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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 163 records · Page 9Linked to original sources

Influence of anti-Actinobacillus actinomycetemcomitans Y4 (serotype b) lipopolysaccharide on severity of generalized early-onset periodontitis.

The objective of this study was to determine if a relationship exists between antibody reactive with the Actinobacillus actinomycetemcomitans serotype b lipopolysaccharide (LPS) and severity of periodontal disease in generalized early-onset periodontitis (G-EOP). The concentration of antibody reactive with A. actinomycetemcomitans serotype b LPS was determined for 102 G-EOP subjects. Analysis of the relationship between antibody reactive with A. actinomycetemcomitans serotype b LPS and measures of periodontal attachment loss indicated that the patients with the highest concentrations of antibody reactive with A. actinomycetemcomitans serotype b LPS had significantly less attachment loss. These high-responder subjects also had anti-A. actinomycetemcomitans serotype b LPS with significantly higher relative avidity. The results suggest that antibody reactive with A. actinomycetemcomitans serotype b LPS is protective in G-EOP patients.

Adult↗

Social status, mother-infant time together, and breastfeeding duration.

Chart review and direct observation were used to study the relationship between social status, mother-infant time together, and breastfeeding duration among 138 mothers who were breastfeeding at hospital discharge. Overall breastfeeding rate was 73 percent for patients with private insurance and 37 percent for patients without private insurance. Breastfeeding duration to six months was not related to social status. Mother-infant time together from birth through 48 hours was 3 hours greater for private insurance mothers. These three hours, which were statistically significantly different, did not correlate with breastfeeding duration in any way. Ancillary findings were that married mothers were more likely that unmarried mothers to be breastfeeding at six months, and that mothers who received epidurals were less likely to be breastfeeding at six months than mothers who did not receive epidurals.

Analgesia, Epidural↗

Short report: regulation of inducible heat shock protein 70 genes in Leishmania chagasi.

Eukaryotic and prokaryotic cells undergo an increase in heat shock proteins, including hsp70, during exposure to environmental stress and during some developmental changes. In trypanosomatid protozoa such as Leishmania sp. that cycle between poikilothermic vectors and mammalian hosts, this heat shock response occurs at programmed times in the parasite's life cycle. The increase in heat shock proteins in mammalian cells is initiated by an increased rate of transcription, resulting in greater amounts of total hsp70 RNA and protein. In contrast, we found a dramatic increase in hsp70 RNA during growth of Leishmania chagasi promastigotes from logarithmic to stationary phase in liquid culture, which was not accompanied by an increased amount of hsp70 protein. Furthermore, there was a 1.8-fold increase in hsp70 protein induced by exposure of L. chagasi to superoxide, but this was not associated with an increase in hsp70 RNA. We conclude that in contrast to higher eukaryotes, the amount of hsp70 protein produced by Leishmania sp. is not regulated by the steady state level of total hsp70 RNA.

Animals↗

A randomized controlled trial of prenatal pediatric visits for urban, low-income families.

BACKGROUND: Prenatal pediatric visits have been recommended by the American Academy of Pediatrics to allow the pediatrician to counsel parents on infant care issues, establish a supportive relationship, and provide pediatric practice information to parents. We hypothesized that prenatal pediatric visits would have an impact on breastfeeding decisions, health care behaviors, health care utilization, and the doctor-patient relationship. METHODS: We conducted a randomized controlled trial of prenatal pediatric visits for urban, low-income families to measure the impact on breastfeeding decisions, infant car safety seat use, circumcision, health maintenance, and emergency room visits and the pediatrician's perception that he/she would know the mother better. Pregnant women were recruited prenatally from the obstetrics clinic. Outcomes were measured by maternal interview prenatally and when the infant was 2 months old, in addition to review of the nursery record. Physicians were interviewed after the 2-month visit. Health care utilization was measured by chart review at 7 months. RESULTS: A total of 156 pregnant women were enrolled and randomized, 81 to the intervention group and 75 to the control group. Of mothers who breastfed, 45% in the intervention group changed their mind in favor of breastfeeding after enrollment compared with 14% in the control group. Mothers in the intervention group compared with the control group were more likely to make fewer emergency room visits, 0.58 compared with 1.0. Pediatricians were more likely to think that they knew mothers in the intervention group well, 54% versus 29% in the control group, yet 67% of mothers in both groups agreed their pediatrician knew them well. There were no differences between groups in initiation or duration of breastfeeding at 30 or 60 days, infant car safety seat use, circumcision, or health maintenance visits. CONCLUSIONS: Prenatal pediatric visits have potential impact on a variety of health care outcomes. Among urban, low-income mothers, we found beneficial effects on breastfeeding decisions, a decrease in emergency department visits, and an initial impact on the doctor-patient relationship. We suggest urban practices actively promote prenatal pediatric visits.

Adult↗

A silencer and an adjacent positive element interact to modulate the activity of the human insulin promoter.

A negative regulatory element (NRE) is located between positions -279 and -261 relative to the transcription start site of the human insulin gene. The NRE contains at least three distinct overlapping binding sites for several nuclear proteins. These proteins may be distinguished by their interaction with mutant variants of the NRE. Mutagenesis of two of these protein-binding sites within an insulin gene fragment containing sequences from position -361 to position +112 attenuated the negative activity of the NRE, confirming the importance of these sites in the function of the NRE. When placed in isolation upstream of the herpes-simplex-virus thymidine-kinase promoter, the NRE exhibited stimulatory activity in non-beta (BHK) and beta (HIT) cells. The positive activity within the NRE was mapped to a sequence that resembled the binding site for the ubiquitous factor Oct-1. These results indicated that the negative activity of the NRE was dependent on its interaction with other regulatory sites within the insulin gene. Thus, the NRE exhibited negative activity in transfected HIT cells when placed upstream of an insulin gene fragment (positions -261 to +112). However, its activity was modulated in a positive manner by inclusion of additional sequences from position -279 to -341. This region contains the CT3 box that binds the homeodomain protein IUF1 (insulin upstream factor 1). The NRE resembled a silencer, being at least partly independent of precise location and orientation, and being able to operate upon a variety of promoters. The role of the NRE is unclear, although it may be involved in restricting expression of the insulin gene to cells of the islets of Langerhans.

Animals↗

Identification and characterization of a functional retinoic acid/thyroid hormone-response element upstream of the human insulin gene enhancer.

A deletion analysis of the human insulin gene extending to 2 kb upstream of the transcription start site provided evidence of regulatory sequences located upstream of the insulin-linked polymorphic region (ILPR). Within this ILPR-distal region is a sequence (Ink, for insulin kilobase upstream) which contains three potential nuclear hormone-receptor half-sites, closely matching the consensus sequence AGGTCA. These sequences are arranged as a palindromic element with zero spacing over-lapping a direct repeat with 2 bp spacing. The Ink sequence was used in electrophoretic mobility-shift assays within nuclear extracts from COS-7 cells overexpressing the vitamin D, thyroid hormone or retinoic acid receptors, or from an insulin-expressing hamster cell line, HIT-T15. These studies suggest that the insulin-expressing cell line contains thyroid hormone and retinoic acid receptors at least, and that these receptors are able to recognize the Ink sequence. Three copies of the Ink sequence were placed upstream of the thymidine kinase promoter and firefly luciferase reporter gene. In COS-7 cells expressing the appropriate nuclear hormone receptor, this construct was responsive to both thyroid hormone (18-fold) and all-trans-retinoic acid (31-fold). In HIT-T15 cells the same construct responded to all-trans-retinoic acid, but not to thyroid hormone. Within the context of a 2 kb insulin gene fragment, the Ink sequence was shown to be activated by retinoic acid and by the retinoic acid receptor, but acted as a negative element in the presence of both retinoic acid and the retinoic acid receptor. Mutagenesis studies demonstrated that the palindromic sequence was important for the retinoic acid response, and for binding of complexes containing retinoic acid receptor. In human islets of Langerhans, retinoic acid was shown to stimulate insulin mRNA levels. These results demonstrate that a functional nuclear hormone-receptor-response element is located upstream of the human ILPR. As retinoic acid and thyroid hormone are frequently involved in developmental regulatory processes, it is possible that this element may be important in the process of islet cell differentiation.

Animals↗

Intergenic regions between tandem gp63 genes influence the differential expression of gp63 RNAs in Leishmania chagasi promastigotes.

The major surface protease, gp63, of Leishmania chagasi is encoded by 18 or more tandem msp genes that can be grouped into three classes on the basis of their unique 3'-untranslated sequences (3'-UTRs) and their differential expression. RNAs from the mspLs occur predominantly during the logarithmic phase of promastigote growth in vitro, RNAs from the mspSs are present mainly in stationary phase, and RNAs from mspCs occur throughout growth in culture. All three classes of gp63 genes are constitutively transcribed during all growth phases, indicating that their expression is post-transcriptionally regulated. Chimeric plasmids containing the three different 3'-UTRs and downstream intergenic regions (IRs) fused downstream of the beta-galactosidase (beta-gal) coding region were transfected into L. chagasi, and their effects on beta-gal RNA processing and enzymatic activity were examined. The presence of the 3'-UTRs by themselves had no substantive effect on beta-gal expression. However, the 3'-UTR from a mspS plus its IR resulted in about 20-fold more beta-gal activity and RNA in stationary phase relative to logarithmic phase cells. In contrast, the 3'-UTRs plus IRs of mspL and mspC had either no or little effect, respectively, on beta-gal expression. Thus, differential expression of the mspLs and mspSs is post-transcriptionally controlled by different mechanisms.

Animals↗

Developmentally regulated expression of a novel 59-kDa product of the major surface protease (Msp or gp63) gene family of Leishmania chagasi.

All species of Leishmania express a major surface protease (Msp or gp63) that facilitates the interactions of the parasite with its environment at several steps in its life cycle. The msp gene family in Leishmania chagasi contains three classes of genes whose mRNAs are differentially expressed during parasite growth. Logarithmic phase (low infectivity) promastigotes express only 63-kDa versions of Msp, whereas stationary phase (high infectivity) promastigotes express both 63- and 59-kDa Msps. The different migrations of the 59- and 63-kDa proteins on acrylamide gels are not due to differences in N-linked glycosylation or the membrane anchor. Plasmid transfections of Leishmania demonstrate that mspS2 of the stationary gene class encodes a 59-kDa protein. Expression of the 59-kDa protein in stationary phase promastigotes ceases after about 12 weeks of in vitro cultivation when the parasites become attenuated. Attenuated parasites can be stimulated to re-express the 59-kDa Msp by passage through mice followed by several in vitro passages of recovered promastigotes. Amastigotes express yet another subset of Msp proteins. Thus, the 59-kDa product of mspS2 is expressed only in stationary phase promastigotes and only after recent exposure to environmental changes encountered in the mammalian host cell.

Amino Acid Sequence↗

Rapid radiochemical purity testing for [131I]m-iodobenzylguanidine.

The standard high pressure liquid chromatography (HPLC) method for determining radiochemical purity (RCP) of [131I]m-iodobenzylguanidine ([131I]mIBG) is cumbersome and time-consuming. A simplified and rapid separation method with the use of a reverse-phase extraction chromatography technique (i.e. Sep-Pak C18 [SPC] cartridge) is described. The new SPC system closely correlates (r = 0.99) to the standard HPLC method, and the time to complete the SPC analysis is less than 5 min.

3-Iodobenzylguanidine↗

Generator eluate effects on the labeling efficiency of 99mTc-sestamibi.

Our nuclear pharmacy noted that 99mTc-sestamibi kits sometimes failed radiochemical purity (RCP) testing (i.e., RCP < 90%). All failed kits had been prepared with eluate from a newly arrived generator (ingrowth time > or = 72 h) which had been eluted > or = 6 h before the kit failure. The effects of 99mTc activity and eluate volume were then investigated to help explain the reason for the low RCP values. Our results demonstrated that higher failure rates of the 99mTc-sestamibi kits were noted when higher activities of 99mTc eluates were added, and the higher failure rates of the kits were associated with lower RCP values. In addition, higher kit failure rate and lower RCP values of the 5.55-GBq kits at 12 h postelution in comparison with the 11.1-GBq kits at 6 h (same eluate volume) indicated that the 99mTc activity and volume had a less detrimental effect on the 99mTc-sestamibi kit preparation than the 99mTc eluate age. The kit failures might be explained by the higher amount of 99mTc and the production of the free radicals during the long ingrowth time prior to generator elution. In conclusion, the use of a first elution from a long-ingrowth time generator at a later stage (i.e., 11.1 GBq at 6 h and 5.55 GBq at 12 h postelution) in preparation of a 99mTc-sestamibi kit is associated with a high rate of kit failure and should therefore be avoided.

Isotope Labeling↗

Geographic latitude and the efficacy of bacillus Calmette-Guérin vaccine.

In a meta-analysis of the efficacy of BCG vaccine for preventing tuberculosis, study sites at a greater distance from the equator were associated with a higher efficacy. In a random-effects regression analysis of prospective studies, geographic latitude alone accounted for 41% of the between-study variance. Many factors that vary with latitude may influence the effectiveness of BCG vaccine by modifying the susceptibility of human hosts, the pathogenecity of the organism, or host-agent interactions. These factors include socioeconomic conditions, genetic composition of the population, climate, exposure to sunlight, diet and nutrition, presence of nontuberculous mycobacteria in the environment, completeness of surveillance and follow-up in studies of BCG vaccine, virulence of locally prevalent strains of Mycobacterium tuberculosis, and storage and viability of BCG vaccine. This paper describes the biological plausibility, epidemiologic evidence, and other scientific data bearing on the influence of these factors on the efficacy of BCG vaccine.

Animals↗

The interdisciplinary generalist curriculum project: a national medical school demonstration project.

The United States is facing the challenge of producing more generalists for the physician workforce. The Primary Care Organizations' Consortium (PCOC) has responded by focusing on how medical education can be modified to enhance and support medical students' interest in and commitment to generalism early in their training. Evolving from PCOC's developmental work, the five-year Interdisciplinary Generalist Curriculum (IGC) Project was developed to encourage the nation's schools of medicine and colleges of osteopathic medicine to implement interdisciplinary generalist curricula in the preclinical years. Funded by the Division of Medicine in the Bureau of Health Professions of the Health Resources and Services Administration (HRSA), the IGC Project has successfully developed and implemented a nationally competitive medical school demonstration project. Thirty-three schools submitted proposals for an IGC Project award; nine were selected for site visits, from which five were chosen to receive three-year awards. Rigorous attention to creating and maintaining an interdisciplinary focus has characterized the first phase of the IGC Project. Shared leadership among the Executive Committee's project director and two project codirectors and parity in representation among the three disciplines of family medicine, internal medicine, and pediatrics on the Advisory Committee have formed a critical foundation for interdisciplinary functioning within the project. Growing national interest in generalist training and other funding initiatives have contributed to acceptance of the IGC Project. The high level of interest in the IGC Project and the successful interdisciplinary collaboration during the first phase would indicate that the interdisciplinary process can be replicated to move the nation's medical education institutions toward the production of needed generalist physicians.

Curriculum↗

Comparison of four alternative radiochemical purity testing methods for 99Tcm-sestamibi.

Four different methods for determining the radiochemical purity (RCP) of 99Tcm-sestamibi have been proposed to replace the recommended thin-layer chromatography (TLC) method, as the recommended method is inconvenient and time-consuming. The purpose of this study was to compare the recommended TLC method with the four proposed rapid QC methods for 99Tcm-sestamibi: (1) chloroform extraction (CE), (2) mini-paper chromatography with chloroform/tetrahydrofuran (1:1, v/v) (MPC), (3) Waters Sep-Pak alumina N cartridge with 100% ethanol (SPE), and (4) Waters Sep-Pak C18 cartridge with normal saline (SPNS). For RCP values ranging from 21.8 to 98.7% (n = 20), both the CE and SPNS methods produced falsely high RCP values (RCP difference: 14.1 +/- 23.5% for CE and 15.0 +/- 24.9% for SPNS). The MPC and SPE methods were in good agreement (r = 0.98 for MPC and 0.88 for SPE) with the recommended TLC method over the critical RCP range (i.e. 77.0-98.7%, n = 52) (RCP difference: -0.9 +/- 1.2% for MPC and -4.3 +/- 3.2% for SPE). None of the 99Tcm-sestamibi preparations that had been rejected (i.e. RCP < 90%) by the TLC method were accepted by either the MPC or SPE method. However, 4 of the 52 99Tcm-sestamibi preparations with acceptable RCP by the TLC method had unacceptable RCP by the MPC method, whereas 8 of the same 52 preparations were unacceptable by the SPE method.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloroform↗

Gonadotropin-releasing hormone mRNA and gonadotropin beta-subunit mRNA expression in the adult female rat exposed to ethanol in utero.

Previous studies have demonstrated that exposure of female rats to ethanol in utero results in long-term deficits in reproductive function, including a delayed onset of puberty and an early onset of acyclicity. In the present studies, we determined if changes in reproduction are correlated with changes in gonadotropin-releasing hormone (GnRH) mRNA expression in the brain or gonadotropin subunit mRNA expression in the anterior pituitary gland. We used in situ hybridization histochemical techniques to examine the density of GnRH mRNA and the distribution of GnRH mRNA-containing cells in the basal forebrain, and reverse transcription-polymerase chain reaction (RT-PCR) to quantitate the beta-subunit mRNA of luteinizing hormone (LH beta) and follicle-stimulating hormone (FSH beta) in the anterior pituitary gland of adult (3 months of age) fetal alcohol-exposed (FAE) female rats. For GnRH mRNA measurements, animals were gonadectomized 4 days before use. Three groups of animals were examined. FAE females were derived from pregnant dams fed a liquid diet containing 35% ethanol-derived calories from gestational day 14 until parturition. Dams of control animals were either pair-fed (PF) an isocaloric diet with sucrose substituted for ethanol or maintained on normal laboratory rat chow [chow-fed (CF)]. Serial blood samples taken by indwelling right atrial cannulae demonstrated significantly smaller pulses of LH (p < 0.05) and FSH (p < 0.05) in ovariectomized FAE females at 3 months of age, compared with PF and CF controls. Distribution of GnRH mRNA-containing cells was mapped throughout the forebrain, and the number of autoradiographic silver grains/cell was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗