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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 289 records · Page 16Linked to original sources

Primary inferior oblique overaction in congenital esotropia, accommodative esotropia, and intermittent exotropia.

A statistical analysis of the onset and natural history of primary inferior oblique eye muscle overaction (IOOA) was conducted using the records of 456 strabismus patients. With 5 years or more of follow-up, IOOA developed in 72% of congenital esotropes (CETs), 34% of accommodative esotropes (AETs), and 32% of intermittent exotropes (X[T]s) at an average age of 3.6, 5.2, and 5.2 years, respectively. Incidence of IOOA was positively related to the number of horizontal surgeries in CETs but not in AETs or X(T)s. Incidence was not related to age of onset of strabismus, time from onset of strabismus to surgery, age at first surgery, or decompensation of ocular alignment. Mild IOOA did revert to normal in 12 patients after only horizontal surgery. The association of IOOA with dissociated vertical deviation, as well as symmetry, range of age of detection, and recurrence after surgery are also explored.

Accommodation, Ocular↗

Conservative management of childhood orbital lymphangioma.

Repeated partial excisions are commonly performed for orbital lymphangiomas. Even with the advent of carbon dioxide (CO2) laser as an adjunct to subtotal excision, surgical complications remain common. The authors report six cases of childhood orbital lymphangioma, biopsy proven in five, in which conservative management of recurrent hemorrhage without additional surgery resulted in subsidence of proptosis and return of 20/20 visual acuity. Surgical aggressiveness for recurrent hemorrhages must be tempered by the knowledge that normal vision often results from cautious observation alone.

Bed Rest↗

Opsonic IgG antibody against Actinobacillus actinomycetemcomitans in localized juvenile periodontitis.

Actinobacillus actinomycetemcomitans is a gram-negative bacterium frequently recovered from periodontal lesions of patients with localized juvenile periodontitis (LJP). Elevated levels of serum IgG and IgM antibodies to A. actinomycetemcomitans antigens are frequently observed in LJP patients, although the functional properties of such antibodies have not been characterized systematically. In this study, we analyzed serum from LJP subjects infected with A. actinomycetemcomitans with respect to the presence of IgG antibodies expressing opsonic, bactericidal and/or leukotoxin-neutralizing activity against this organism. The IgG fractions obtained from serum of 3 LJP patients with elevated antibody titers to A. actinomycetemcomitans contained opsonic activity against a non-leukotoxic Y4 strain, as well as for a highly leukotoxic JP2 strain. Opsonic activity required the presence of complement. The IgG fractions of pooled normal serum and serum from a fourth LJP subject with minimal ELISA-reactive IgG antibody against this organism lacked detectable opsonic activity. Leukotoxin-neutralizing IgG antibodies, although variably present, did not influence neutrophil killing of the leukotoxic JP2 strain. None of the sera tested contained bactericidal IgG antibodies capable of promoting direct complement-mediated killing of A. actinomycetemcomitans. These results indicate that LJP subjects infected with A. actinomycetemcomitans are capable of producing opsonic IgG antibodies which may facilitate neutrophil-mediated host defense against this periodontopathic organism.

Actinobacillus↗

Sexuality in children and adolescents with cancer: pediatric oncology nurses' attitudes and behaviors.

It is essential that health professionals openly discuss how cancer may affect the developing sexuality of childhood cancer patients. This study was conducted to explore nurses' attitudes and behaviors regarding sexuality in cancer patients. Results are reported for a subset of a larger study (N = 937) from subjects who indicated that their practice included children and/or adolescents (N = 156). The Williams-Wilson Sexuality Survey was used to measure attitudes towards sexuality in cancer patients, behavior in nursing care related to the sexuality of a cancer patient, and attitudes towards sexuality in the child and/or adolescent with cancer. The majority of subjects agreed that sexuality should be a routine component of nursing care, yet less than half had actually discussed an alternation in sexuality with an adolescent patient. More than one third said they were not comfortable in initiating such discussions. However, they were comfortable in discussing sexuality concerns when these discussions were initiated by the patient and/or family.

Adolescent↗

Effects of growth hormone on the tempo of sexual maturation in female rhesus monkeys.

The signal that initiates and maintains the developmental change in LHRH and, consequently, LH secretion in primates, thus regulating the tempo of puberty, is not known. Given the close association between reproductive development and bone maturation, we examined the hypothesis that GH was involved in developmental increases in LH release, specifically by augmenting the decrease in estradiol (E2) negative feedback inhibition of LH that characterizes late puberty in primates. Recombinant human GH (rhGH; 250 micrograms/kg) was given (sc) three times weekly to immature female rhesus monkeys to determine if developmental increases in basal serum LH would occur at an earlier age, and if menarche and first ovulation also would be advanced. The study groups included intact females receiving rhGH (INT + GH; n = 5), intact control animals (INT; n = 6), ovariectomized females receiving E2 plus rhGH (E2OVX + GH; n = 5), and E2-treated ovariectomized control monkeys (E2OVX; n = 4). The females were studied from 20 months of age until their serum LH levels increased (E2OVX groups) or until the occurrence of first ovulation (intact groups). After 12 months of rhGH treatment, the crown-rump lengths were significantly increased, regardless of ovarian status, an effect maintained in the intact females through 21 months of treatment. The mean age at the time of the initial rise in serum LH was advanced by rhGH treatment in intact females (29.6 +/- 0.4 vs. 31.3 +/- 0.3 months), but not E2OVX females. Subsequent maturational elevations in LH secretion were similar in the E2OVS + GH and E2OVX animals even after an incremental increase in E2. Ages at menarche were similar in the INT + GH and INT groups, whereas first ovulation was significantly advanced in three of five INT + GH females (31.5 +/- 0.7 months) compared to that in INT females (43.5 +/- 0.3 months). The remaining INT + GH females ovulated at an age (42.4 +/- 0.4 months) similar to that of INT females. Those females that ovulated by 32 months had higher skeletal maturity scores than the later ovulating INT females, with the other INT + GH females being intermediate. Furthermore, rhGH resulted in a significant increase in serum E2 levels within 12 h of injection, which remained elevated through 24 h. This effect of rhGH on ovarian E2 secretion did not occur until females had shown elevations in basal serum LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Season determines timing of first ovulation in rhesus monkeys (Macaca mulatta) housed outdoors.

In order to determine the relative importance of age and season on the occurrence of first ovulation in rhesus monkeys, the timing of puberty in spring-born females (Group S, N = 13) was compared to that of fall (N = 3) and winter-born (N = 5) females (Group W). All females were housed outdoors and were studied from 12 months of age through first ovulation. Menarche occurred at a similar age but significantly earlier in the year for Group W (31.2 +/- 0.7 months; 25 August +/- 19.5 days) than for Group S females (31.2 +/- 0.7 months; 14 November +/- 17.1 days). First ovulation, as assessed from twice weekly serum progesterone determinations, occurred exclusively in the fall or winter in a bimodal age distribution for all females. For Group W females, 6/8 ovulated during the 3rd year at 35.8 +/- 0.7 months while 2/8 ovulated during the 4th year at 45.3 +/- 0.1 months. In contrast, only 3/13 Group S females ovulated during the 3rd year and at a significantly younger age of 31.4 +/- 0.4 months compared to Group W. The remaining Group S females (10/13) ovulated the following autumn at 43.2 +/- 0.2 months, significantly younger than the later ovulating Group W females. In addition to this pattern of first ovulation, serum concentrations of prolactin varied seasonally, rather than with age, in both groups of females with higher levels in the summer and low levels in the winter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗

Short-day melatonin pattern advances puberty in seasonally breeding rhesus monkeys (Macaca mulatta).

Prepubertal, spring-born females (Group H: N = 5) living outdoors were given a daily injection of melatonin (0.70 microgram/kg, s.c.) late in the afternoon to produce a short-day melatonin pattern equivalent to a night of approximately 14 h. The dose of melatonin produced serum concentrations of melatonin which simply extended, within the 24 h day, the normal endogenous nighttime elevation (80-100 pg/ml). The study was started in March when the females were 23 months of age and continued through January. Parameters of sexual maturation for this group were compared to those of untreated, age-matched females (Group C: N = 5) which also lived outdoors under changing environmental conditions. Melatonin treatment significantly advanced age at first perineal swelling (23.9 +/- 0.5 vs 30.5 +/- 0.2 months) and menarche (26.2 +/- 0.9 vs 31.2 +/- 2.4 months). Since all of the females were spring-born, these events occurred earlier in the year in Group H females (swelling: April vs October; menarche: June vs November). Furthermore, 4/5 Group H females exhibited first ovulation in December at 31.8 +/- 0.3 months. None of the Group C females ovulated during their 2nd year, but all did so the next breeding season at 43.5 +/- 0.3 months. All first ovulations in females had luteal-phase progesterone concentrations elevated for at least 12 days with peaks greater than 3.0 ng/ml. Body weights were similar between groups until the post-menarchial interval when weight gain was greater in the melatonin-treated females. A similar pattern of group differences also was observed for serum concentrations of growth hormone and somatomedin-C. In addition, prolactin concentrations were seasonally elevated during the summer months in both groups, but concentrations fell to nadir values by August in Group H females and remained elevated until October in Group C animals. These results suggest that, in adolescent females housed outdoors, exposure to a short-day melatonin pattern permits sexual maturation to be initiated at an earlier age, allowing first ovulation to occur in the months immediately after menarche. A long-day melatonin pattern, typically experienced by females at this developmental age, may actually delay the initiation of maturational events until the subsequent fall months.

Animals↗

Nocturnal changes in serum melatonin during female puberty in rhesus monkeys: a longitudinal study.

Diurnal concentrations of serum melatonin were determined longitudinally in female rhesus monkeys throughout sexual maturation to ascertain how levels varied with advancing age and reproductive onset. Females were housed either in outdoor enclosures (n = 8) exposed to ambient environmental conditions, or indoors (n = 4) under a photoperiod of 12 h light: 12 h darkness and fixed temperature of 20-23 degrees C. Animals were studied from immaturity (15 months) through first ovulation and were additionally compared with fully adult female rhesus monkeys (n = 5) studied during the annual breeding season. The diurnal melatonin pattern was described for the developing females in the summer, autumn and winter in 3 successive years from samples collected at 10.00, 18.00, 22.00, 02.00, 06.00 and 10.00 h. Nocturnal levels of melatonin declined significantly during development in both indoor- and outdoor-housed females with a progressive decrease up to 33 months of age. Daytime values were consistently low but exhibited a slight decline also with age. Nocturnal values in all months sampled fell significantly with greater decreases occurring at the earliest ages. Furthermore, superimposed upon this developmental change, animals housed outdoors responded to seasonal changes in photoperiod with diurnal increases in melatonin occurring after sunset. The females in the present study exhibited first ovulation at two distinct ages: 32-37 months ('early', n = 6) and 41-45 months ('later', n = 5). One female did not ovulate within the study period. Although nocturnal levels of serum melatonin were similar between the two groups up to 29 months of age, a post-hoc analysis revealed that concentrations were significantly lower by 34 months of age for the early group, a time coincident with first ovulation. Nocturnal levels of melatonin remained high, relative to the early group, in the later ovulating females until 43 months of age, coincident with first ovulation for these animals. The diurnal pattern of serum melatonin at first ovulation, regardless of chronological age, was similar to that observed during the ovulatory season for adult female rhesus monkeys. These data suggest that nocturnal melatonin concentrations decline with advancing chronological age in prepubertal female rhesus monkeys.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Does a residents' continuity clinic provide primary care?

Pediatric residents are required to care for a group of children over a period of time. For many, this "continuity" experience is in a hospital outpatient department that may or may not provide primary care. We applied a measure of primary care to the Primary Care Clinic, the continuity clinic at The Johns Hopkins Hospital, Baltimore, Md, and found that it compared favorably with private pediatric practices in the Baltimore area, providing significantly more "principal care" (93% vs. 84.5% of encounters), and to the Harris Lane Home walk-in clinic, where only 51% of encounters were "principal care". The Primary Care Clinic scored higher on a primary care index, a measure of the extent to which the facility serves as a primary care source for patients, suggesting that hospital-based training can provide residents with an opportunity to provide primary care.

Child↗

The major concanavalin A-binding surface glycoprotein of Leishmania donovani chagasi promastigotes is involved in attachment to human macrophages.

Leishmania donovani, the protozoan causing visceral leishmaniasis, is an obligate intracellular parasite of mammalian macrophages. Considerable evidence has suggested that the ingestion of L. donovani promastigotes by macrophages occurs via receptors on the surface of the phagocyte. During this study, a glycoconjugate that may be involved in the receptor-mediated ingestion of L. donovani chagasi promastigotes was isolated from the parasite membrane. Octyl glucoside-soluble extracts of promastigote membranes contained a predominant doublet migrating at 60 kDa, seen by SDS-PAGE. The 60-kDa molecule was the major externally disposed promastigote surface protein labeled by 125I, and it was the major Con A-binding protein on L. donovani chagasi, as determined by Con A binding to parasite proteins transferred to nitrocellulose. Attachment of promastigotes to human monocyte-derived macrophages was inhibited by varying concentrations of the membrane extract containing both proteins, and adsorption of extracts on Con A-Sepharose resulted in both removal of the 60,000 Mr glycoprotein and loss of the ability of extracts to inhibit promastigote attachment to human macrophages. After further purification of the 60-kDa glycoprotein by gel filtration, its inhibitory activity increased 45-fold over the unpurified membrane extract. Examination of Con A blots of stationary phase promastigotes isolated from an infected hamster revealed a marked loss in the major Con A-binding glycoprotein over 4 mo in in vitro culture after isolation from the rodent host, corresponding to a loss in infectivity of the promastigotes for hamsters. The results suggest that the major Con A-binding surface glycoprotein from L. donovani chagasi promastigotes is important in attachment to human macrophages, and may be a factor in parasite virulence for a mammalian host.

Animals↗

Dietary influences on growth and sexual maturation in premenarchial rhesus monkeys.

The effect of a high-fat diet on growth, sexual maturation, and developmental changes in serum levels of estradiol (E2), growth hormone (GH), somatomedin-C (Sm-C), and insulin were examined in outdoor-housed premenarchial rhesus monkeys. From 16 to 32 months of age, females were fed either a high-fat diet (HFD, N = 5) with 31% calories from fat or a control diet (commercial laboratory chow, N = 10) with 12% of the calories from fat. Maintenance on a HFD did not accelerate physical growth, as all animals exhibited similar increments in body weight, crown-rump length, and weight/height ratios. In contrast, the HFD group exhibited an earlier onset of perineal swelling and menarche despite lower body weights during that time. Moreover, 80% of the HFD animals exhibited an early first ovulation (31-32 months of age) compared with 40% of control animals. These reproductive changes were associated with significant differences in the endocrine profiles of HFD animals. Fasting serum levels of insulin were significantly elevated within 2 months of diet treatment and remained elevated throughout the study period. Levels of Sm-C were elevated relative to those of controls after 3 months of diet treatment, but not thereafter. Serum GH increased after 6 months on the HFD and, overall, concentrations were higher in HFD animals. A significant rise in E2 was observed after only 45 days on the HFD treatment. These concentrations did not differ from 18 to 21 months of age but again were elevated at 27 months in the HFD females. Since these endocrine and physical changes associated with reproductive physiology occurred in the absence of enhanced growth, these data suggest that a high-fat diet may influence the rate of sexual maturation through changes in certain metabolic factors which may act on the developing neuroendocrine system.

Animals↗

Association of Autographa californica nuclear polyhedrosis virus (AcMNPV) with the nuclear matrix.

Nuclear matrices from uninfected Spodoptera frugiperda cells and those infected with Autographa californica nuclear polyhedrosis virus (AcMNPV) were isolated and their protein constituents were compared. Proteins were characterized according to size and several different antibodies to Drosophila nuclear proteins were employed in an attempt to identify the proteins comprising this nuclear substructure. Three species of lamins were identified as major constituents of the nuclear matrix of Spodoptera cells. Two DNA-binding proteins having molecular weights of 54 and 36 kDa were also identified as components of the nuclear matrix of uninfected cells. Infection resulted in a superimposition of viral proteins upon the nuclear matrix of the host cell. Polyhedrin, the basic viral DNA-binding protein (p6.9), and the major capsid protein of AcMNPV were identified immunologically as components of the nuclear matrix fraction of infected cells. Infection also resulted in the increased association of cellular histones with the nuclear matrix. DNA-binding assays demonstrated histones and p6.9 were the predominant DNA-binding proteins associated with the nuclear matrix of infected cells. Nuclear matrices from uninfected cells and cells infected with AcMNPV for 10 and 24 hr were examined using transmission electron microscopy. Morphologically, the nuclear matrix of the uninfected cell consists of the outer nuclear lamina (including nuclear pore complexes), an internal fibrogranular protein constituent, and a residual nucleolar structure. Numerous viral capsids were observed associated with the nuclear matrix in cells infected with either wild-type AcMNPV or a polyhedrin-deletion mutant by 10 hr p.i. The capsids appeared to be attached in an end-on association with the internal fibrogranular protein network of the nuclear matrix. The matrix-associated capsids were similar in width and length to those packaged within the polyhedra. In addition to the capsids, polyhedra in various stages of maturation were seen at 24 hr following infection of the cells with the wild-type virus. The nuclear matrix of the infected cell appears to play an important role in baculovirus assembly.

Animals↗

A synthetic peptide to the predicted 6.9K translation product of the HindIII-H/EcoRI-D region of the AcNPV genome induces antibodies to the basic DNA-binding protein.

The sequence of the HindIII-H/EcoRI-D region of the AcNPV genome revealed a 55 codon methionine-initiated open reading frame (Wilson, M.E., Mainprize, T.H., Friesen, P.D. and Miller, L.K., 1987, J. Virol. 61, 661-666). This open reading frame predicts a 6.9K translation product with an amino acid composition nearly identical to the basic virion DNA-binding protein. A synthetic peptide was prepared to a region of the predicted 6.9K protein and used to induce antibodies in rabbits. Western blots of viral proteins, infected cell-specific proteins (24 h p.i.), and basic chromatin-associated proteins (24 h p.i.) were probed with anti-6.9K antisera. In all immunoblots, the anti-6.9K antisera were specific for the basic DNA-binding protein. This investigation provides further evidence that the basic DNA-binding protein of the virion is a viral-encoded gene transcribed from the HindIII-H/EcoRI-D region of the genome.

Animals↗

Predicting difficult intubation.

The amount of larynx seen at intubation was assessed in 633 adult patients undergoing routine surgery. Various measurements of the head and neck were made in an attempt to discover which features were associated with difficulty with laryngoscopy (defined as the inability to see even the arytenoids). In addition 38 patients, reported by colleagues because they had been "difficult to intubate", were measured. Five useful risk factors, measured at three levels of severity, were identified. A simple predictive rule was developed and tested on a prospective set of 778 patients, in 1.5% of whom laryngoscopy was found to be difficult. Depending on the threshold chosen, the rule allowed the detection of, for example, 75% of the "difficult" laryngoscopies at a cost of falsely identifying 12% of the "not difficult" patients.

Adult↗

Prolonged lactational infertility in adolescent rhesus monkeys.

The present study examined the effects of first pregnancy and nursing behavior on postpartum infertility in seasonally breeding rhesus monkeys to assess whether prolonged lactational infertility observed in adolescent mothers is due to a particular pattern of nursing or to decrements in body growth rates. After a successful first pregnancy, a significant percentage of the lactating adolescent mothers (57.1%; n = 8) failed to exhibit an ovulation with normal luteal phase during the subsequent breeding season. In contrast, the remaining lactating adolescents (42.9%, n = 6) and all of the adult mothers (100%, n = 6) exhibited ovulations with a normal luteal phase. Age alone was not the critical variable, since all nonlactating adolescents exhibited ovulations with normal luteal phase parameters in the subsequent breeding season. The luteal phase abnormalities exhibited by the subset of lactating adolescent females were characterized by an inadequate luteal phase (ILP) and by significantly lower serum levels of progesterone, estradiol, and bioactive luteinizing hormone. The occurrence of these ILP ovulations was associated with more frequent nursing bouts prior to ovulation and during the subsequent luteal phase. In contrast, nursing patterns for adult females who had ovulations with normal luteal phases were more similar to those of the infertile lactating adolescents exhibiting significantly longer and more frequent nursing bouts, suggesting that fully adult females may be less sensitive to the inhibitory aspects of a suckling stimulus. Differences in luteal phase function among lactating adolescents were not related to differential rates of ponderal or skeletal growth. A still-developing neuroendocrine system may thus render a significant proportion of adolescent females more sensitive to suckling-induced suppression of gonadotropin secretion.

Animals↗

Effect of clindamycin on neutrophil killing of gram-negative periodontal bacteria.

Periodontal diseases are infections of the tissues supporting the dentition. Recognition that relatively specific microfloras are associated with distinct clinical forms of periodontal disease has prompted the use of antimicrobial agents as adjuncts in periodontal therapy. Clindamycin is one of several antibiotics known to concentrate in bioactive form in neutrophils and to potentiate phagocyte bactericidal activity against certain bacteria. Neutrophils appear to play a key role in host defense against periodontopathic gram-negative bacteria. In the present study, we evaluated the effect of preincubation of neutrophils with therapeutically achievable concentrations of clindamycin upon subsequent in vitro bactericidal activity against three species of gram-negative periodontal bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga ochracea. In each instance, clindamycin neither enhanced nor inhibited the kinetics of bactericidal activity at low bacterium-neutrophil multiplicities. Further, this antibiotic had no demonstrable effect upon neutrophil bactericidal capacity, as assessed at bacterium-neutrophil ratios as high as 50:1. Our results indicate that clindamycin does not potentiate neutrophil bactericidal activity against the species of gram-negative periodontal organisms tested.

Actinobacillus↗

Roles of CR3 and mannose receptors in the attachment and ingestion of Leishmania donovani by human mononuclear phagocytes.

Leishmania donovani is an obligate intracellular parasite of mammalian macrophages. Two macrophage receptors, the mannose-fucose receptor (MFR) and the receptor for complement component C3bi, CR3, were examined for their roles in the attachment and ingestion of L. donovani by human monocyte-derived macrophages. Two monoclonal antibodies which bind to the human CR3, anti-Mo1 and anti-Mac-1, inhibited both attachment and ingestion of L. donovani promastigotes after preincubation with human monocyte-derived macrophages; attachment was inhibited by 40 and 62% by anti-Mo1 and anti-Mac-1, respectively, and ingestion was inhibited by 34 and 51% by anti-Mo1 and anti-Mac-1, respectively. The interaction between promastigotes and CR3 may not have involved the C3bi-binding site on CR3, however, because a monoclonal antibody which exhibits specificity for this site, OKM10, inhibited promastigote attachment by only 18%. In contrast, OKM1, which is believed to react with the alternate lectinlike binding site on CR3, inhibited ingestion by 65%. MFR activity was inhibited using the soluble MFR ligands, mannan and mannosylated bovine serum albumin, which also inhibited promastigote attachment by 40 and 37%, respectively. The simultaneous inhibition of both CR3 (by anti-Mac-1) and the MFR (by either mannan or mannosylated bovine serum albumin) resulted in a greater decrease in promastigote attachment than inhibition of either receptor alone. Additionally, the reduction of MFR activity by allowing macrophages to adhere to a mannan-coated surface followed by the addition of anti-CR3 antibodies resulted in an 81% inhibition of promastigote ingestion, a greater decrease than was obtained by manipulation of either receptor alone. The results suggest that the MFR and CR3 independently participate in the attachment and ingestion of L. donovani promastigotes by human macrophages.

Animals↗