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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Emerging lessons of the Interdisciplinary Generalist Curriculum (IGC) Project.

The Interdisciplinary Generalist Curriculum Project (IGC) was funded in 1993 by the Health Resources and Services Administration with the goal of developing innovative preclinical generalist curricula in ten of the nation's medical and osteopathic schools. The IGC successfully completed two competitive cycles in which ten schools were awarded three-year contracts. Although the long-term goal of the project is to increase the proportion of medical students choosing generalist careers, much has been learned thus far about the processes of curricular change and interdisciplinary cooperation. Drawing on information from school reports, site visits, external evaluations, academic presentations, and annual project meetings, this report presents the emerging lessons learned in the key areas of interdisciplinary collaboration, recruitment and retention of community preceptors, faculty development, and integration of generalist-related components into the four-year medical school curriculum. These lessons should prove useful for other schools embarking upon significant curricular innovations.

Career Choice↗
PubMed1998

Estrogen receptor-beta messenger ribonucleic acid expression in the pituitary gland.

Estrogen plays a key role in the regulation of many pituitary hormones. The presence of estrogen receptor-beta (ER beta) messenger RNA (mRNA) has been demonstrated in the adult anterior pituitary by RT-PCR to be at a level much greater than that of ER beta mRNA. Because the number of ERs has been shown to change during development, in this study we examined the distribution of pituitary ER beta mRNA in adult and prepubertal rats. Using RT-PCR, we confirmed that ER beta mRNA expression is less than that of ER alpha mRNA in adult females. In contrast, in prepubertal female pituitaries, ER beta mRNA levels are much greater than those of ER alpha mRNA. Film densitometric analysis of whole pituitaries, similarly showed that ER beta mRNA is greater in prepubertal pituitaries than in adult pituitaries. However, after emulsion autoradiography, cell counts confirmed that prepubertal and adult pituitaries differ, not in the level of ER beta mRNA expression, but in the number of cells expressing ER beta mRNA. In postnatal day 15 pituitaries, there were twice as many cells per mm2 as in adults. A comparison between prepubertal males and females showed that females exhibited a 2-fold greater level of ER beta mRNA expression. To determine which cell types express ER beta mRNA, we performed in situ hybridization for ER beta mRNA coupled with immunohistochemistry for FSH or PRL. In prepubertal pituitaries, 84.5 +/- 2.3% of FSH-immunoreactive cells also express ER beta. Nearly all of the PRL-immunoreactive cells lacked ER beta mRNA. These data demonstrate sex- and age-related differences in ER beta mRNA expression in the anterior pituitary. Furthermore, these data suggest that ER beta is not the specific mediator of estrogen action in lactotrophs, whereas ER beta may be the prime mediator of estrogen action in FSH-containing gonadotrophs.

Animals↗
PubMed1998

Effects of estradiol and exogenous insulin-like growth factor I (IGF-I) on the IGF-I axis during growth hormone inhibition and antagonism.

In adult female monkeys, serum concentrations of insulin-like growth factor I (IGF-I) are decreased by estradiol replacement, whereas levels of IGF-binding protein-3 (IGFBP-3) are increased. Furthermore, chronic IGF-I supplementation elevates serum IGFBP-3 despite a suppression of GH. To better understand how estradiol and IGF-I affect the IGF-I axis, a series of three studies was conducted to examine how estradiol and GH interact to affect the IGF-I axis and how IGF-I regulates IGFBP-1 and -3 during GH inhibition or receptor antagonism in adult female rhesus monkeys. In Exp 1, adult ovariectomized females were studied during a 28-day baseline condition and a 28-day treatment condition in which females received a constant s.c. infusion of a somatostatin analogue (octreotide, Sandoz; SSa; 6 microg/kg x day) with a 14-day washout period separating the two conditions. Within each 28-day phase, females were studied for 14 days with no estradiol replacement and for 14 days with estradiol replacement (3 microg/kg x day, s.c.). Treatment with estradiol and SSa alone significantly lowered serum IGF-I compared with baseline. In contrast, estradiol and SSa given in combination resulted in a significant increase in serum IGF-I. Serum IGFBP-3 was significantly increased by estradiol and the combination of estradiol and SSa. The response of serum GH to the acute administration of the excitatory amino acid analogue, n-methyl-D,L-aspartic acid (5 microg/kg, i.v.) was not differentially affected by any of the treatments. In Exp 2, the effects of a GH receptor antagonist (Trovert, Sensus Corp.) was assessed in ovariectomized, young adult, treated females (GHa; 1.0 mg/kg, s.c., weekly) and compared with that in untreated cohorts (Con) during 3 weeks of no estradiol and 3 weeks of estradiol replacement (3 microg/kg x day, s.c.). Serum IGF-I and IGFBP-3 were significantly suppressed in GHa compared with Con females. In Con females, estradiol replacement significantly decreased serum IGF-I and increased serum IGFBP-3. In contrast, estradiol replacement significantly elevated both serum IGF-I and IGFBP-3 in GHa females. In Exp 3, the effects of acute IGF-I administration (110 microg/kg, s.c.) were assessed during baseline conditions and during treatment with either GHa (1.0 mg/kg, s.c., weekly) or SSa (16 microg/kg, s.c. infusion) in young adult females during no estradiol replacement and during estradiol replacement (3 microg/kg x day, s.c.). Acute IGF-I administration produced a similar net increase in serum IGF-I during baseline and GHa or SSa treatment. Although serum IGFBP-3 was significantly reduced by both GHa and SSa, acute treatment with IGF-I produced a significant elevation in IGFBP-3, peaking by 3 h after treatment before returning to baseline at 7 h. Estradiol replacement elevated serum IGFBP-1 under baseline conditions as well as during GHa and SSa treatments. However, changes in serum insulin in response to the feeding patterns during the acute treatment with IGF-I, predicted changes in serum IGFBP-1. As GH secretion was inhibited during SSa, acute IGF-I had little effect on serum GH. Although acute IGF-I significantly suppressed serum GH by 3 h after treatment during baseline, the hypersecretion of GH during GHa treatment was unaffected by acute IGF-I. In conclusion, the results of the present analysis indicate that the effects of estradiol in postadolescent females on serum IGF-I are dependent on GH status, whereas estradiol consistently elevates serum IGFBP-3. Furthermore, acute IGF-I increases serum IGFBP-3 in females even during GH inhibition or receptor antagonism. Although overall serum concentrations of IGFBP-1 are elevated by estradiol and may be differentially affected by IGF-I treatment, acute changes in IGFBP-1 are more a consequence of changes in serum insulin in response to food intake. Taken together, these data suggest that IGFBP-3 is regulated by factors in addition to GH and that IGF-I can affect its own bioavailabi

Analysis of Variance↗
PubMed1998

Regulation of the growth hormone-insulin-like growth factor I axis in developing and adult monkeys is affected by estradiol replacement and supplementation with insulin-like growth factor I.

Developmental changes in the GH-insulin-like growth factor I (IGF-I) axis were evaluated in female rhesus monkeys to test the hypothesis that estradiol differentially regulates IGF-I secretion and molar ratios of IGF-I to IGF-binding protein-3 (IGFBP-3) from adolescence into adulthood and that estradiol can reestablish GH secretion in the face of enhanced IGF-I negative feedback inhibition of GH. Adult ovariectomized females were compared to ovariectomized adolescent females studied from 18-36 months of age, a period encompassing the juvenile phase through the expected age at first ovulation. A subgroup of adult (n = 5) and adolescent females (n = 5) was treated continuously with human IGF-I (110 micrograms/kg.day, s.c.) throughout the study period and were compared to age-matched, untreated adults (n = 5) and adolescent animals (n = 6). To further understand how IGF-I affects the GH-IGF-I axis, the acute response to IGF-I (100 micrograms/kg, s.c.) was assessed in adults and at two ages in developing females. Furthermore, all females were treated periodically with estradiol (4 micrograms/kg.day) to assess the effects on the parameters of the GH-IGF-I axis from adolescence into adulthood. Finally, the response to GHRH (1.0 microgram/kg, i.v.) was assessed in adult females and in adolescent females at 18 and 24 months during no estradiol and estradiol replacement. Serum IGF-I and IGFBP-3, in the absence of estradiol replacement, increased significantly throughout puberty before declining from late adolescence into adulthood. Supplementation with IGF-I resulted in a significant increase in both serum IGF-I and IGFBP-3 concentrations at all ages, although the effect was less in juvenile females. Nevertheless, the age-dependent increase and decline in IGF-I and IGFBP-3 were maintained in these supplemented animals. Estradiol replacement significantly increased both serum IGF-I and IGFBP-3 through adolescence, even in IGF-I-supplemented animals. However, with the transition from adolescence, estradiol suppressed serum IGF-I secretion, yet continued to increase IGFBP-3 in young adult and fully adult females. This change in proportionately less IGF-I compared with IGFBP-3 resulted in a significant age-dependent decrease in the molar ratio of IGF-I to IGFBP-3. Indeed, the molar ratio was highest during midadolescence, when both IGF-I and IGFBP-3 were at their zeniths. Serum IGFBP-1 was significantly higher in adolescent compared with adult females. However, estradiol replacement significantly elevated serum IGFBP-1 in adult, but not adolescent, females, abolishing the age differences observed under no estradiol conditions. Serum GH was significantly higher in adolescent compared with adult females; levels in juvenile animals were intermediate. Replacement with estradiol significantly elevated serum GH in adolescent and adult females, particularly in females supplemented with IGF-I. In contrast, estradiol had no effect on serum GH during the juvenile phase. Supplementation with IGF-I significantly dampened the response to GHRH in young and fully adult females, but not in juvenile animals. However, estradiol replacement restored the response to GHRH in these adult, IGF-I-supplemented females. These data indicate that in the absence of any ovarian influence, the decline in serum IGF-I and IGFBP-3 begins in postpubertal, young adult females and is not necessarily a consequence of old age. Furthermore, there is an age-dependent uncoupling of estradiol regulation of the GH-IGF-I axis, as estradiol stimulates GH and IGFBP-3 at all ages but increases serum IGF-I only during adolescent and decreases IGF-I in postpubertal, young adult females. Furthermore, IGF-I has a greater suppressive effect on GH secretion with advancing age, an effect reversed by estradiol replacement. These data suggest that the deficits in the GH-IGF-I axis observed in aged individuals may reflect a continuation of the regulatory changes that begin in young adult females.

Aging↗
PubMed1998

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys.

Previous data suggest that developmental increases in peripheral concentrations of insulin-like growth factor-I (IGF-I) may be one of several neuroendocrine signals that regulate the timing of puberty. In order to test this hypothesis further, normal juvenile female rhesus monkeys (Con; n = 6) were compared with age-matched animals (Igf; n = 4) which received a constant subcutaneous infusion of recombinant human IGF-I (110 micrograms/kg/day) from 18 through 36 months of age. Menstrual bleeding was monitored and ovulation was inferred from a sustained rise in serum progesterone. In order to assess the sensitivity of luteinizing hormone-releasing hormone (LHRH) neurons to excitation, the response of serum LH to the acute administration of the glutamate receptor agonist N-methyl-D, L-aspartic acid (NMDA) was assessed prior to menarche, 2 months following menarche, and during the follicular phase of a female's third ovulation or 50 days after a female's first ovulation. In addition, the pituitary response of LH secretion to an LHRH agonist was assessed during the follicular phase of a female's fourth ovulation or 75 days following her first ovulation. IGF-I treatment effectively elevated serum concentrations by more than 86% of the values observed in Con animals. Although the treatment also enhanced the developmental increase in IGF binding protein-3 (IGFBP-3), IGF-I was increased proportionately more, resulting in a significantly higher molar ratio of IGF-I:IGFBP-3 in treated females throughout the course of the study. Treatment with IGF-I did not affect age at menarche but did significantly advance the age of first ovulation. Consequently, the interval between menarche and first ovulation was significantly shorter in Igf compared with Con females. Although the total number of ovulations exhibited by Igf (3.8 +/- 0.3) and Con females (3.0 +/- 0.5) in the 12 months following menarche was similar, significantly more of these were characterized by normal luteal phase progesterone secretion in Igf (100% +/- 0) compared with Con females (64% +/- 17). An analysis of cycles with a normal luteal phase revealed that serum estradiol during the luteal phase was significantly higher in Igf compared with Con females. Finally, IGF-treated females responded to NMDA treatment with a significantly greater increase in serum LH following menarche but not prior to menarche. In contrast, the response of serum LH to an LHRH agonist did not differ between Igf and Con females. These data suggest that the premature elevation in IGF-I levels, and consequently the ratio of IGF-I:IGFBP-3, accelerates the tempo of the final stages of puberty in rhesus monkeys. This action of IGF-I is probably the result of an increase in LHRH neuronal activity and is not due to a change in pituitary sensitivity to LHRH stimulation. In addition, ovarian sensitivity to LH stimulation during the luteal phase is also increased by IGF-I. Taken together, these data suggest that developmental increases in peripheral IGF-I secretion participate in the neuroendocrine regulation of puberty in female primates.

Animals↗
PubMed1998

The impact of either a Meishan or Yorkshire uterus on Meishan or Yorkshire fetal and placental development to days 70, 90, and 110 of gestation.

Straightbred Yorkshire (Y) conceptuses are larger than straightbred Meishan (M) conceptuses throughout gestation and at farrowing. In contrast, when Y and M conceptuses were gestated together in Y recipient females, the birth weight of M pigs was similar to that of their Y littermates. Even though placentae of M pigs remained markedly smaller than placentae of Y littermates, they were significantly more vascular. The objective of this study was to compare and contrast the changes in Y and M conceptus growth and placental-endometrial vascularity throughout late gestation in Y or M uteri. Gravid uteri were recovered at slaughter from M and Y females that were gestating either M or Y conceptuses on d 70, 90, or 110 of gestation. Uterine and conceptus measurements were recorded, and a section of the intact endometrial-placental attachment site for each conceptus was fixed, embedded, and later evaluated for placental and endometrial vascular density. Placental surface area and weight were greater (P < .001) when M or Y conceptuses were recovered from Y uteri compared with M uteri on each day of gestation examined. Further, by d 110, the surface area of Y placentae was greater (P < .001) than that of M placentae, regardless of uterine type in which they were gestated. The vascular density of M placentae and adjacent endometrium doubled (P < .05) between d 70 and 110 of gestation (3.0 and 2.5 vs 6.0 and 5.1%, respectively), with no significant increase in placental surface area. In contrast, the surface area of Y placentae doubled in size (P < .001) between d 90 and 110 of gestation, but placental and adjacent endometrial vascular density remained relatively constant, averaging 3.2 and 3.8%, respectively. These data are consistent with the premise that placental size is largely determined by the uterus in which a conceptus is gestated until approximately d 90. After d 90, fetal breed-specific mechanisms maintain optimal fetal growth. Between d 90 and term, M fetal growth depends on progressive increases in placental blood vessel density and requires no increase in placental size. In contrast, Y conceptuses seem to rely exclusively on placental growth to increase placental-endometrial surface area for nutrient exchange.

Amniotic Fluid↗
PubMed1998

Results of large (8-9 mm) bilateral lateral rectus muscle recessions for exotropia.

PURPOSE: Commonly recommended maximum lateral rectus muscle recession for exotropia ranges from as little as 7 mm to as much as 11 mm. Published studies on recessions of 8 mm or more are scarce. Many ophthalmic surgeons still avoid recessions larger than 7 mm because of the fear of creating abduction deficits and surgical overcorrections. Therefore, we sought to determine the incidence of clinically detectable abduction deficits and their correlation with early surgical overcorrection in exotropic patients who had undergone large 8 to 9 mm lateral rectus muscle recessions. SUBJECTS AND METHODS: A retrospective chart review identified 30 patients with exotropia ranging from 35delta to 65delta who were treated with 8 to 9 mm recessions of both lateral rectus muscles. Patients with concurrent oblique muscle surgery were included. Mean followup time was 15 months (range 3-30 mos). RESULTS: Twenty-four patients (80%) required only one operation. The remaining 6 patients (20%) required a second operation, four for overcorrection and two for undercorrection. Nine patients (30%) had mild but persistent abduction deficits postoperatively. However, abduction deficits were not predictive of poor outcome (p=0.959). Other variables that did not significantly affect outcome included age (p=0.894), systemic anomalies (p=0.127), size of preoperative exotropia (p=0.987) and amount of rectus muscle recession (p=0.480). However, concurrent oblique muscle surgery was associated with a higher risk of a poor result. CONCLUSIONS: 8-9 mm lateral rectus recessions are not associated with a poor outcome, except in association with concurrent oblique muscle surgery.

Adolescent↗
PubMed1997

Saliva: a convenient source of DNA for analysis of bi-allelic polymorphisms of Fc gamma receptor IIA (CD32) and Fc gamma receptor IIIB (CD16).

Genetic polymorphisms of low-affinity IgG Fc receptors (Fc gamma R) have been found to influence binding of human IgG subclass antibodies, and may influence susceptibility to certain types of infectious and autoimmune diseases. Phenotypic and/or genotypic analyses of Fc gamma R polymorphisms have traditionally employed peripheral venous blood as a source of leukocytes or genomic DNA, respectively. The present study was undertaken to determine whether human salivary DNA is a suitable alternative to DNA extracted from blood for genetic analysis of FC gamma R allelic polymorphisms. Genomic DNA was extracted from whole saliva of 69 healthy adult volunteers using a commercial DNA purification kit. The average quantity of genomic DNA isolated per ml of saliva was 19.2 +/- 14.1 micrograms. To assess intrasubject variation in yield of salivary DNA, ten saliva samples were collected from a single donor over a 3-month period. The average yield of DNA recovered from these samples was 25.2 +/- 13.7 micrograms. Volumes of saliva as small as 100 microliters, as well as saliva samples stored at -70 degrees C for prolonged periods (up to 6 years), provided DNA in amounts sufficient for PCR-based genetic analysis. Two comparative PCR assays were performed using DNA extracted from both peripheral blood and saliva from a number of individuals. The assays were able to detect a single nucleotide substitution (G-->A) in the Fc gamma RIIA gene, as well as two codominant alleles encoding the NA polymorphism in Fc gamma RIIIB, respectively. Furthermore, Fc gamma RIIA and Fc gamma RIIIB genotype results were confirmed by quantitative flow cytometry using specific monoclonal antibodies. Complete concordance was achieved between the typing results of our salivary DNA, and blood DNA-based assays. Therefore, saliva appears to be an excellent source of DNA for studies of Fc gamma RIIA and Fc gamma RIIIB polymorphisms.

Adult↗
PubMed1997

Glycoprotein 46 mRNA abundance is post-transcriptionally regulated during development of Leishmania chagasi promastigotes to an infectious form.

GP46 is an abundant glycoprotein of 46 kDa on the surface of the promastigote form of most Leishmania species. We show that the steady state level of GP46 mRNA increases >>30-fold as Leishmania chagasi promastigotes develop in vitro from a less infectious form during logarithmic growth to a highly infectious form in the stationary phase of cultivation. Nuclear run-on experiments demonstrate that this increase in GP46 mRNA abundance is regulated post-transcriptionally. Plasmids containing the 3'-untranslated regions (UTRs) and downstream intergenic regions (IRs) of two different GP46 genes fused immediately downstream of the beta-galactosidase coding region were transfected into L. chagasi, and beta-galactosidase activity and mRNA levels were examined. The presence of the 3'-UTR + IR of one GP46 gene (gp46A) resulted in a steady increase in beta-galactosidase activity and mRNA level as the transfected promastigotes developed from logarithmic to stationary phase. This differential effect parallels that of the 3'-UTRs + IRs of a family of genes for an unrelated Leishmania surface glycoprotein, GP63. Thus, post-transcriptional regulation of the genes for two different surface glycoproteins of Leishmania occurs via a similar mechanism.

Amino Acid Sequence↗
PubMed1997

Lack of effect of long-term fluoride ingestion on blood chemistry and frequency of sister chromatid exchange in human lymphocytes.

Two studies were conducted to assess the potential for adverse physiologic and genotoxic effects of long-term fluoride ingestion in adults residing in three communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm). All were long-time (> or = 30 years) residents of their respective communities. Plasma and urine samples were collected for fluoride analyses. Additional plasma was collected to determine blood chemistry, and plasma lymphocytes were examined to determine the frequency of sister chromatid exchange. Significant differences in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the three communities. Seven of the blood parameters were statistically different among the communities, although all were within the defined normal range of the pathology laboratory. Sister chromatid exchange frequency was statistically higher in the 4.0 ppm fluoride community as compared to the other communities. Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second study was performed to determine if the increased frequency was potentially related to the fluoride level of the communal water supply. Of the 58 adults recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm fluoride) as their principal water source for 30 years. Data analyses showed that the sister chromatid exchange frequency did not differ between the groups, indicating that the increased sister chromatid exchange frequency was not related to the fluoride level of the communal water. The investigation provided evidence that the long-term ingestion of water containing 4.0 ppm fluoride did not have any clinically important physiologic or genotoxic effects in healthy adults.

Adult↗
PubMed1997

Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits.

We hypothesized that fluoride partly acts by changing the levels of circulating calcium-regulating hormones and skeletal growth factors. The effects of oral fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The rabbits were divided into two study groups, one control and the other receiving about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of fluoride dosing, all rabbits were euthanized and bone and blood samples were taken for analyses. Fluoride treatment increased serum and bone fluoride levels by over an order of magnitude (P < 0.001), but did not affect body weight or the following serum biochemical variables: urea, creatinine, phosphorus, total protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal fluorosis or osteomalacia was observed histologically, nor did fluoride affect serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40% (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial ash weight by 10% (P < 0.05). However, the increases in bone mass and bone formation were not reflected in improved bone strength. Fluoride decreased bone strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in fluoride-treated bones (P < 0.001), and there was a negative association between crystal width and fracture stress of the femur (P < 0.02). In conclusion, fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1 was increased by fluoride and was associated with increased bone turnover, but was not correlated with bone formation markers. High-dose fluoride treatment did not improve, but decreased, bone strength in rabbits, even in the absence of impaired mineralization.

Acid Phosphatase↗
PubMed1997

Dynamics of families during the third trimester of pregnancy in southwest Finland.

Transition to a changed family structure during pregnancy brings into focus the family's dynamics. To describe these dynamics during the third trimester of a healthy pregnancy, the Family Dynamics Measure was administered to 136 mothers and 131 fathers in southwest Finland. Mothers and fathers reported differences in 4 of the 6 dimensions of family dynamics. Clearer communication was perceived by mothers of higher social status. Second-time parents perceived greater isolation and role conflict than first-time parents. Findings contribute cues for specific family guidance by nurses during the transition to parenthood regarding partner differences, parity and social status.

Adolescent↗
PubMed1997

Immunoglobulin G subclass response to major outer membrane proteins of nontypable Haemophilus influenzae in children with acute otitis media.

Children with acute otitis media as the result of nontypable Haemophilus influenzae often develop serum bactericidal and/or opsonic IgG antibodies to this organism during convalescence. Outer membrane proteins appear to be the principal targets for such antibodies. In this study we characterized the IgG subclass responses to major outer membrane proteins of nontypable H. influenzae in otitis-prone children in whom this organism had colonized. Three of the major outer membrane proteins (P2, P5, and P6) were isolated from the homologous nontypable H. influenzae strain recovered from the middle ear at the time of acute infection. Sera were obtained during the acute phase and at 1 and 6 months thereafter. The outer membrane proteins, which were isolated by preparative sodium dodecylsulfate-polyacrylamide gel electrophoresis, were used as test antigens in a quantitative IgG subclass enzyme immunoassay. The results of this analysis indicate that the temporal characteristics and distribution of IgG subclass antibodies were found to differ for each of the outer membrane proteins. Moreover, substantial variation between patients was observed with respect to both temporal characteristics and subclass distribution of the IgG response to the three outer membrane proteins. Significantly, sera from two of three otitis-prone subjects contained detectable levels of IgG antibody to the conserved P6 outer membrane protein at the time of acute infection, with serum from one subject also containing detectable levels of IgG3 antibody to this same protein. Nevertheless, the organism persisted in the middle ears of these patients. The results of this study indicate that otitis-prone children manifest a highly variable IgG subclass response to both conserved (P6) and variable (P2) outer membrane proteins of nontypable H. influenzae. Further study is required to ascertain whether these IgG subclass antibodies are biologically efficacious and whether otitis-prone children possess the immunologic maturity to respond to nontypable H. influenzae outer membrane protein-based vaccines in a predictable manner.

Acute Disease↗
PubMed1997

Combined bilateral superior rectus muscle recession and inferior oblique muscle weakening for dissociated vertical deviation.

PURPOSE: Dissociated vertical deviation (DVD) is a common disorder that is often difficult to treat satisfactorily with extraocular muscle surgery. Weakening both elevators in a single eye is uncommonly performed because of possible severe upgaze deficiency or chin-up head posture postoperatively. METHODS: A retrospective review of medical records was performed that yielded 14 patients who had undergone bilateral superior rectus muscle recessions (mean 8.1 mm, range 5-10 mm) and bilateral inferior oblique muscle recession, myectomy, or anterior transposition in the treatment of DVD. Three additional patients with asymmetric inferior oblique muscle overaction or true hypertropia in primary gaze position were identified who had bilateral superior rectus muscle recessions combined with unilateral inferior oblique muscle weakening. RESULTS: Mild-to-moderate elevation deficiencies were common postoperatively but never exceeded -2 up-gaze limitation (scale 0 to -4) except in the immediate postoperative period and were not associated with persistent chin-up head posturing. Cosmetically objectionable upper eyelid retraction occurred in one patient after re-recession of a superior rectus muscle but before inferior oblique muscle surgery. Only three patients undergoing four vertical muscle surgeries had residual DVD >10 PD in primary gaze position, and none exhibited manifest dissociated strabismus warranting further treatment. CONCLUSION: Bilateral superior rectus muscle recession of up to 10 mm combined with inferior oblique muscle weakening appears to be a safe surgical approach in the management of patients with large angle or recurrent DVD. Our data further suggest that simultaneous four vertical muscle surgery may be preferred in some patients to weakening the superior rectus or inferior oblique muscles alone.

Depth Perception↗
PubMed1997

Differences in trophectoderm mitotic rate and P450 17alpha-hydroxylase expression between late preimplantation Meishan and Yorkshire conceptuses.

We have previously demonstrated that Meishan preimplantation conceptuses contain fewer cells and produce less estradiol-17beta (E2) than do Yorkshire conceptuses on the same day after ovulation. We have also shown that the apparent rate-limiting enzyme for biosynthesis of E2, P450 17alpha-hydroxylase/17-20 lyase (P450c17), is maximal on Day 11.5 of gestation in both Meishan and Yorkshire conceptuses, with the level of enzyme expression being significantly greater in Yorkshire as compared to Meishan conceptuses. Other authors have suggested that insulin-like growth factor-I (IGF-I) from the pig endometrium is stimulated by conceptus E2 that may function to stimulate additional conceptus steroidogenic enzyme activity. In order to better understand developmental differences between these two breeds, conceptuses 2, 4, 6, and 8 mm in diameter were collected and fixed in 10% neutral buffered formalin. Uterine flushings associated with these conceptuses were used for quantification of E2 and IGF-I. Techniques were developed in processing the fixed conceptuses so as to eliminate excessive convolutions of the trophectoderm. Conceptuses could then be embedded in paraffin in an "inflated" state, which allowed orientation of the conceptus with respect to the embryonic disk. Sections of these conceptuses were then immunocytochemically stained for proliferating cell nuclear antigen (PCNA) and P450c17. At all sizes examined, Meishan conceptuses exhibited a reduced trophectoderm mitotic rate when compared to Yorkshire conceptuses as measured by PCNA immunostaining. Meishan conceptuses were first observed to stain positively for P450c17 at a diameter of 4 mm, whereas Yorkshire conceptuses were first observed to stain positively for P450c17 when they had reached a diameter of 6 mm. E2 in the uterine flushings from both breeds was low and similar if the average littermate conceptus diameter was 2 or 4 mm, but was markedly increased in association with litters of 6- or 8-mm conceptuses, with E2 in flushings from Yorkshire females increasing more than Meishan females. The concentration of IGF-I was consistently elevated in flushings from Yorkshire as compared to Meishan females. Embryonic E2 production is thought to influence conceptus survival; therefore, the reduced trophectoderm mitotic rate and/or uterine luminal IGF-I concentration of the Meishan, as compared to Yorkshire, may limit E2 synthesis--a limitation that could lead to decreased conceptus mortality in this breed.

Animals↗
PubMed1997

Ontogeny of gene expression in the gonadotroph of the developing female rat.

During the infantile period of the female rat (8-21 postnatal days [PND] of age), there is a dramatic increase in plasma FSH, which is thought to be important in initiating ovarian activity and, perhaps, the onset of puberty. To begin to understand the regulation of this FSH surge, we determined the ontogenetic development of LHbeta, FSHbeta, and GnRH receptor (GnRH-R) mRNA levels in the pituitary gland throughout the infantile period of the female rat. Steady-state mRNA levels were determined by an external standard quantitative reverse transcriptase polymerase chain reaction assay. FSHbeta and GnRH-R mRNA levels increased to peak on PND 12 (p < 0.03). LHbeta mRNA levels remained relatively constant until rising on PND 18. A GnRH antagonist (10-100 microg/animal) was administered daily from PND 8-11 or PND 11-13, and animals were killed on PND 12 or PND 14, respectively. FSHbeta, LHbeta, and GnRH-R mRNAs were not affected by GnRH antagonist treatment. Plasma FSH was selectively reduced in the first group, whereas both plasma LH and FSH were suppressed in the second group. These data indicate that gene expression of LHbeta, FSHbeta, and GnRH-R are differentially regulated in the infantile female rat pituitary. GnRH is involved in regulating the secretion of FSH and LH during the infantile period but not in regulating FSHbeta, LHbeta, or GnRH-R mRNA gene expression.

Aging↗
PubMed1997

Opsonization of Actinobacillus actinomycetemcomitans by immunoglobulin G antibodies to the O polysaccharide of lipopolysaccharide.

Sera of localized juvenile periodontitis (LJP) patients colonized by Actinobacillus actinomycetemcomitans serotype b often contain markedly elevated levels of immunoglobulin G (IgG) antibodies to serospecific determinants in the O polysaccharide of lipopolysaccharide (LPS), as well as to outer membrane proteins of this species. IgG antibodies in LJP sera are known to opsonize A. actinomycetemcomitans for subsequent phagocytosis and killing by human neutrophils. The objective of this study was to determine whether outer membrane proteins or serospecific determinants in LPS are the primary target for opsonic IgG antibodies in LJP sera. An A. actinomycetemcomitans serotype b O-polysaccharide affinity column was constructed and subsequently used to purify LPS-specific IgG antibodies from LJP serum. The affinity-purified anti-LPS IgG antibodies were enriched in content of IgG2 (66.2%, compared with 37.0% in the total IgG fraction) and were immunospecific for A. actinomycetemcomitans serotype b LPS. In an opsonophagocytic assay using neutrophils from donors who were homozygous for the H131 allotype of Fcy receptor IIa (CD32), it was found that LPS-specific IgG antibodies exhibited substantially greater opsonic activity toward A. actinomycetemcomitans serotype b than an LJP IgG fraction that was depleted of LPS-reactive antibodies but contained antibodies against outer membrane proteins of this species. The results of this study indicate that serospecific determinants in the O polysaccharide of A. actinomycetemcomitans serotype b are a principal target for opsonic antibodies in sera of LJP subjects.

Aggregatibacter actinomycetemcomitans↗