal properties of human serum.

Capnocytophaga is a newly described genus of gram-negative bacteria which can cause serious oral and extraoral infections in the susceptible host. In the present study, sensitivity of Capnocytophaga spp. to the bactericidal properties of human serum was investigated. Laboratory strains representative of Capnocytophaga sputigena, C. ochracea, and C. gingivalis and seven oral isolates of Capnocytophaga spp. obtained in primary culture were determined to be sensitive to killing by pooled normal serum. In contrast, little or no killing of Capnocytophaga spp. was observed when these organisms were incubated in the presence of hypogammaglobulinemic serum despite evidence for alternative pathway activation. However, hypogammaglobulinemic serum could be reconstituted to bactericidal activity by the addition of the immunoglobulin M fraction of normal serum. Capnocytophaga spp. failed to activate the classical pathway in hypogammaglobulinemic serum, thus ruling out an antibody-independent mechanism of killing. In contrast, good correlation was observed between serum-mediated killing and antibody-dependent classical pathway consumption. These results indicate that complement in the presence of bactericidal antibody may be an important determinant of host resistance to intra- and extraoral infections caused by Capnocytophaga spp.

Adult↗

Gonadal status influences developmental patterns of serum prolactin in female rhesus monkeys housed outdoors.

Although estradiol (E2) is thought to facilitate PRL secretion under certain conditions in female primates, the role of E2 or other ovarian products in the control of PRL secretion during puberty is unknown. The present study examined the influence of gonadal status on serum PRL levels in prepubertal monkeys housed in an outdoor environment. Basal levels of PRL were examined in three groups of spring-born females that were studied from 12 to 28 months of age (May 1982 to September 1983): gonadally intact (INT; n = 8), ovariectomized (OVX; n = 5), and ovariectomized and treated chronically with E2 (E2OVX; n = 5). All groups exhibited a significant annual rhythm in PRL levels with peaks (10-20 ng/ml) at 14 and 26 months (June to July) and a nadir (less than 2 ng/ml) at 19 months (November to December). Basal PRL levels were significantly higher from 12 to 15 months (May to August) in E2OVX subjects, with OVX having significantly greater concentrations than INT females. Group differences were not evident during the period of minimal secretion from 16 to 20 months (September to January). Finally, levels were again significantly higher in both E2OVX and OVX subjects during the subsequent period from 21 to 27 months (February to August). Although serum levels of E2 were lower in INT (30.9 +/- 2.3 pg/ml) than E2OVX females (51.4 +/- 4.0 pg/ml), group differences in PRL could not be attributed to E2 since OVX females, with no measurable levels of E2 (less than 15 pg/ml), had intermediate levels of PRL. These data suggest that during primate maturation serum PRL levels are dampened by some product of the ovary. Furthermore, whether age specific or environmentally mediated, this rhythm indicates an annual alteration in PRL release, with absolute levels enhanced by E2 replacement after ovariectomy, for prepubertal monkeys housed outdoors. In addition, a significant maturational increase in PRL levels was observed only in INT females when serum levels of PRL were compared for the ages 12-16 months to 24-28 months corresponding to the period between May and September for 2 successive years. These changes in PRL were not related to age-dependent changes in serum E2. Acute treatment of both E2OVX and OVX females with a single injection of E2-benzoate at three different ages did not induce any changes in serum PRL.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Generalized juvenile periodontitis, defective neutrophil chemotaxis and Bacteroides gingivalis in a 13-year-old female. A case report.

Host immune responses and the predominant subgingival microflora were evaluated in a 13-year-old female exhibiting a severe form of generalized juvenile periodontitis. The patient's neutrophils were chemotactically depressed but exhibited a normal oxidative capacity. Serum IgG antibody to Bacteroides gingivalis and to Actinobacillus actinomycetemcomitans serotype c were elevated. Significantly, B. gingivalis constituted 8 to 16% of the cultivable microflora and 13 to 20% of the total cell count in subgingival plaque samples obtained from five out of five periodontally diseased sites examined. It was not detectable in a healthy site. A. actinomycetemcomitans was recovered in small numbers from all subgingival plaque samples taken. The present study provides additional evidence for an etiologic association between B. gingivalis and generalized juvenile periodontitis.

Actinomyces↗

Oxidant-mediated electronic excitation of imipramine.

The interaction of imipramine with both resting and zymosan-activated human polymorphonuclear leukocytes (PMNs) resulted in the generation of chemiluminescence (CL). This CL was not accompanied, however, by an enhanced release of superoxide anion. CL was also observed following the interaction of imipramine with either a xanthine oxidase or a horseradish peroxidase catalyzed system. Collectively, these observations support the concept that the CL elicited from these interactions is reflective of the electronic excitation of the imipramine molecule. In contrast to the response seen with PMNs, addition of imipramine to resting alveolar macrophages (AMs) failed to yield CL. However, CL from imipramine was observed with resting AMs upon supplementation with exogenous horseradish peroxidase. The lack of response with control AMs and the significant inhibition of the imipramine-PMN CL by the myeloperoxidase inhibitor azide suggests that a peroxidase-derived oxidant facilitated the oxidation of imipramine, yielding a product in an electronically excited state. In addition to PMNs, CL was elicited from imipramine by rat or rabbit liver microsomes, suggesting that PMNs may be a useful model system to predict a xenobiotic effect on the CL response elicited by other cellular oxidant-generating systems. Moreover, these observations underscore the possibility that the metabolic activation of drugs by PMNs may be of pharmacologic and toxicologic importance.

Animals↗