Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 109 records · Page 6Linked to original sources

PubMed1998

The importance of TGF-beta in murine visceral leishmaniasis.

IFN-gamma is critical for the cure of leishmaniasis in humans and mice. BALB/c mice are genetically susceptible to infection with the visceralizing species of Leishmania, L. chagasi. We have evidence that a soluble factor(s) inhibits IFN-gamma production by cultured liver granuloma cells from BALB/c mice during L. chagasi infection. In contrast, liver granulomas from C3H.HeJ mice, which are genetically resistant to L. chagasi infection, produce abundant IFN-gamma. According to ELISAs and neutralization studies, there was not evidence that the Th2-type cytokines IL-10 or IL-4 contributed to IFN-gamma suppression. However, both Ab neutralization and immunohistochemistry showed that granuloma-derived TGF-beta was, at least in part, responsible for inhibiting IFN-gamma release by CD4+ cells in BALB/c liver granuloma cultures. Consistently, TGF-beta levels were high in liver granulomas from susceptible BALB/c mice but low in resistant C3H mice or in BALB/c mice that were immunized against L. chagasi disease. Administration of recombinant adenovirus expressing TGF-beta (AdV-TGFbeta) but not IL-10 (AdV-IL10) caused genetically resistant C3H mice to become significantly more susceptible to L. chagasi infection. In contrast, either AdV-TGFbeta or AdV-IL10 could abrogate the protective immune response achieved by immunization of BALB/c mice. We conclude that locally secreted TGF-beta inhibits Th1-associated cure of murine visceral leishmaniasis caused by L. chagasi, independently of Th2-type cytokines.

Adenoviridae↗

PubMed1998

Regulatory sequences and a novel gene in the msp (GP63) gene cluster of Leishmania chagasi.

The surface protease GP63 of Leishmania chagasi is encoded by a cluster of more than 18 tandem major surface protease (msp) genes belonging to three classes (mspL, mspS, mspC). mspL and mspS transcripts are differentially expressed during parasite growth. RNAs from mspS genes predominate during stationary phase, the time when parasite virulence and GP63 expression are maximal. We hypothesized that the unique regions downstream of mspS genes contain signals important for gene expression. The 2.8 kb region between tandem mspS genes was found to contain an 882 bp open reading frame designated mag. Copies of mag were found downstream of all mspS genes in the cluster. mag hybridized faintly to bands on Northern blots and a fully processed mag cDNA was identified in a promastigote cDNA library, providing evidence that mag genes are expressed at low levels. Similar to mspS RNAs, the abundance of mag RNAs was greater in stationary phase than logarithmic phase organisms, although mag RNAs were less abundant than mspS RNAs throughout growth. Northern blots and enzyme assays of promastigotes containing plasmid constructs in which the beta-galactosidase gene was followed by sequences between mspS coding regions, either with or without mag and its downstream sequences, suggest these regions have several regulatory effects accounting for the growth-associated changes in mspS expression.

3' Untranslated Regions↗

PubMed1998

Timing of initial screening examinations for retinopathy of prematurity.

OBJECTIVE: To test a screening protocol for retinopathy of prematurity (ROP) that uses the dual criteria of postconceptional age and chronological age, rather than a single parameter, to determine precisely when to begin eye examinations. METHODS: We retrospectively reviewed medical records of 179 infants (326 eyes) who had undergone laser treatment for threshold ROP. We entered their chronological and postconceptional ages at treatment into a database and evaluated various screening parameters to determine the combination of criteria that would allow us to safely postpone the initial eye examinations. RESULTS: Screening infants at 7 weeks of chronological age or 34 weeks of postconceptional age (whichever comes first), but not before 5 weeks of chronological age, seems to reliably detect the onset of threshold ROP while reducing the number of unnecessary early examinations. CONCLUSION: Simultaneously applied dual criteria of chronological age and postconceptional age may be a superior method of determining when to initiate ROP examinations and is preferable to using either chronological age or postconceptional age alone.

Age of Onset↗

PubMed1998

Keeping quiet.

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Humans↗

PubMed1998

Dose-response to a two-component acellular pertussis vaccine in infants and comparison with whole-cell vaccine.

In an effort to determine the optimal dose of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) for use in acellular pertussis vaccines we compared the immunogenicity and safety of acellular pertussis vaccine combined with diphtheria and tetanus toxoids containing 12.5 microg (DTaP-12.5) or 25 microg (DTaP-25) each of PT and FHA with a whole cell pertussis vaccine in infants immunized at 2, 4 and 6 months of age. Recipients of acellular vaccines developed higher anti-FHA concentrations and more rapid anti-PT serological responses that infants who received whole cell pertussis vaccine combined with diphtheria and tetanus toxoids (DPT). A dose response was noted; infants immunized with DTaP-25 developed significantly (P<0.03) higher anti-FHA and anti-PT levels than infants who received DTaP-12.5. No rise in the agglutinin titres was noted for recipients of the acellular vaccines although this vaccine stimulated increases in agglutinins when given as the fourth or fifth dose to children who had received three doses of DTP. The rates of erythema, induration, pain, irritability, crying, increased sleepiness, and decreased appetite were significantly (P</=0.05) lower in infants who received acellualr vaccines than in infants who received DTP. When the data from the injections at 2, 4 and 6 months of age were combined, no significant differences in the rates of any adverse event were noted for recipients of DTaP-12.5 or DTaP-25. The rates of most adverse reactions following DTP decreased from the first to the third immunization except fever, which increased. For acellular vaccine recipients, the rates of fever and erythema increased somewhat from the first to the third injection but remained far below the rates following DTP. The acellular vaccine was safe and immunogenic, and a dose-response effect was demonstrated.

Adhesins, Bacterial↗

PubMed1998

Endogenous yolk steroid hormones in turtles with different sex-determining mechanisms.

Maternal transfer of nutrients, including steroid hormones, to embryos during gestation in viviparous amniotes is well known, but the concordant process in oviparous amniotes is poorly understood. Recent evidence suggests that steroid hormones are present in freshly laid eggs of archosaurs and that their concentrations may influence offspring phenotypes. This process might be especially important in reptiles with temperature-dependent sex determination (TSD), because embryonic sex determination as well as other traits is thought to be influenced by temperature-dependent steroid metabolism. To evaluate the potential importance of endogenous steroid hormones to developing reptilian embryos, we (1) measured testosterone and estradiol-17beta levels in fresh eggs from natural populations of three species of turtles with TSD and two with genotypic sex determination (GSD), (2) evaluated testosterone concentrations within and among clutches of two turtle species with TSD, and (3) correlated clutch testosterone concentrations with incubation length, body mass, and sex ratio of offspring of two turtle species with TSD from eggs incubated at pivotal sex-determining temperatures. Turtles with TSD had higher levels of yolk testosterone (up to approximately 300 ng/g) than turtles with GSD (up to approximately 15 ng/g), suggesting a potential functional dichotomy between these two classes of sex-determining mechanisms; concentrations of yolk estradiol-17beta were low and fairly uniform among all five species (approximately 1 ng/g). Yolk testosterone varied substantially among, and relatively little within, clutches, indicating considerable potential as a mechanism behind clutch effects on offspring phenotypes. Steroid concentrations were unrelated to order of oviposition, unlike in birds, but yolk testosterone levels were correlated with incubation length and possibly with offspring sex ratio. Embryos of Chelydra serpentina serpentina from clutches with higher yolk testosterone hatched soonest at 21.8 degreesC; the opposite was true for Trachemys scripta elegans embryos incubated at 28.2 degreesC. At 27.6 degreesC, C. s. serpentina clutches with higher yolk testosterone produced more male-biased offspring sex ratios. Taken together, these results are strikingly consistent with published data on other oviparous amniotes and with the known physiology of follicular development and embryonic sexual differentiation in these disparate taxa. The findings of these experiments suggest that yolk testosterone in turtle eggs may be biologically significant.

Animals↗

PubMed1998

Evidence for the existence of a surface receptor for ferriclactoferrin and ferrictransferrin associated with the plasma membrane of the protozoan parasite Leishmania donovani.

Previous work has demonstrated the ability of the promastigote form of the protozoan parasite Leishmania chagasi to utilize iron chelated to lactoferrin and transferrin for growth and metabolism. We have obtained evidence suggesting that the promastigote form of the parasite possesses specific binding sites for lactoferrin and transferrin. Lactoferrin binding appears to be: 1) independent of whether or not the protein contains iron; 2) not inhibited by transferrin; and 3) independent of whether the organism is in log or stationary phase of growth. Transferrin binding is: 1) markedly greater if the protein is iron loaded; 2) inhibited by the presence of lactoferrin; and 3) independent of whether the organism is in log or stationary growth phase. Preliminary ligand blot analyses are consistent with the presence of a protein or proteins which bind lactoferrin and/or transferrin. The relationship to these binding sites to those described in other protozoan species requires further investigation.

Animals↗

PubMed1998

Characterization of lower temperature storage limitations of fresh-extended porcine semen.

Irreversible damage caused by cold shock has been assumed to occur when boar semen is exposed to temperatures below 15 degrees C. Identification of the lower critical temperature at which extended boar semen undergoes cold shock, however, has yet to be defined. The aims of this study were to 1) identify the cold-shock critical temperature and time on extended boar semen as assessed by sperm motility and morphology, and 2) determine the effects on fertility of using extended porcine semen exposed to this critical temperature and time. For Objective 1, ejaculates from 18 boars were collected, analyzed and extended in Androhep to 50 x 10(6) sperm/mL. Doses (4 x 10(9) sperm) from each ejaculate were exposed to 5 storage temperatures (8, 10, 12, 14 and 17 degrees C). Sperm motility and morphology (including acrosomes) were assessed following collection and at 12-h intervals for 48-h. Decreases in sperm motility occurred within the first 12-h at all temperatures. Sample motility dropped below 70% within 12-h in the 8 degrees C group and by 48-h in the 10 degrees C group. Sample motility was > 75% in the 12, 14 and 17 degrees C (control) groups throughout the trial. The percentage of morphologically abnormal sperm cells, including acrosomes, did not change within or between treatment groups over the 48-h storage period. In Objective 2, boar ejaculates (n = 9) were handled as in the first objective and were equally divided into treated (12 degrees C for < or = 60-h) and control (17 degrees C for < or = 60-h) groups. Using a timed, double insemination technique, 135 sows were bred by AI using either 12 degrees C (n = 74) or 17 degrees C (n = 61) extended, stored semen. No differences were observed in the farrowing rate (93 vs 95%), total offspring born (11.58 vs 11.61) or number live born (10.68 vs 10.63) between 12 and 17 degrees C groups, respectively. The results demonstrate that acceptable fertility can be obtained with Androhep extended boar semen exposed to temperatures as low as 12 degrees C for up to 60-h, and that cold shock appears to occur in vitro when extended boar semen is exposed to storage temperatures below 12 degrees C.

Acrosome↗

PubMed1998

Iron acquisition by parasitic protozoa.

The efficient uptake of iron by microorganisms is essential for their survival. Mammalian hosts possess elaborate means of sequestering their iron stores to protect themselves against invading pathogens. In this review, Mary Wilson and Bradley Britigan summarize mechanisms by which bacteria and protozoa effectively scavenge iron from their hosts during infection, as well as the potential and proven effects of these mechanisms on microbial virulence.

Journal Article↗

PubMed1998

Outcomes and ocular growth rates after intraocular lens implantation in the first 2 years of life.

PURPOSE: To evaluate the outcomes and ocular growth after intraocular lens (IOL) implantation in the first 2 years of life. SETTING: University-affiliated eye institute. METHODS: The medical records of consecutive children under 24 months of age who had cataract extraction with IOL implantation were reviewed. Change in axial length over time, postoperative complications, need for additional surgery, predicted versus actual postoperative refraction, and visual outcomes were recorded. Complication rates were compared with those in a similar group of age-matched patients who were left aphakic at the time of surgery. RESULTS: Twenty-two eyes of 17 patients aged 12 days to 22 months had IOL implantation. Length of follow-up ranged from 2 to 36 months (mean 14 months). Visual acuity measurement, limited to fixation-preference testing in most patients, revealed amblyopia in the operated eye in the majority of cases. Postoperative refractive error, predicted using the Holladay formula, showed a mean error in prediction of 1.5 diopters (D) (range -1.8 to 4.1 D). Serial axial lengths in 11 patients with a mean follow-up of 20 months showed no significant difference in growth in the fellow versus the operated eye. There was no significant difference in complication rates between pseudophakic patients and the age-matched aphakic group. However, in 14 of 32 aphakic eyes (44%), a notation in the chart indicated that the patient had stopped wearing glasses or contact lenses for at least 2 months. CONCLUSION: Intraocular lens implantation appeared to be a safe and effective alternative to contact lens or spectacle correction of aphakia in children younger than 2 years of age. It may aid amblyopia treatment by eliminating periods of uncorrected aphakia.

Aphakia, Postcataract↗

PubMed1998

Skin problems in the traveler.

Skin lesions are common in travelers and include a mix of mundane dermatologic problems and rare diseases acquired only in remote or tropical regions. The morphology, distribution, and progression of the lesions are useful in assessing possible causes. Early in the evaluation it is important to determine whether the patient might have a process that is rapidly progressive, treatable, or transmissible. In addition to routine laboratory studies, biopsy and serologic tests are often necessary to confirm a specific diagnosis.

Helminthiasis↗

PubMed1998

Direct actions of gonadal steroid hormones on FSH secretion and expression in the infantile female rat.

FSH-beta mRNA is dramatically regulated in the infantile female rat anterior pituitary. Elevated plasma levels of FSH correspond with increased FSH-beta mRNA levels which peak on PND 12. The source of this regulation does not appear to be GnRH, since the administration of a potent GnRH antagonist does not suppress FSH-beta mRNA levels. Consequently, we have examined the effects of the gonadal steroid hormones, estrogen and androgen, on the maintenance of gonadotropin secretion and gene expression both in vivo and in vitro. Androgen and estrogen action was blocked in vivo with the specific receptor antagonists, flutamide (150 microg) and tamoxifen (200 microg). Administration of antagonists during two different three day time-periods of infantile life [postnatal day (PND) 8-11 and PND 11-14] resulted in differing effects on both FSH and LH secretion as well as on FSH-beta and LH-beta mRNA levels. Flutamide and tamoxifen treatment both suppressed FSH secretion at either age examined (p < 0.01). LH secretion was suppressed by both treatments but only at the younger of the two ages (p < 0.01). In contrast to its effects on FSH secretion, tamoxifen suppressed FSH-beta mRNA levels in the later group only. LH-beta mRNA levels were suppressed by tamoxifen, but only in the younger age group (p < 0.05). The direct effects of steroid hormones on infantile pituitary gonadotrophs were examined in vitro by incubating cells with dihydrotestosterone propionate (DHTP; 10(-8) M) or 17beta-estradiol (E; 10(-8) M). Both DHT and E treatment stimulated FSH secretion when measured 48 h later (p < 0.01). There were no effects on LH secretion. FSH-beta mRNA levels were also stimulated by DHT at 48 h (p < 0.01). Estradiol treatment transiently increased FSH-beta mRNA levels at 2 and 6 h following treatment (p < 0.01) but not at 48 h. LH-beta levels were suppressed by DHT treatment (p < 0.05), and E transiently elevated LH-beta mRNA levels at 2 h (p < 0.05). Taken together these studies indicate that gonadotrophs from infantile female rats are capable of responding directly to steroid hormones, and may play a role in the selective stimulation of FSH secretion and expression in vivo.

Animals↗

PubMed1998

Acquired cataracts after argon laser photocoagulation for retinopathy of prematurity.

PURPOSE: Our purpose was to determine the incidence of cataract after argon laser photocoagulation of the retina in infants with retinopathy of prematurity (ROP). METHODS: We reviewed medical records of 189 consecutive infants undergoing argon laser photocoagulation for acute ROP between 1993 and 1996. Birth weight, estimated gestational age at birth, chronologic and postconceptional ages at the time of treatment, ROP outcome, and the postoperative occurrence of cataract were recorded. RESULTS: A total of 374 eyes in 189 infants were treated for threshold ROP. Mean birth weight was 916 gm (range 480 to 2500 gm), mean postconception age at birth was 26.4 weeks (range 23.5 to 34 weeks), and mean postconception age at surgery was 36.2 weeks (range 33 to 47 weeks). A favorable anatomic outcome occurred in 90% of eyes. However, severe macular traction, macular fold, or retinal detachment developed in 10% of eyes. A total of four eyes (1%) had cataracts. Laser-induced cataracts were diagnosed in only two eyes. A third eye had a posterior subcapsular cataract that may or may not have resulted from the laser treatment. In a fourth patient a unilateral punctate opacity judged to be visually insignificant was noted at surgery but it was not progressive. All patients who had cataracts had a persistent tunica vasculosa lentis; however, there was no statistically significant difference in the incidence of cataract formation in eyes with persistent tunica vasculosa lentis compared with eyes without it (p = 0.057). CONCLUSION: Argon laser photocoagulation remains an effective alternative to transscleral cryotherapy in the treatment of threshold ROP. The incidence of cataract formation is approximately 1% and may be more likely to occur when persistent hyaloidal vessels are present on the lens.

Birth Weight↗

PubMed1998

Haematological changes associated with influenza vaccination in people aged over 65: case report and prospective study.

Blood count abnormalities are a recognized feature of many viral infections and immunizations but little is known about the haematological effects of influenza vaccination. We report a 67-year-old patient who developed thrombocytopenia and severe neutropenia 3 weeks after she was vaccinated against influenza. The case led us to study prospectively the blood counts of 70 people aged over 65 before and after they received influenza vaccine. There were no significant changes in the levels of haemoglobin, neutrophils, monocytes, eosinophils or platelets after vaccination, but the total WBC counts (mean +/- SD, 6.86 +/- 1.52) and lymphocyte counts (1.69 +/- 0.61) were significantly lower at 4 weeks than at baseline (7.22 +/- 1.60 [P = 0.02] and 1.86 +/- 0.62 [P = 0.001] respectively) and in four subjects the lymphocyte count fell to below 0.7 x 10(9)/l. Since influenza vaccine does not contain live virus, its haematological effects presumably relate to the host immune response rather than to viral replication.

Aged↗

PubMed1998

Unresponsive CD4+ T lymphocytes from Leishmania chagasi-infected mice increase cytokine production and mediate parasite killing after blockade of B7-1/CTLA-4 molecular pathway.

Infection of BALB/c mice with Leishmania chagasi results in progressive increase of parasite burden in spleen, in spite of extensive T cell activation in situ. Explanted splenic CD4+ T cells showed decreased proliferation to anti-CD3, compared with controls, and no response to L. chagasi recombinant antigen Lcr1. Blockade of the negative costimulatory receptor CTLA-4 restored responses to anti-CD3 and induced vigorous responses to Lcr1. Blockade of B7-1, but not B7-2, also enhanced T cell responsiveness. CTLA-4 blockade completely restored activation-induced interleukin-2 secretion and increased interferon-gamma production. The effect, however, was not restricted to Th1 responses, since CTLA-4 blockade also enhanced antigen-induced interleukin-4 secretion. CTLA-4 blockade induced almost complete elimination of parasite burden in splenocyte cultures activated with anti-CD3 or Lcr1. These results indicate that CTLA-4 engagement by B7-1 plays an important role in maintaining unresponsiveness in CD4+ T cells in this model of chronic visceral leishmaniasis.

Abatacept↗

PubMed1998

Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats.

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.

Animals↗

PubMed1998

Development of Meishan and Yorkshire littermate conceptuses in either a Meishan or Yorkshire uterine environment to day 90 of gestation and to term.

To investigate the impacts of uterine type and conceptus genotype on development through late gestation, Meishan and Yorkshire embryos were co-transferred into the uteri of either Meishan or Yorkshire recipients that were subsequently slaughtered on Day 90 of gestation. At slaughter, regardless of conceptus genotype, fetuses and placentae were markedly smaller when recovered from Meishan than from Yorkshire recipients. Whereas Meishan and Yorkshire fetuses recovered from Meishan uteri were similar in weight, Meishan fetuses were markedly lighter than littermate Yorkshire fetuses when recovered from Yorkshire uteri. Because of the marked differences between fetal weights observed in Yorkshire recipients on Day 90 of gestation, Meishan and Yorkshire embryos were co-transferred to Yorkshire recipients that were allowed to farrow. Surprisingly, Meishan and Yorkshire fetuses cogestated in Yorkshire recipients were born at similar weights, whereas Meishan placentae were markedly smaller. The weight of Meishan placentae were similar on Day 90 and at term, whereas the weight of Yorkshire placentae were markedly larger (approximately 70%) at term than on Day 90. The constant weight of Meishan placentae from Day 90 to farrowing appears to result from an ability to increase their vascularity during this interval. In contrast, Yorkshire placentae may be forced to increase their weight to keep pace with fetal growth during this period. Because uterine capacity sets the upper limit on litter size, the decreased endometrial surface area required per conceptus in the Meishan pig seems to explain its greater potential for increased litter size.

Animals↗

PubMed1998

Activin subunit, follistatin, and activin receptor gene expression in the prepubertal female rat pituitary.

In the prepubertal female rat, a transient and selective increase in FSH secretion and mRNA expression by the pituitary gland occurs toward the end of the second postnatal week of life. To begin to investigate the possibility that activin may play a role in up-regulating FSH during this time, we have studied the ontogeny of the expression of the activin ss subunits, follistatin, and activin receptor subtypes in the prepubertal female rat pituitary. The levels of expression of ssA, ssB, and follistatin mRNAs were determined in the pituitary gland on postnatal days (PND) 8, 10, 12, 15, and 21 by semiquantitative reverse transcription-polymerase chain reaction. All values were compared to those of adult females killed on diestrus. mRNA levels of subunit ssA were significantly (p < 0.05) elevated on all postnatal days examined; ssB mRNA levels were elevated above adult levels only on PND 10 (p < 0.05). Follistatin mRNA was high on PND 8 (p < 0.05) and then decreased to adult levels. The level and distribution of activin receptor type II subtype mRNAs were determined by in situ hybridization. Activin receptor type II (Act RII) mRNA expression was diffusely expressed throughout all areas of the pituitary. Activin receptor type IIB (Act RIIB), on the other hand, was highly expressed by a subset of anterior pituitary cells. In situ hybridization for activin receptor subtype mRNAs was combined with immunocytochemistry to detect FSH-containing cells. We determined that in the infantile female pituitary, Act RII mRNA was generally not expressed in FSH-immunoreactive cells, while Act RIIB mRNA was expressed in FSH-immunoreactive cells. Act RII mRNA was lower on PND 10 and 15 when compared to PND 21 (p < 0.05), whereas Act RIIB mRNA expression did not change with age. These data suggest that the essential components of the activin regulatory system are present in the infantile female pituitary gland and thus may be involved in the differential regulation of FSH at this time.

Activin Receptors↗