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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1997

Administration of IGF-I affects the GH axis and adolescent growth in normal monkeys.

The present study examined the effects of IGF-I on serum concentrations of IGF binding protein-3 (IGFBP-3) and GH and assessed how treatment with estradiol and IGF-I would stimulate adolescent growth in monkeys with normal pituitary function. In study I, ovariectomized, juvenile female rhesus monkeys (21 months of age; n = 6) received a bolus injection of IGF-I (1 mg/kg s.c.) and serum samples were collected periodically through 48 h. The consequential elevation in serum IGF-I resulted in a parallel increase in serum IGFBP-3 at 1 and 3 h after treatment with values returning to baseline by 7 h. In contrast, the elevation in serum IGF-I resulted in a significant decline in serum GH within 3 h of treatment. These data confirm that an elevation in IGF-I increases IGFBP-3 while simultaneously acting in a negative feedback capacity to inhibit GH. In study II, ovariectomized, juvenile female rhesus monkeys served either as controls (Con, n = 6) or received a constant s.c. infusion of IGF-I (300 micrograms/day; Igf, n = 6) from 13 through 32 months of age. At approximately 26 months, females entered an estradiol-treatment protocol in which they received alternating blocks of 3 weeks of estradiol followed by 3 weeks of no estradiol. As found in study I, the elevation in serum IGF-I resulted in a significant increase in serum IGFBP-3 throughout the study in Igf compared with Con females. Estradiol administration significantly increased serum IGF-I and IGFBP-3 levels in both groups. Although the nano-molar ratio of IGF-I to IGFBP-3 was consistently higher in Igf females, the magnitude of the change in IGF-I:IGFBP-3 following estradiol treatment was similar between groups. Finally, the age-dependent increase in serum GH was dampened in Igf compared with Con females and the increase in response to estradiol was less in Igf females. Although total growth in crown-rump length was similar in both groups, Igf females grew more prior to estradiol replacement while Con females grew more once estradiol treatment was initiated. In addition, skeletal maturity was advanced more quickly in Igf females once estradiol treatment had been initiated. These data suggest that, in female monkeys with normal pituitary function, IGF-I administration inhibits endogenous GH secretion but is capable of stimulating crown-rump growth. Although IGF-I increased serum levels of IGFBP-3, the increase was not proportional to the increase in serum IGF-I achieved by the treatment. These data would suggest that IGF-I may regulate the release of this binding protein but that GH may be required to maintain equi-molar proportions of IGF-I to IGFBP-3. In addition, the observation that serum concentrations of IGF-I were increased further in IGF-I-treated females by the administration of estradiol without a change in serum GH, suggests that estradiol has a direct effect on IGF-I synthesis and release independent of GH.

Animals↗
PubMed1997

Lack of a nocturnal rise in serum concentrations of melatonin as gilts attain puberty.

Twenty prepubertal crossbred gilts (Yorkshire x Hampshire x Duroc) weighing 98.1 +/- 4.2 kg at 5 mo of age were placed in an environmentally controlled room having a temperature of 18 degrees C and light:dark cycle of 12 h:12 h. Light intensity measured 700 lx at eye level to the gilts. Three mature ewes were penned adjacent to the gilts to serve as positive controls for the light-dark cycles. After a 30-d acclimation period, 10 gilts from the pool determined to be prepubertal (serum progesterone < 500 pg/mL) were fitted with surgically implanted jugular catheters. Blood samples were drawn at 1100 (4 h after onset of light), 1130, 1200, 2300 (4 h after onset of darkness), 2330, and 2400 for 4 d. On d 5 of sampling, gilts were transported in an open-bed truck for 15 min, returned to their original environment, and exposed to boars for 20 min. Boar exposure was repeated every day throughout the remainder of the experimental period. Blood samples were drawn from each gilt until 7 d after estrus or for 12 d in those gilts that did not exhibit estrus. Blood samples were drawn by venipuncture from the ewes during the entire experimental period. For each sampling day, within an individual gilt or ewe, means of serum concentrations of melatonin (MEL) for night (scotophase) and day (photophase) samples were calculated. After three replications were conducted, four classes of animals were obtained: ewes (n = 9); nonpubertal gilts (n = 10); and two classes of gilts that ultimately reached puberty (prepubertal [n = 16] and postpubertal [n = 16]). Across all gilts, only 65 of 406 bleeding periods (16.0%) had a nocturnal (scotophase) rise in serum MEL. The proportion of gilts expressing a nocturnal rise in serum MEL did not differ as gilts approached puberty (P > .05). Incidence of nocturnal rises of MEL was similar (P > .05) in gilts that attained puberty and gilts that did not attain puberty. Nocturnal rises in MEL were observed in 86.2% of the bleeding periods of ewes housed in the same environment. These data indicate clearly that nocturnal rises in serum MEL are not necessary for a gilt to attain puberty.

Animals↗
PubMed1996

Evaluation of tuberculosis control policies using computer simulation.

OBJECTIVE: To develop more effective methods to assess tuberculosis (TB) control strategies so we can meet national goals for the elimination of TB in the United States. DESIGN: Using a semi-Markov model that divided the US population into 3 age groups and 18 clinical states based on disease status and risk for TB and human immunodeficiency virus (HIV) infection, we measured the effects of 5 changes in TB policy, introduced singly and in combination: (1) increased coverage and (2) improved efficacy of preventive therapy, (3) increased coverage and (4) improved efficacy of treatment, and (5) introduction of BCG vaccination. RESULTS: A BCG vaccination program that reached 10% of eligible children and 1% of eligible adults each year would produce a 17% reduction in cases and an 11% decline in deaths over 10 years. Preventive therapy programs among the general population would have little effect on the number of TB cases, but a program targeting HIV-infected patients would reduce HIV-associated TB cases and deaths 14% to 20%. A 10% improvement in the coverage and efficacy of both preventive therapy and treatment, coupled with the BCG vaccination program, would lead to a 47% decline in TB cases and a 50% decline in TB deaths relative to baseline over 10 years. CONCLUSIONS: Improvements in treatment coverage or effectiveness alone are unlikely to reach established national goals for the elimination of TB. These goals can be achieved through a combination of improvements in current programs with targeted preventive therapy and BCG vaccination programs.

Adolescent↗
PubMed1996

Structures of the antigenic O-polysaccharides of lipopolysaccharides produced by Actinobacillus actinomycetemcomitans serotypes a, c, d and e.

Actinobacillus actinomycetemcomitans is a gram-negative capnophilic coccobacillus that has been implicated in the etiology of certain forms of early-onset periodontitis as well as non-oral infections, mostly bacterial endocarditis. Five distinct serotypes of A. actinomycetemcomitans have been described. Although the O-polysaccharide (O-PS) of lipopolysaccharide (LPS) has been shown to define the serologic specificity for this species, only the structure of the O-PS of serotype b has been characterized. The focus of the current study was to define the structures of the O-PS of A. actinomycetemcomitans serotypes a, c, d and e. Structure determination was accomplished through the use of methylation, periodate oxidation, and one-dimensional and two-dimensional NMR methods. The O-PS of A. actinomycetemcomitans (OMZ-542) serotype d had [alpha]D +15 degrees and was composed of D-glucose, D-mannose and L-rhamnose (L-Rha) in a molar ratio of 1:2:1. Methylation, periodate oxidation, and two-dimensional 1H-NMR and 13C-NMR studies showed that the antigenic O-PS was a high-molecular-mass polymer composed of repeating tetrasaccharide units with the structure: [formula: see text] The O-PS of the LPS produced by A. actinomycetemcomitans (ATCC 29523) serotype a had [alpha]D +150 degrees and was found to contain 6-deoxy-D-talose (6dTalp) and O-acetyl (2:1) and was a high-molecular-mass polymer composed of O-acetyl-substituted repeating disaccharide units with the structure: [formula: see text] The O-PS of the LPS of A. actinomycetemcomitans (SUNY 67) serotype c had [alpha]D -170 degrees and was composed of 6-deoxy-L-talose and O-acetyl (2:1). Structural analysis showed that the O-PS was a high-molecular-mass polymer of repeating disaccharide units with the structure: [formula: see text] The O-PS of the LPS of A. actinomycetemcomitans (OMZ 534) serotype e had [alpha]D +57 degrees and was composed of 2-acetamido-2-deoxy-D-glucose and L-rhamnose (1:1) and by chemical and NMR analysis was found to be a polymer of repeating disaccharide units with the structure: -->4)-alpha-D-GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi.

BALB/c mice are susceptible to infection with the visceralizing species of Leishmania, Leishmania chagasi. The parasite load initially rises in the liver and spontaneously subsides, whereas parasite multiplication begins later and remains lower in the spleen. To investigate whether this organ-specific multiplication of L. chagasi correlates with localized immune responses, we compared cytokine production by splenic vs hepatic immune cells. Livers from infected mice contained granulomas harboring intracellular L. chagasi amastigotes, whereas few amastigotes were present in the spleen. FACS analysis granuloma cells showed granuloma lymphocytes expressed a memory/effector phenotype. Granuloma cells cultured in vitro produced IL-10 and IL-6 but no detectable IFN-gamma, IL-4 or IL-5. In contrast, splenocytes from the same animals secreted IFN-gamma, IL-4, IL-6, and IL-10. T cells were depleted from granuloma cells by immune lysis, and the results indicated that IL-10 and IL-6 were derived at least in part from a non-T cell compartment. Paradoxically, FACS-purified Thy-1+ granuloma lymphocytes were able to produce IFN-gamma in the absence of other granuloma cells, suggesting IFN-gamma production might usually be inhibited by a granuloma-associated non-T cell element. Coculture of splenocytes with either granuloma cells or supernatants from granuloma cultures inhibited the usual splenocyte production of IFN-gamma and IL-4 but not IL-10. Thus, there may be a unique granuloma-associated suppressive factor accounting for the absence of IFN-gamma in hepatic granuloma cultures. It may be the absence of IFN-gamma in the liver and presence in the spleen that allows or inhibits parasite survival, respectively, in these different locations.

Animals↗
PubMed1996

Leishmania chagasi: a gene encoding a protein kinase with a catalytic domain structurally related to MAP kinase kinase.

The gene for a serine/threonine protein kinase was isolated from Leishmania chagasi. The deduced amino acid sequence encoded by this Leishmania protein kinase (LPK-1) gene possesses all of the 11 conserved subdomains found in most other serine/threonine protein kinase catalytic domains. Sequence alignment with other known protein kinases demonstrates that the 42-kDa LPK-1 is a member of the mitogen-activated protein kinase kinase family involved in the signal-transduction pathways in yeast and mammalian cells. The single copy gene for LPK-1 specifies a 3.1-kb mRNA that is expressed in both logarithmic and stationary phase promastigotes with a twofold higher steady-state level in the infective stationary phase promastigotes.

Amino Acid Sequence↗
PubMed1996

Absence of detrimental effects of fluoride exposure in diabetic rats.

This study is part of a comprehensive programme to investigate fluoride toxicity and the hypothesis that fluoride ingested by "medically compromised' animals will result in altered physiological function. Its objectives were to monitor fluoride retention, tissue fluoride concentrations and genetic variables in diabetic and control rats chronically exposed to fluoride, and to determine whether or not adverse effects occurred. Male, Zucker fatty diabetic rats and Zucker age-matched lean controls were fed a low-fluoride diet ( < 1.2 parts/10(6) F-) ad libitum and received 0, 5, 15 or 50 parts/10(6) fluoride in their drinking water for 3 or 6 months. Fluoride metabolic balance was determined for 4 days before the end of each study phase. Plasma and urine were analysed for biochemical markers of tissue function, and plasma, urine, faeces and tissues were analysed for fluoride. Bone marrow cells from animals killed after 6 months of treatment were examined for frequency of sister chromatid exchange, a marker of genetic damage. The diabetic rats consumed, excreted and retained significantly greater amounts of fluoride than the controls (p < 0.05). There were dose-related increases in fluoride excretion, retention and tissue concentrations in both classes of animals, which were significantly greater in the diabetic rats. In spite of greater amounts of fluoride in the tissues of diabetic animals, there was no evidence, under these experimental conditions, that any of the fluoride exposures tested caused measurable adverse effects on the physiological, biochemical or genetic variables that were monitored.

Analysis of Variance↗
PubMed1996

5' sequences essential for trans-splicing of msp (gp63) RNAs in Leishmania chagasi.

The 5' sequences essential for spliced leader (SL) addition to RNA encoding the abundant Leishmania surface protease gp63 were determined. A DNA segment found upstream of all Leishmania chagasi gp63 genes was cloned in front of a luciferase gene, and luciferase activity was measured in transiently transfected L. chagasi promastigotes. Two hundred and twenty bp of the upstream region was needed for optimal luciferase activity. Deletions and point mutations were placed in this segment to determine which nucleotides participate in the splicing events. A region containing 87% pyrimidines located between 31 and 69 bp upstream of the splice acceptor dinucleotide and containing three potential branch point A residues was highly beneficial for reported gene activity. In contrast, a 30-nt pyrimidine-rich sequence immediately upstream of the splice acceptor site did not by itself enhance luciferase activity. Luciferase activity was associated with the presence of trans-spliced luciferase mRNA. The results suggest that sequences 31-69 bp upstream of gp63 genes enhance gene expression through provision of signals for efficient trans-splicing.

Animals↗
PubMed1996

The promoter for the ribosomal RNA genes of Leishmania chagasi.

A promoter for the rRNA genes of Leishmania chagasi was found to be located about 1 kb upstream of the 18S rRNA coding region and immediately downstream of 64 bp tandem repeats. Its approximate boundaries and corresponding transcription start site were determined by transient transfections and primer extension assays. This promoter for RNA polymerase I has differing activities when transfected into various Leishmania species and no activity in Trypanosoma cruzi. Its sequence has no obvious similarities with other known rRNA promoters in Trypanosomatids. Depending on the species, this promoter can be used to increase expression of a protein from a plasmid in Leishmania by as much as 45-fold over that from a plasmid lacking a promoter.

Animals↗
PubMed1996

Visceral leishmaniasis.

Visceral leishmaniasis presents a serious problem in endemic regions that is difficult to treat or prevent. Several epidemiologic problems make the disease particularly troublesome to manage. These include the facts that classic visceral leishmaniasis is fatal if untreated and there is not reliable access to medical care in many endemic regions. When available, treatment has associated toxicity and requires the use of intravenous medications with careful monitoring for toxicity, which are complex to administer in underdeveloped nations. There is an increasing incidence of the disease in HIV-infected individuals in southern Europe, in part because of the fact that eradication of the organism from infected persons using currently available drugs appears to be difficult if not impossible. Furthermore, chronic cutaneous forms of the disease allow humans and animals to maintain the organism long-term in a bodily site that is easily accessible to the sandfly vector. More effective and less toxic treatment modalities as well as a protective vaccine are badly needed to manage this disease.

Animals↗
PubMed1996

High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency.

Renal insufficiency is known to increase plasma fluoride levels, which may increase the risk of fluorosis and osteomalacia. The purpose of this study was to determine the effects of fluoride on skeletal fragility and mineralization in renal-deficient animals. We evaluated the skeleton of rats with surgically induced renal deficiency (4/5 nephrectomy) that were chronically exposed to fluoridated water at concentrations of 0, 5, 15, and 50 ppm for a period of 6 months. The chosen fluoride doses caused plasma fluoride levels equivalent to those in humans consuming fluoridated water levels of 0, 1, 3, and 10 ppm, respectively. Animals with renal deficiency drank about 60% more water and excreted 85% more urine than control animals. Glomerular filtration rate (GFR) was decreased 68% and plasma BUN was increased fourfold in rats with renal deficiency. Plasma fluoride was strongly correlated with 1/GFR and was greatly increased by renal deficiency in all animals consuming fluoridated water. There was a strong positive, nonlinear relationship between plasma fluoride and bone fluoride levels, suggesting nonlinear binding characteristics of fluoride to bone. The amount of unmineralized osteoid in the vertebral bone was related to the plasma fluoride levels. Vertebral osteoid volume was increased over 20-fold in animals with renal deficiency that received 15 or 50 ppm fluoride, suggesting osteomalacia. Should osteomalacia be defined as a tenfold increase in osteoid volume, there appeared to be a threshold plasma fluoride level of about 20 micromol/L, above which osteomalacia was observed consistently. This plasma fluoride level was not achieved in control rats regardless of fluoride intake, nor was it achieved in renal-deficient rats receiving 0 or 5 ppm fluoride. A fluoride concentration of 50 ppm reduced femoral bone strength by 11% in control rats and by 31% in renal-deficient rats. Vertebral strength also was decreased significantly in renal-deficient rats given 50 ppm fluoride. In conclusion, fluoridated water in concentrations equivalent to 3 and 10 ppm in humans, caused osteomalacia and reduced bone strength in rats with surgically-induced renal deficiency.

Alkaline Phosphatase↗
PubMed1996

Maternal recognition of pregnancy in swine. II. Plasma concentrations of progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha during the estrous cycle and during short and long pseudopregnancy in gilts.

Two experiments were conducted to determine plasma progesterone (P4) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations in unmated gilts induced to have either short pseudopregnancy (SPP) or long pseudopregnancy (LPP). In experiment 1, estradiol-17 beta (E2) was injected on different combinations of days between Days 11 and 16 of the estrous cycle. For gilts induced to exhibit SPP, the interestrous interval averaged 27.0 +/- 0.4 days compared to the control interval of 20.0 +/- 0.4 days. In experiment 2, E2 injections were given on Days 12 and 13 or on Days 12 through 25. Interestrous intervals in SPP and nonpseudopregnant gilts were 25.6 +/- 0.2 and 19.9 +/- 0.6 days, respectively. Four of six gilts treated with E2 on Days 12-25 were induced to have LPP lasting more than 100 days. In both experiments, plasma P4 declined to baseline approximately 3 days before posttreatment estrus, regardless of type of pseudopregnancy induced. Plasma PGFM peaked 4-6 days before posttreatment estrus in gilts displaying each type of response. In gilts exhibiting LPP, plasma PGFM concentrations tended to increase steadily during pseudopregnancy. These data suggest that the mechanisms of luteolysis during the estrous cycle of unmated gilts and during estrogen-induced SPP and LPP may be similar. The present results suggest that luteal persistence during SPP and LPP may be due to delayed peak release of prostaglandin F2 alpha by the uterus.

Animals↗
PubMed1996

Characterization of the O-polysaccharide structure of lipopolysaccharide from Actinobacillus actinomycetemcomitans serotype b.

We previously reported that the serotype b antigen of Actinobacillus actinomycetemcomitans is a constituent of the polysaccharide region of lipopolysaccharide (LPS) and contains significant amount of the neutral sugars rhamnose and fucose (M. Wilson and R. Schifferle, Infect. Immun. 59:1544-1551, 1991). In the present study, we determined the structure of the O antigen of A. actinomycetemcomitans Y4 (serotype b) LPS. Aqueous phase LPS was obtained from a phenol-water extract of A. actinomycetemcomitans Y4. This material was found to react with rabbit polyclonal antiserum to serotype b but not with antisera specific for other A. actinomycetemcomitans serotypes. Analyses revealed that the O polysaccharide of Y4 LPS consists of a polymer of trisaccharide repeating units composed of D-Fuc, AL-Rha, and D-GalNAc residues. An identical structure was obtained for the O polysaccharide of LPS from A. actinomycetemcomitans JP2, another serotype b strain. These results indicate that the serotype b antigen of A. actinomycetemcomitans is defined by a trisaccharide repeating unit present in the O polysaccharide of LPS.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Developmental changes in the expression of Leishmania chagasi gp63 and heat shock protein in a human macrophage cell line.

The ability of the protozoan Leishmania chagasi to infect a vertebrate host depends on its ability to survive intracellularly in a mammalian macrophage. Novel patterns of gene expression are probably important for conversion from the extracellular promastigote to the obligate intracellular amastigote parasite form. We found that the human macrophage-like cell line U937 provided an in vitro model of phagocytosis of L. chagasi promastigotes and intracellular conversion to amastigotes, allowing examination of parasite protein and RNA expression. The Leishmania surface protease gp63 assumed three isoforms during stage conversion, and a 64-kDa form of gp63 not present in promastigotes became the most prominent form in amastigotes. gp63 RNAs derived from the three different classes of msp genes (mspS, mspL, and mspC) were also differentially expressed. Infectious promastigotes contained mRNAs from mspS and mspC genes, whereas converting parasites expressed only mspL and mspC mRNAs. Sequence analysis of clones from an amastigote cDNA library confirmed the presence of gp63 mRNAs only from mspL and mspC class genes in tissue-derived amastigotes. Finally, 24 h after phagocytosis, there was a transient increase in the level of hsp70 and hsp90 proteins that subsequently decreased to baseline; this increase was not due to heat shock alone. We conclude that a unique pattern of selected L. chagasi proteins and RNAs is induced following phagocytosis by macrophages.

Animals↗