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Biomedical subjects

R D Peterson

Publications and source records attributed to R D Peterson.

At least 19 recordsLinked to original sources

Population genetics and gene variation of stable fly populations (Diptera:Muscidae) in Nebraska.

Genetic variation in stable fly, Stomoxys calcitrans (L.), populations from Nebraska, Canada, and Texas was sampled. Four of 12 allozyme loci were polymorphic, with an average of 1.7 alleles per locus. Observed and expected heterozygosities were 0.086 and 0.070, respectively. Nei's genetic distance between populations averaged 0.001 and ranged from 0.000 to 0.005. Wright's F statistics revealed greater variation within than among populations. Allele frequencies were homogeneous among temporal samples from a single population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of 6.4 kb of the mitochondrial DNA genome with 16 restriction enzymes revealed no variation in stable fly populations from Canada, Nebraska, and Texas. PCR-RFLP analysis of a 2.0-kb fragment of the nuclear ribosomal DNA internally transcribed spacer region also revealed no variation. The lack of genetic differentiation among stable fly populations indicates high levels of gene flow among populations. The low levels of variation observed with biochemical and molecular techniques are consistent with a genetic bottleneck during stable fly colonization of North America.

Animals

Mitochondrial DNA variation in screwworm.

Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to characterize mitochondrial DNA (mtDNA) variation in screwworms, Cochliomyia hominivorax, and secondary screwworm, C.macellaria, from the Caribbean, North America and South America. Four amplicons, totaling 7.1 kb, were analysed with sixteen restriction enzymes. A total of 133 restriction sites was observed in the two species, 104 in C.hominivorax, of which nineteen were variable, and ninety-five in C.macellaria, none of which was variable. Fourteen mtDNA haplotypes were observed among eighteen C.hominivorax examined. Mean divergence between C.hominivorax haplotypes (d) was 0.0064 substitutions per base-pair and genotypic diversity (G) was 0.97. Mean divergence between C.hominivorax and C.macellaria was 0.0824. Cochliomyia hominivorax haplotypes could be divided into three assemblages representing North America, South America and Jamaica, based on UPGMA clustering with d values. The assemblages did not exhibit complete geographic fidelity. These data were discordant with previously published allozyme data indicating little differentiation between screwworm populations. A scenario invoking historically isolated populations coming into contact with the introduction and movement of European livestock is proposed to explain the observed population structure of screwworm.

Animals

Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial.

OBJECTIVE: To test whether slow-release sodium fluoride inhibits spinal fractures and is safe to use. DESIGN: Placebo-controlled randomized trial. INTERVENTIONS: Slow-release sodium fluoride, 25 mg twice daily, in four 14-month cycles (12 months receiving sodium fluoride followed by 2 months not receiving it) compared with placebo. Calcium citrate, 400 mg calcium twice daily, continuously in both groups. PATIENTS: 48 of 54 patients who received sodium fluoride and 51 of 56 patients who received placebo completed at least 1 year of the study. All patients had postmenopausal osteoporosis. RESULTS: Compared with the placebo group, the fluoride group had a lower individual vertebral fracture rate (0.064 +/- 0.182 per patient-year compared with 0.205 +/- 0.297 per patient-year; P = 0.002), a higher unadjusted fracture-free rate (85.4% compared with 56.9%; P = 0.001), and a greater survival estimate (relative risk, 0.3 [95% CI, 0.12 to 0.76]) for new fractures. The recurrent spinal fracture rate did not differ between the two groups. The fluoride group had a substantial increase in L2-L4 bone mass of 4% to 5% per year for 4 years, a mean increase in femoral neck bone density of 2.38% +/- 3.33% per year, and no change in radial shaft bone density. The frequency with which minor side effects and appendicular fractures occurred was similar in the two groups; no patients developed microfractures or gastric ulcers. CONCLUSION: Slow-release sodium fluoride and calcium citrate administered for 4 years inhibits new vertebral fractures (but not recurrent fractures), augments spinal and femoral neck bone mass, and is safe to use.

Aged

Regulation of expression of aminopeptidase N in fetal rat lung by dexamethasone and epidermal growth factor.

Aminopeptidase N (EC 3.4.11.2) (APN) is an ectopeptidase expressed in lung at the apical surface of alveolar type II epithelial cells. Its expression is up-regulated during fetal lung development. Recently several ectopeptidases have been recognized as possible regulators of growth and cell differentiation through their role in hydrolysis of autocrine and paracrine peptides that influence these processes. The studies reported here describe effects of factors known to promote lung development and differentiation of the alveolar epithelium on expression of aminopeptidase N during fetal lung development in organ culture. Fetal rat lung was placed in organ culture at the 15th gestational day and cultured for 6 days in the presence or absence of the synthetic glucocorticoid hormone dexamethasone or epidermal growth factor (EGF). Steady-state levels of APN mRNA increased approximately 10-fold during the 6-day culture. During this time the lung alveolar epithelium developed to the point where immature alveolar type II cells were recognized by the presence of lamellar bodies. Dexamethasone or EGF increased the levels of APN mRNA in the fetal lung 2-to 3-fold over control cultures by the third day in culture and concurrently accelerated the morphological development of the alveolar epithelium. Differences in treated and control cultures diminished after 6 days in culture when the epithelium appeared more mature, suggesting that the immature epithelium was more responsive to the treatments.

Animals

1H NMR studies of the high-affinity Rev binding site of the Rev responsive element of HIV-1 mRNA: base pairing in the core binding element.

1H NMR studies of a 30-nucleotide RNA oligonucleotide (RBE3), which contains a high-affinity binding site for Rev of the HIV-1 Rev responsive element (RRE), two derivatives of RBE3 (RBE3AA and RBE3-A), and the complex of RBE3 with peptides derived from the RNA binding domain of HIV-1 Rev, are presented. The high-affinity binding site of the RRE consists of an asymmetric internal loop and surrounding Watson-Crick base pairs. In the wild-type RRE, one of the stems is closed by a loop; this is replaced in REB3 by the stable UUCG tetraloop. NOE data suggest that the internal loop of the free RNA contains structural features that have been predicted on the basis of in vitro selection experiments [Bartel, D.P., et al. (1991) Cell 67, 529-536]. The structural features include a Gsyn.Ganti base pair, a Ganti.Aanti base pair, and a looped out U. When the Rev peptide is bound to the RNA, the base pairs in the internal loop appear to be stabilized, although the RNA chemical shifts indicate that the RNA conformation undergoes some changes when bound by Rev peptide.

Base Composition

Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.

OBJECTIVE: To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications. DESIGN: A placebo-controlled, randomized trial. SETTING: Outpatient setting of specialty clinics in Dallas and Temple, Texas. INTERVENTIONS: Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously. PATIENTS: 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. MEASUREMENTS: Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry. RESULTS: In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia. CONCLUSIONS: Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

Aged

Correlation of nucleotide base and sugar protons in a 15N-labeled HIV-1 RNA oligonucleotide by 1H-15N HSQC experiments.

The advent of methods for preparing 15N- and 13C-labeled RNA oligonucleotides holds promise for extending the size of RNA molecules that can be studied by NMR spectroscopy. A practical limitation is the expense of the 13C label. It may therefore sometimes be desirable to prepare a relatively inexpensive 15N-labeled sample only. Here we show that the two-bond 1H-15N HSQC experiment can be used on 15N-labeled RNA to correlate the intranucleotide H1' and H8,H6,H5 resonances indirectly through the shared glycosidic nitrogen. The nonrefocused version of a standard HSQC experiment for 2D proton-detected 1H-15N chemical-shift correlation is applied in order to minimize the sensitivity loss due to the relatively fast spin-spin relaxation of RN oligonucleotides. The experiment is applied to the 30-nucleotide RNA RBE3 which contains the high-affinity binding site of the RRE (rev response element) for the Rev protein of HIV. The results indicate that this simple experiment allows a straightforward identification of the base proton resonances CH5, CH6, UH5, UH6, purine H8, and AH2 as well as the intranucleotide H1' and H8,H6,H5 connectivities. When combined with a NOESY experiment, complete sequential assignments can be obtained.

Base Sequence

Seasonal variation of vitamin A (retinol) status in older men and women.

OBJECTIVE: The present study was undertaken to determine vitamin A status in 59 free-living (26 males, 33 females) healthy older persons (65-74 years) in winter and summer. DESIGN: Three-day dietary intake data for vitamin A along with carbohydrate, lipid and protein were collected during the summer (June-September) and again during the winter (November-March). In addition, retinol and its carrier proteins, retinol-binding protein (RBP) and transthyretin (TTR), were measured in the plasma in each season. RESULTS: The mean vitamin A intake met the Canadian Recommended Intake (RNI) for both gender and season. However, probability analysis of dietary data revealed that 7 and 11% of males, and 8 and 14% of females, in summer and winter, respectively, were at risk of deficiency. None of the subjects in the present study exhibited biochemical evidence of vitamin A deficiency as determined by plasma levels of retinol and its transport proteins. Overall, the mean intake of vitamin A was significantly higher in males than in females; no seasonal effect was observed. On the other hand, the plasma levels of retinol and its carrier proteins were significantly lower in winter season than in summer, without any gender variation effect. CONCLUSION: Although mean values for dietary intake and plasma concentration of vitamin A may indicate nutritional adequacy, a small proportion of an older population may be at nutritional risk. The prevalence of risk appears to be generally higher in the winter than in the summer season and in females than in males.

Aged

Capsular compliance: a measure of a "hard" prosthesis.

Capsular contracture prevents a natural "feel" to an augmented breast and is frequently a source of patient and physician dissatisfaction postoperatively. The degree of hardness of a breast is difficult to quantitate. We have developed a rodent model that measures the pressure rise in a capsule in response to increasing intraluminal volume, generating a pressure-volume curve. The curve's break point determines the volume contained within the capsule and the slope of the steep part of the curve to the right of the break point determines capsule resistance to stretch and deformation. In a group of 14 rats, resistance to distension increased progressively over a 14-week period whereas capsule surface area, break point volume, and resting intraluminal pressure remained relatively constant. This model allows the assessment of changes in capsule contracture over time without having to kill the animal.

Animals

Function of integrin in duodenal mucosal uptake of iron.

A mechanism for the absorption of inorganic iron in the small intestine is described in which integrins appear to play an important role in the passage of iron across microvillous membranes. Biochemical isolates from microvillous preparations of duodenum from rats dosed with radioiron showed radioactivity concentrated in integrins. The presence of integrins on mucosal surfaces of duodenal cells was confirmed by immunofluorescent microscopy using anti-integrin monoclonal antibodies. Immunoprecipitation methods were used to show that microvillous radioiron was precipitated with anti-integrin antibodies and that mobilferrin, a 56-Kd cytosol iron-binding protein, coprecipitated with integrins. We postulate from these data that the mucosal uptake of iron from the gut lumen is mediated via an integrin-mobilferrin pathway.

Animals

Two- and three-dimensional HCN experiments for correlating base and sugar resonances in 15N,13C-labeled RNA oligonucleotides.

New 2D and 3D 1H-13C-15N triple resonance experiments are presented which allow unambiguous assignments of intranucleotide H1'-H8(H6) connectivities in 13C- and 15N-labeled RNA oligonucleotides. Two slightly different experiments employing double INEPT forward and back coherence transfers are optimized to obtain the H1'-C1'-N9/N1 and H8/H6-C8/C6-N9/N1 connectivities, respectively. The correlation of H1' protons to glycosidic nitrogens N9/N1 is obtained in a nonselective fashion. To correlate H8/H6 with their respective glycosidic nitrogens, selective 13C-refocusing and 15N-inversion pulses are applied to optimize the magnetization transfers along the desired pathway. The approach employs the heteronuclear one-bond spin-spin interactions and allows the 2D 1H-15N and 3D 1H-13C-15N chemical shift correlation of nuclei along and adjacent to the glycosidic bond. Since the intranucleotide correlations obtained are based exclusively on through-bond scalar interactions, these experiments resolve the ambiguity of intra- and internucleotide H1'-H8(H6) assignments obtained from the 2D NOESY spectra. These experiments are applied to a 30-base RNA oligonucleotide which contains the binding site for Rev protein from HIV.

Base Sequence

Human immune response to polydimethylsiloxane (silicone): screening studies in a breast implant population.

Although initially it was thought that polydimethylsiloxane (silicone) was biologically inert, recent published studies have demonstrated varying levels of IgG antibody reactive with this structure in humans. The objective of our study was to determine whether silicone implanted in humans results in a measurable immune response directed against a 3700 mol wt hydroxyl terminated silicone molecule and whether that response could be correlated with the level of presumed silicone exposure as inferred by clinical history. In a blind study, sera from 111 patients, with and without breast implants, were sent to a laboratory using an enzyme-linked immunosorbent assay to determine specific anti-silicone IgG antibody levels. Test results showed that patients with implants demonstrated statistically significant elevation in anti-silicone antibodies compared with the unimplanted control groups. The highest anti-silicone antibody levels were measured in implanted women with either frank implant ruptures or leakage of their silicone gel implants.

Adult

Association between maternal-fetal HLA-DR relationships and fetal growth.

PROBLEM: To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight. METHOD: A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal). RESULTS: After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate. CONCLUSION: Our findings supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.

Birth Weight

Expression of aminopeptidase N in fetal rat lung during development.

The ectopeptidase, aminopeptidase N, serves as a cell surface marker of the apical surface of the alveolar type II epithelial cell in adult lung. It is also present in fetal lung before differentiation of morphologically mature type II alveolar epithelial cells, suggesting that it is expressed by precursors of the type II cells. We have examined the mRNA coding for the aminopeptidase in adult and fetal lung and in mature type II cells and determined levels of mRNA and immunoreactive protein during fetal lung development. Comparison of the temporal patterns of steady-state levels of aminopeptidase mRNA and immunoreactive protein during development show that the expression of the protein is developmentally regulated and that expression is regulated, at least in part, at a pretranslational level. Both mRNA and immunoreactive protein levels increase severalfold on the final gestational day, suggesting that the function of the aminopeptidase may be associated with air breathing.

Aging

Maternal-fetal HLA-DR relationships and pregnancy-induced hypertension.

OBJECTIVE: Some studies have found an increased prevalence of pregnancy-induced hypertension among women sharing HLA antigens with their spouses or fetuses, thus supporting the hypothesis that maternal sensitization to fetal HLA alloantigens reduces the risk for pregnancy-induced hypertension. However, not all studies have confirmed these findings. No investigators have examined the four different types of maternal-fetal HLA relationships in their studies of pregnancy-induced hypertension. Our goal was to examine such associations to test further the HLA-allosensitization hypothesis. METHODS: We conducted a cohort study of pregnancy-induced hypertension among 683 nulliparous women. Women and their neonates were typed for HLA-A, -B, -DR, and -DQ antigens using serologic techniques to establish maternal-fetal relationships. RESULTS: We found an increased prevalence of pregnancy-induced hypertension when the fetus, but not the mother, was potentially exposed to HLA-DR alloantigens (maternal allogenicity) compared with the other three conditions combined (P < .003). Controlling for confounding factors, the increased prevalence of pregnancy-induced hypertension persisted in situations of maternal HLA-DR allogenicity (P < .007). CONCLUSIONS: Based upon our observations and other immunologic studies of pregnancy-induced hypertensive and uncomplicated pregnancies, we conclude that a maternal humoral response against fetal anti-HLA-DR immunoglobulin (IgG) antibody may influence the development of pregnancy-induced hypertension. This could occur when an immunocompetent fetus is exposed to maternal HLA-DR alloantigens, maternal exposure to fetal HLA-DR alloantigens alloantigens, maternal exposure to fetal HLA-DR alloantigens is not possible, and fetal IgG antibody bears paternally inherited markers allogeneic to the mother.

Eclampsia

In vitro lymphocyte activity in women with endometriosis--an altered immune response?

OBJECTIVE: To determine the possible role of the immune system in the pathogenesis of endometriosis. DESIGN: The lymphocyte proliferative response in the presence of autologous endometrial cells was assayed by tritiated thymidine incorporation. SETTING: Patients were recruited from a university outpatient clinic. MAIN OUTCOME MEASURE: To determine the lymphocyte proliferative response to endometrium in controls and patients with endometriosis. PARTICIPANTS: Twenty patients with endometriosis and 26 control women were studied. RESULTS: The lymphocyte proliferative response in the presence of autologous endometrium was significantly lower in women with endometriosis when compared with controls. CONCLUSION: This study indicates that an altered lymphocyte/endometrial cell relationship is operational in women with endometriosis and may contribute to the pathogenesis of the disease.

Adult