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Biomedical subjects

D M Wilson

Publications and source records attributed to D M Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prospective study of risk factors for the initiation of cigarette smoking.

Risk factors for the initiation of cigarette smoking were examined in 2 consecutive cohorts of teenagers (N = 1,901). Students in Cohort 1 were followed over 4 years from 9th to 12th grade; those in Cohort 2 were followed over 3 years from 9th to 11th grade. Among girls with no history of smoking at baseline, those with more friends who smoked at baseline (p < .001) and those with higher sociability scores (p < .05) were significantly more likely to have tried smoking over the study interval. Among boys with no history of smoking at baseline, those with more friends who smoked at baseline (p < .05) and those with higher depression symptoms scores (p < .01) were significantly more likely to have tried smoking over the study interval. The data suggest that future research is needed to examine potential gender differences that may have implications for the next generation of smoking-prevention programs.

Adolescent↗
PubMed1997

Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes.

Nucleic acid immunization is a novel vaccination technique to induce antigen-specific immune responses. We have developed expression cassettes for cell surface markers CD80 and CD86, two functionally related costimulatory molecules that play an important role in the induction of T cell-mediated immune responses. Coimmunization of these expression plasmids, along with plasmid DNA encoding for HIV-1 antigens, did not result in any significant change in the humoral response; however, we observed a dramatic increase in cytotoxic T-lymphocyte (CTL) induction as well as T-helper cell proliferation after the coadministration of CD86 genes. In contrast, coimmunization with a CD80 expression cassette resulted in a minor, but positive increase in T-helper cell or CTL responses. This strategy may be of value for the generation of rationally designed vaccines and immune therapeutics.

Animals↗
PubMed1997

Folliculotropic mycosis fungoides with large-cell transformation presenting as dissecting cellulitis of the scalp.

Follicular mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL) in which malignant lymphocytes preferentially infiltrate hair follicles. This report describes a patient with follicular mycosis fungoides presenting in a manner similar to dissecting cellulitis of the scalp with nonhealing, draining nodular lesions. Follicular mucinosis associated with folliculotropic mycosis fungoides resulted in follicular disruption and deep dissecting cellulitis. Large-cell transformation of CTCL was present in the initial diagnostic scalp and axillary lymph node specimens. The patient died from progressive CTCL 9 months following initial diagnosis despite electron beam radiation, topical mechlorethamine, interferon-alpha, and systemic chemotherapy. This case indicates that large-cell transformation of folliculotropic mycosis fungoides is an aggressive form of CTCL, and that folliculotropic mycosis fungoides can give rise to lesions which resemble dissecting cellulitis of the scalp. Upregulation of intercellular adhesion molecule-1 (ICAM-1) on follicular epithelium adjacent to lymphocyte function-associated antigen-1 (LFA-1)-positive folliculotropic lymphoma cells in this report provides insight into lymphocyte homing mechanisms in folliculotropic MF.

Adult↗
PubMed1997

Regulation of eukaryotic abasic endonucleases and their role in genetic stability.

Abasic (AP) sites in DNA arise from spontaneous reactions or the action of DNA glycosylases and represent a loss of genetic information. The AP sites can be mutagenic or cytotoxic, and their repair is initiated by class II AP endonucleases, which incise immediately 5' to AP sites. The main enzyme of S. cerevisiae. Apn1, provides cellular resistance to oxidants (e.g., H2O2) or alkylating agents, and limits the spontaneous mutation rate. AP endonucleases from other species can replace Apn1 function in yeast to different extents. We studied the main human enzyme, Ape, with respect to its incision specificity in vitro and the expression of the APE gene in vivo. The results suggest that Ape evolved to act preferentially on AP sites compared to deoxyribose fragments located at oxidative strand breaks and that the incision modes of Ape and Apn1 may be fundamentally different. We also defined the functional APE promoter, and showed that APE expression is transiently downregulated during the regeneration of epidermis after wounding. This latter effect may lead to a window of vulnerability for DNA damage and perhaps mutagenesis during the healing of epidermal and other wounds. Such unexpected effects on the expression of DNA repair enzymes need to be taken into account in analyzing the susceptibility of different tissues to carcinogens.

DNA Damage↗
PubMed1997

Aggravation of polycystic kidney disease in Han:SPRD rats by buthionine sulfoximine.

The administration of ammonium chloride or of sodium or potassium bicarbonate has marked effects on the development of polycystic kidney disease (PKD) in Han:SPRD rats. Because of the possibility that these effects are mediated by changes in redox metabolism, the aim of this study was to determine whether depletion of glutathione, the most abundant and important cellular thiol and scavenger of reactive oxygen species, would affect the development of PKD in this animal model. +/+ and cy/+ Han:SPRD rats were treated with: (1) L-buthionine(S,R)-sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting enzyme for the synthesis of glutathione; (2) glutathione monoethyl ester (GME), a compound that is known to increase the intracellular levels of glutathione; or (3) BSO and GME. Treatment with these drugs was started at 3 wk of age, and the animals were killed at 6 or 8 wk of age. Renal levels of oxidized glutathione were significantly higher in cy/+ than in +/+ rats, whereas no significant differences in reduced glutathione were detected. The administration of BSO caused a marked reduction in the levels of glutathione. The administration of GME caused a significant increase in the levels of glutathione at 2 h, but not at 12 h, after the administration. The increase in the renal levels of glutathione 2 h after the administration of GME was less in the rats treated with BSO than in the rats not receiving this drug, indicating that in part the increase in glutathione level was due to de novo synthesis. BSO-induced glutathione depletion was accompanied by a marked aggravation of the renal cystic disease, as reflected by kidney weights, histological scores, and plasma urea concentrations. However, the administration of GME did not lessen the cystic disease and did not reverse the effects of BSO. The transient effect of GME administration and the simultaneous increases in the levels of cysteine and oxidized glutathione, in addition to reduced glutathione, may explain the lack of protection by GME. These data support the notion that changes in redox metabolism may affect the development of PKD.

Animals↗
PubMed1997

Psychiatric risk associated with early puberty in adolescent girls.

OBJECTIVE: This study prospectively evaluated the relationship between early puberty and the onset of internalizing symptoms and disorders in adolescent girls. METHOD: The sample was drawn from 1,463 sixth-, seventh-, and eighth-grade girls who participated in a longitudinal school-based study of growth and development. Pubertal stage was determined by self-assessment of Tanner stage. Psychiatric assessments included self-report instruments and structured diagnostic interviews. Survival methods were utilized for data analysis. RESULTS: Girls with onset of internalizing symptoms were on average 5 months earlier in pubertal development than those who were asymptomatic (p < .001). In addition, girls with earlier maturation (earliest quartile) were more likely to develop internalizing symptoms than were nonearly matures (hazard ratio = 1.8, confidence interval = 1.2, 2.7). In a subsample of girls followed into high school, early-maturing girls were at marginally higher risk (p < .10) for developing internalizing disorders by the study's end. The highest risk for internalizing disorders was for those girls with both early puberty and prior internalizing symptoms (odds ratio = 3.3). CONCLUSION: Early puberty increases the risk of internalizing symptoms and perhaps internalizing disorders in adolescent girls.

Chi-Square Distribution↗
PubMed1997

Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease.

Alzheimer's disease is a degenerative disorder of the central nervous system, characterized by the concomitant deposition of extracellular filaments composed of beta-amyloid peptides and intracellular filaments composed of the microtubule-associated protein tau. We have discovered that free fatty acids (FFAs) stimulate the assembly of both amyloid and tau filaments in vitro. The minimal concentration of arachidonic acid observed to stimulate tau assembly ranged from 10 to 20 mumol/L, depending on the source of the purified tau. Tau preparations that do not exhibit spontaneous assembly were among those induced to polymerize by arachidonic acid. All long-chain FFAs tested enhanced assembly to some extent, although greater stimulation was usually associated with unsaturated forms. Utilizing fluorescence spectroscopy, unsaturated FFAs were also demonstrated to induce beta-amyloid assembly. The minimal concentration of oleic or linoleic acid observed to stimulate the assembly of amyloid was 40 mumol/L. The filamentous nature of these thioflavin-binding amyloid polymers was verified by electron microscopy. These data define a new set of tools for examining the polymerization of amyloid and tau proteins and suggest that cortical elevations of FFAs may constitute a unifying stimulatory event driving the formation of two of the obvious pathogenetic lesions in Alzheimer's disease.

Alzheimer Disease↗
PubMed1997

Predictors of progression of diabetic nephropathy: implication for timing of kidney transplantation.

Multiple risk factors are important predictors in the development of diabetic nephropathy (DN). Once DN has developed, it progresses steadily to renal failure. To determine the rate of renal function decline and the parameters that influence the rate of decline, we retrospectively reviewed the charts of patients with DN who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983 to 1993. Forty patients were found to have two or more iothalamate clearance (IothmCl) measurements where a slope of renal function decline over time, expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined included age of onset and duration of diabetes (DM); age at initial presentation, insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP), number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine, and initial IothmCl. The mean overall decline of clearance was 1.36 +/- 1.1 mL/min/month, corrected. Univariate regression analysis showed that only systolic and mean BP (p < 0.05), use of HTM (p = 0.02), and the number of HTM used (p = 0.0001) correlated with the rate of clearance decline. No other parameter was significant. The decline of IothmCl was 0.72 +/- 0.41, 1.20 +/- 0.9, and 2.34 +/- 1.38 mL/min/month, for patients taking no HTM, < 3 HTM, and > or = 3HTM, respectively. Of the eight patients on HTM who presented with initial IothmCl of < 30 mL/min/1.73 m2, seven (88%) had clearance of < 10 mL/min/1.73 m2 within 1 yr. We conclude that hypertension is an important marker of DN progression, and that the more HTM required for control of BP, the faster the decline of renal function. We recommend that a suitable transplant candidate with DN who presents with hypertension requiring HTM and a clearance of < 30 mL/min should be placed on the transplant waiting list.

Adult↗
PubMed1996

Somatostatin receptor-binding peptides labeled with technetium-99m: chemistry and initial biological studies.

The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (Ki's in the 0.25 - 10 nM range) compared favorably with [DTPA]octreotide (Ki = 1.6 nM), which, as the indium-111 complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a Ki's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The 99m Tc-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.

Amino Acid Sequence↗
PubMed1996

Thrombus imaging using technetium-99m-labeled high-potency GPIIb/IIIa receptor antagonists. Chemistry and initial biological studies.

Platelet-specific compounds which are radiolabeled with gamma-emitting radionuclides may be particularly useful for the noninvasive in vivo detection of thrombi. The synthesis of peptides which are potent inhibitors of platelet aggregation and which contain a chelator for the radionuclide technetium-99m are described. The target compounds were designed such that stable, oxotechnetium(V) species could be prepared where the site of metal coordination was well defined. A strategy was employed where the pharmacophore-Arg-Gly-Asp-(RGD), or RGD mimetic, was constrained in a ring which was formed by the S-alkylation of a cysteine residue with an N-terminal chloroacetyl group. Binding affinities were enhanced by the replacement of arginine with the arginine mimetics S-(3-aminopropyl)cysteine and 4-amidinophenylalanine. Further enhancements could be obtained by the synthesis of oligomers which contained two or more rings containing receptor binding regions. The increase in binding affinity seen was more than that expected from a simple stoichiometric increase of pharmacophore. The most potent compounds described had IC50s of approximately 0.03 microM for the inhibition of human platelet aggregation. Two of the more potent peptides (P280 and P748) were labeled with technetium-99m and assessed in a canine thrombosis model. The 99m Tc complexes of the peptides prepared in this work hold promise as thrombus imaging agents due to their high receptor binding affinity, ease of preparation, and expected rapid pharmacokinetics.

Amino Acid Sequence↗
PubMed1996

Development of greenhouse screening for resistance to Aspergillus parasiticus infection and preharvest aflatoxin contamination in peanut.

Aspergillus flavus Link ex Fries and A. parasiticus Speare can invade peanut kernels and under certain environmental conditions produce unacceptable levels of the mycotoxin aflatoxin. A concerted effort is underway to reduce aflatoxin contamination in peanut and peanut products. A potentially effective method of control in peanut is the discovery and use of genes for resistance to either fungal invasion or aflatoxin formation. The objective of the present experimental study was to develop an effective and efficient procedure for screening individual plants or pods of single plants for resistance to invasion by the aflatoxigenic fungi and subsequent aflatoxin production. Methods of obtaining adequate drought-stress and fungal infection were developed through this series of experiments. By completely isolating the pods from the root zone and imposing drought-stress only on pegs and pods, high levels of fungal infection were observed. High amounts of preharvest aflatoxin accumulation were also produced by completely isolating the pods from the root zone. Mid-bloom inoculation with A. parasiticus-contaminated cracked corn and drought-stress periods of 40 to 60 days were the most effective procedures. This technique was used to assess peanut genotypes previously identified as being partially resistant to A. parasiticus infection or aflatoxin contamination, and segregating populations from four crosses. Variability in aflatoxin contamination was found among the 11 genotypes evaluated, however, none were significantly lower than the standard cultivars. Broad-sense heritability of four crosses was estimated through evaluation of seed from individual plants in the F2 generation. The heritability estimates of crosses GFA-2 x NC-V11 and Tifton-8 X NC-V11 were 0.46 and 0.29, respectively, but mean aflatoxin contamination levels were high (73,295 and 27,305 ppb). This greenhouse screening method could be an effective tool when genes for superior aflatoxin resistance are identified.

Aflatoxins↗
PubMed1996

Ethnicity and body dissatisfaction: are Hispanic and Asian girls at increased risk for eating disorders?

PURPOSE: To compare prevalences and correlates of body dissatisfaction among white, Hispanic, and Asian girls. METHODS: A total of 939 6th and 7th grade girls (mean age 12.4 years) attending four middle schools in northern California completed self-administered assessments of age, ethnicity, desired body shape, parent education levels, mother's and father's body shapes, pubertal stage, and body dissatisfaction. Body dissatisfaction was assessed with the Body Dissatisfaction scale of the Eating Disorder Inventory. Height, weight, triceps skinfold thickness, and waist and hip circumferences were measured by trained examiners. RESULTS: Hispanic girls reported significantly greater body dissatisfaction than white girls, with Asian girls in-between. After adjustment for body mass index (weight/height), normal and overweight white, Hispanic, and Asian girls reported similar levels of body dissatisfaction. However, among the leanest 25% of girls, Hispanics and Asians reported significantly more body dissatisfaction than white girls. Body mass index was the strongest independent predictor of increased body dissatisfaction in all three ethnic groups. Shorter height among white girls and taller height among Asian girls also made significant independent contributions. Parent education level, a measure of socioeconomic status, was not significantly associated with body dissatisfaction. CONCLUSIONS: Body dissatisfaction is not limited to white girls in middle and upper socioeconomic strata. These findings suggest Hispanic and Asian girls may be at greater risk for adopting eating disorder behaviors than previously recognized.

Adolescent↗
PubMed1996

Weight concerns influence the development of eating disorders: a 4-year prospective study.

The authors examined factors prospectively associated with age of onset of partial syndrome eating disorders over a 4-year interval in a community sample (N = 877) of high school-age adolescent girls. Four percent developed a partial syndrome eating disorder over the interval. A measure of weight concerns was significantly associated with onset in a multivariate Cox proportional hazard analysis (p < .001). Girls scoring in the highest quartile on the measure of weight concerns had the highest incidence (10%) of partial syndrome onset, whereas none of the girls in the lowest quartile developed eating disorder symptoms. This finding is consistent with both theoretical and clinical perspectives and may represent a useful step toward the establishment of a rational basis for the choice of a prevention intervention target.

Adolescent↗
PubMed1996

In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections.

The Upjohn oxazolidinones, U-100592 and U-100766, are orally bioavailable synthetic antimicrobial agents with spectra of activity against antibiotic-susceptible and -resistant gram-positive pathogens. In several mouse models of methicillin-resistant Staphylococcus aureus infection, U-100592 and U-100766 yielded oral 50% effective doses (ED50) ranging from 1.9 to 8.0 mg/kg of body weight, which compared favorably with vancomycin subcutaneous ED50 values of 1.1 to 4.4 mg/kg. Similarly, both compounds were active versus a Staphylococcus epidermidis experimental systemic infection. U-100592 and U-100766 effectively cured an Enterococcus faecalis systemic infection, with ED50 values of 1.3 and 10.0 mg/kg, and versus a vancomycin-resistant Enterococcus faecium infection in immunocompromised mice, both drugs effected cures at 12.5 and 24.0 mg/kg. Both compounds were exceptionally active in vivo against penicillin- and cephalosporin-resistant Streptococcus pneumoniae, with ED50 values ranging from 1.2 to 11.7 mg/kg in systemic infection models. In soft tissue infection models with S. aureus and E. faecalis, both compounds exhibited acceptable curative activities in the range of 11.0 to 39.0 mg/kg. U-100766 was also very active versus the Bacteroides fragilis soft tissue infection model (ED50 = 46.3 mg/kg). In combination-therapy studies, both U-100592 and U-100766 were indifferent or additive in vivo against a monomicrobic S. aureus infection in combination with other antibiotics active against gram-positive bacteria and combined as readily as vancomycin with gentamicin in the treatment of a polymicrobic S. aureus-Escherichia coli infection. U-100592 and U-100766 are potent oxazolidinones active against antibiotic-susceptible and -resistant gram-positive pathogens in experimental systemic and soft tissue infections.

Acetamides↗
PubMed1996

Values and Canadian health care: an Alberta exploration.

In March 1994, a health care conference was held in Edmonton, Alberta, at which the values of conference participants towards health care were systematically recorded and analysed. This exploration is significant because the values that underpin the structure of the current publicly-funded and administered Canadian health care system rarely enter current discussions regarding health care system reform. Rather, economic and other sociopolitical forces now seem to be having a major impact on plans and actual changes within the health care system. Thus, the underlying attitudes and beliefs of Canadians towards health care have not been articulated or given due credence. The conference participants identified three dominant values: (1) the dignity of the human person as an individual and social being; (2) respect for pluralism and difference; and (3) accountability. These values were found to be robust, in that they sustain a focus on the 'common good'. The common good is the core of the Canadian health care system, and is enshrined in the 1984 Canada Health Act. Conceptually, these values could also lead to significant changes in health care, in keeping with the common good, particularly those changes focusing on the current deficiencies of the Canadian health care system.

Attitude to Health↗
PubMed1996

Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and -5, but not IGF-II or IGFBP-4.

Osteoarthritis is a disease in which articular cartilage metabolism is altered, leading to cartilage destruction. As insulin-like growth factor-I (IGF-I) is the major anabolic mediator for articular cartilage, and the IGF-binding proteins (IGFBPs) are an integral part of the IGF axis, they may play a role in the pathophysiology of osteoarthritis. Chondrocytes isolated from fibrillated and normal appearing areas of osteoarthritic human cartilage and from normal cartilage were studied for IGF and IGFBP expression. IGF and IGFBP messenger ribonucleic acids were analyzed by a RT-quantitative PCR technique and Northern blotting. In osteoarthritic chondrocytes, IGF-I message was increased 3.5-fold, IGFBP-3 was increased 24-fold, and IGFBP-5 was increased 16-fold over normal chondrocytes. Chondrocytes from normal appearing areas of cartilage from osteoarthritic joints had intermediate levels. Message levels for beta-actin, IGF-II, and IGFBP-4 were unchanged between the cartilage types. IGF and IGFBP production were analyzed by Western ligand blots and RIAs of conditioned medium from cartilage cultured in serum-free conditions. IGF-I was undetectable in conditioned medium from normal cartilage and increased in that from osteoarthritic cartilage. Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5. IGFBP-2, -3, and -5 production was increased in osteoarthritic cartilage. Proteases with activity against IGFBP-3 and -5 were also produced by osteoarthritic cartilage. The observation that IGFBP-3 and -5 expression and production are elevated in osteoarthritic cartilage suggests that they may be acting as a competitor for IGF-I in osteoarthritic cartilage, thus reducing the anabolic stimulation of this tissue and contributing to the net loss of cartilage in this disease.

Aged↗
PubMed1996

A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty.

OBJECTIVE: We compared a rapid, subcutaneous (SQ), single-sample gonadotropin-releasing hormone (GnRH) stimulation test with the standard multiple-sample, intravenous (IV) GnRH stimulation test used in the evaluation of central precocious puberty (CPP). METHODS: We evaluated 22 patients presenting with evidence of precocious puberty. GnRH (100 microg) was administered subcutaneously in the clinic setting with single serum luteinizing hormone (LH) measured 40 minutes after injection. A standard IV GnRH stimulation test was performed within 2 weeks, with serum LH obtained at 0, 20, 40, and 60 minutes. LH was assayed by immunochemiluminometric assay. RESULTS: The mean peak LH levels after IV and SQ testing were identical. A significant correlation (r = .88) was found between the LH determined by SQ stimulations and the peak LH determined by IV GnRH testing. CPP was diagnosed (LH, >/- 8 IU/L) by both SQ and IV testing in 7 of 22 patients and was excluded by both tests in 14 of 22 patients. A diagnostic discrepancy between peak IV and SQ results was seen in 1 patient. CONCLUSIONS: We conclude that mean GnRH-stimulated LH levels from rapid SQ and standard IV testing are indistinguishable and that individual LH levels by each method are strongly correlated. A rapid SQ GnRH test is a valid tool for laboratory confirmation of CPP.

Age Determination by Skeleton↗