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Biomedical subjects

C McBride

Publications and source records attributed to C McBride.

At least 19 recordsLinked to original sources
PubMed2003

Quantifying levels of transplanted murine and human mesenchymal stem cells in vivo by real-time PCR.

BACKGROUND: Previously, we demonstrated that murine mesenchymal stem cells (MSCs) injected intracranially into mice expand throughout the central nervous system (CNS). This paper describes real-time PCR (RT-PCR) assays that enables accurate quantification of transplanted cells in vivo. METHODS: RT-PCR assays that amplify sequences in the mouse Y chromosome or human Alu repeats were developed and used to quantify the number of male, murine, or human MSCs in the CNS at various times after intracranial injection into neonatal mice, or in various organs of adult mice after i.p. injection of cells into 3 day-old embryos. RESULTS: In the CNS, levels of male mouse DNA in female transplant recipients increased on average 30-fold between 3 and 60 days post-injection but then was unchanged at 140 days post-transplant (P = 0.107). Male DNA accounted for up to 0.309% of the total DNA content of the brain, representing maximally 600000 donor cells. Human DNA was detected in the CNS up to 300 days post-transplant, but levels never exceeded 7.63 x 10 (-4) % of the total brain content. After in utero transplantation, human DNA levels ranged from 0.36 x 10(-5) % to 2.14 x 10 (-5) % of the total DNA content of liver, kidney and spleen. significantly higher levels were found in heart (P = 0.06), femur and brain (P = 0.0025). DISCUSSION: RT-PCR assays were developed to quantify levels of male, murine and human cells in vivo following sex-mismatched or xeno-transplants. Due to their accuracy, precision, and sensitivity, these assays provide a versatile alternative to measuring stem-cell engraftment in vivo.

Adult↗
PubMed2003

Scorpion envenomations in young children in central Arizona.

INTRODUCTION: Centruroides sculpturatus, also known as Centruroides exilicauda or bark scorpion, is the only scorpion native to the United States whose venom produces a potentially life-threatening illness, particularly in children. OBJECTIVES: To describe the distribution of the severity grades following scorpion envenomations, the onset of clinical signs and symptoms, the time to deterioration, and side effects of antivenom treatment in children < or = 2 yrs of age. METHODS: Prospective case-series with the following inclusion criteria of presumed scorpion envenomation, witnessed scorpion or signs and symptoms consistent with envenomation, patient age < or = 2 yrs, and the call was received by the poison center. After data were entered prospectively, a reviewer who was blinded as to the purpose of the study reviewed the charts. A second reviewer examined 10% of the charts for accuracy in coding. Envenomation severity grades were based on a previously described scorpion grading scale and were correlated with admission rates, clinical deterioration, and outcomes. Descriptive statistics (STATA & EXCEL) were used. RESULTS: Of the 491 charts, 483 (98%) had adequate information available. The mean age was 20.8 [range 2-24] months with 133 patients (27.5%) presenting to an emergency department (ED), 86 patients (17.8%) received antivenom, and 25 patients (5.2%) were admitted. The p-value for kappa and the 95% confidence interval (CI) for interobserver reliability kappa score was 0.69 with CI (0.44-0.95). The grade distributions were Grade I = 343 cases (71%), Grade II = 8 cases (1.7%), Grade III = 49 cases (10.1%), and Grade IV = 83 cases (17.2%). The mean time to advancement of grade was 14 min (95% CI [10.97,17.06], 99% CI [10.04,18.03]) and the median time was < 1 min (range 0-140 min). Twenty-five patients (5.2%) were admitted, of which 13 were Grade III and 12 were Grade IV. Three patients (0.6% of total), all Grade IV envenomations, were intubated (95% CI [0.0021-0.0181] or an upper limit of 8.7 patients). Antivenom was administered to 86 patients (17.8%). The mean time of abatement of symptoms following antivenom was 31 [95% CI 10-82] min vs. 22.2 h [95% CI 12-46]. There was one acute reaction (rash) to antivenom administration and 49 cases (57%) of serum sickness. CONCLUSIONS: Clinical progression following scorpion envenomation in children < or = 2 yrs old occurred on average within 14 min of envenomation with onset almost immediately. Serum sickness occurred in 57% of toddlers receiving antivenom and typically lasted less than 3 days. Admissions were less common among patients receiving antivenom.

Antivenins↗
PubMed2001

Isotropic-nematic phase transition: Influence of intramolecular flexibility using a fused hard sphere model.

The role of flexibility on the liquid crystal isotropic-nematic phase transition has been studied by means of Monte Carlo simulation. We present equations of state for the isotropic-nematic branches and, in the isotropic phase, numerically calculated values for the virial coefficients B2, B3, and B4. We have studied two models: 11 hard sphere monomers fused in a linear configuration with a reduced bond length of 0.6 and a 15-monomer version of this model in which monomers at one end of the chain become flexible. We have observed spontaneous nematic liquid crystal formation for both of the fully rigid models, and also for models with up to six flexible monomers in the tail. We conclude that molecular flexibility has a strongly destabilizing effect on the nematic phase. This is probably due to the decrease in shape anisotropy that flexible tails allow.

Journal Article↗
PubMed2001

Adolescent HMO enrollees' utilization of out-of-plan services.

PURPOSE: To examine use of reproductive health services, correlates of out-of-plan care, and reasons for seeking out-of-plan care among adolescent health maintenance organization (HMO) enrollees. METHODS: We mailed a self-administered questionnaire to a population-based random sample of 18-year-old members of Group Health Cooperative of Puget Sound (GHC) who had been enrolled for at least 12 months. The sample was selected from GHC's computerized enrollment database. Questionnaire topics included reproductive history, sexual behavior, and use of health services. Analysis included Chi-square tests to examine differences by gender and out-of-plan status and multivariate analysis using logistic regression. RESULTS: About one-half of the 997 respondents (69% response rate) reported using out-of-plan care. In multivariate analysis, the strongest correlate of out-of-plan care was having had sexual intercourse [odds ratio (OR) = 1.84; 95% confidence interval (CI) = 1.35-2.52]. Other correlates were using alcohol (OR = 1.79; 95% CI = 1.29-2.48), living with parents (OR = 0.65; 95% CI =.46-.92), and being female (OR = 1.60; 95% CI = 1.21-2.11). During the prior year, over 80% of sexually active respondents had obtained contraceptives out-of-plan and 45% of those tested for sexually transmitted diseases (STDs) reported out-of-plan testing. The primary reasons reported for using any out-of-plan care were lack of convenience (28%), being out of town (26%), and confidentiality (23%; only reported by sexually active respondents). CONCLUSIONS: A substantial proportion of GHC-enrolled adolescents used out-of-plan care. Those who did were more likely to have had STDs and other health problems than those who used only in-plan services. Without continuity of care, these at-risk adolescents may not be receiving optimal services.

Adolescent↗
PubMed2001

Motivation for smoking cessation among pregnant women.

The authors evaluated an expanded measure of intrinsic and extrinsic motivation for smoking cessation in a population-based sample of 897 pregnant smokers (500 current smokers and 397 recent quitters). The measure assessed motivation related to pregnancy and parenthood in addition to general intrinsic and extrinsic dimensions. Current smokers at baseline who quit smoking by 28 weeks of pregnancy (n = 102) had significantly higher baseline levels of pregnancy-related motivation than continuing smokers. Extrinsic and pregnancy motivation dropped between baseline and 28 weeks of pregnancy among continuing smokers. Higher levels of intrinsic relative to extrinsic motivation at baseline were associated with sustained abstinence during the first 2 months postpartum. Results suggest that both general and pregnancy-specific motivation are important for smoking cessation and relapse prevention during pregnancy. Interventions to enhance the salience of health benefits over and above those related to pregnancy and other intrinsic benefits of a greater sense of self-control could protect against postpartum relapse.

Female↗
PubMed2001

Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans.

The Toll-like receptor 4 protein acts as the transducing subunit of the lipopolysaccharide receptor complex and assists in the detection of Gram-negative pathogens within the mammalian host. Several lines of evidence support the view that variation at the TLR4 locus may alter host susceptibility to Gram-negative infection or the outcome of infection. Here, we surveyed TLR4 sequence variation in the complete coding region (2.4 kb) in 348 individuals from several population samples; in addition, a subset of the individuals was surveyed at 1.1 kb of intronic sequence. More than 90% of the chromosomes examined encoded the same structural isoform of TLR4, while the rest harbored 12 rare amino acid variants. Conversely, the variants at silent sites (intronic and synonymous positions) occur at both low and high frequencies and are consistent with a neutral model of mutation and random drift. The spectrum of allele frequencies for amino acid variants shows a significant skew toward lower frequencies relative to both the neutral model and the pattern observed at linked silent sites. This is consistent with the hypothesis that weak purifying selection acted on TLR4 and that most mutations affecting TLR4 protein structure have at least mildly deleterious phenotypic effects. These results may imply that genetic variants contributing to disease susceptibility occur at low frequencies in the population and suggest strategies for optimizing the design of disease-mapping studies.

Alleles↗
PubMed2001

The effect of neighborhood-based community organizing: results from the Seattle Minority Youth Health Project.

OBJECTIVE: To evaluate the effect of a community mobilization and youth development strategy to prevent drug abuse, violence, and risky sexual activity. DATA SOURCES/STUDY SETTING: Primary surveys of youth, parents, and key neighborhood leaders were carried out at baseline (1994) and at the end of the intervention period (1997). The study took place in four intervention and six control neighborhoods in Seattle. STUDY DESIGN: The study was designed as a randomized controlled trial with neighborhood as the unit of randomization. The intervention consisted of a paid community organizer in each neighborhood who recruited a group of residents to serve as a community action board. Key variables included perceptions of neighborhood mobilization by youth, parents, and key neighborhood leaders. DATA COLLECTION/EXTRACTION METHODS: Youth surveys were self-administered during school hours. Parent and neighborhood leader surveys were conducted over the phone by trained interviewers. PRINCIPAL FINDINGS: Survey results showed that mobilization increased to the same degree in both intervention and control neighborhoods with no evidence of an overall intervention effect. There did appear to be a relative increase in mobilization in the neighborhood with the highest level of intervention activity. CONCLUSION: This randomized study failed to demonstrate a measurable effect for a community mobilization intervention. It is uncertain whether the negative finding was because of a lack of strength of the interventions or problems detecting intervention effects using individual-level closed-end surveys.

Adolescent↗
PubMed2000

Phylogenetic variation and polymorphism at the toll-like receptor 4 locus (TLR4).

BACKGROUND: Differences in responses to bacterial surface lipopolysaccharides (LPSs) are apparent between and within mammalian species. It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene (Tlr4), the product of which is thought to bind LPS and mediate LPS signal transduction in immune system cells. RESULTS: We have sequenced the Toll-like receptor 4 gene of humans (TLR4; 19.0 kilobases, kb) and mice (Tlr4; 91.7 kb), as well as the coding region and splice junctions of Tlr4 from 35 mouse (Mus musculus) strains, from the chimpanzee and from the baboon. No other discernible genes or regions of interspecies conservation lies close to Tlr4 and, in both humans and mice, flanking sequences and introns are rich in repeats of retroviral origin. Interstrain analyses reveal that Tlr4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, both among strains and among species. The cytoplasmic domain of the Tlr4 protein is highly variable at the carboxy-terminal end. CONCLUSIONS: We suggest that selective evolutionary pressure exerted by microbes expressing structurally distinguishable LPS molecules has produced the high level of variability in the Tlr4 extracellular domain. The highly variable carboxy-terminal region of the cytoplasmic domain is likely to determine the magnitude of the response to LPS within a species.

Animals↗
PubMed2000

Current health behaviors and readiness to pursue life-style changes among men and women diagnosed with early stage prostate and breast carcinomas.

BACKGROUND: Cancer survivors are at increased risk for developing secondary tumors, diabetes, osteoporosis, and cardiovascular disease, thus making them an important target population for health-related interventions. However, little is known regarding cancer survivors' behaviors and their interest in pursuing healthier diets, exercise, and smoking cessation. METHODS: A 65-item survey was mailed to 1667 patients diagnosed with early stage carcinoma of the breast or prostate that requested data regarding demographics, health behaviors, stage of readiness for smoking cessation, exercise, increased fruit and vegetable (F&V) consumption, and decreased fat intake, as well as interest in specific health programs and when, relative to diagnosis, these programs should be offered. RESULTS: Responses from 978 cancer survivors suggested that the overwhelming majority (85%) reported their health as good to excellent. The majority of respondents (55%) ate fewer than 5 daily servings of F&Vs, with prostate carcinoma patients reporting eating significantly fewer servings than patients with breast carcinoma (P < 0.001). In contrast, 69% of respondents reported adherence to a low fat diet, again with lower practice rates among prostate carcinoma patients than patients with breast carcinoma (P = 0.006). The majority of respondents (58%) reported routine exercise and 8% were current smokers. Significantly more breast carcinoma patients than prostate carcinoma patients were current smokers (P = 0.03). There was strong interest in health promotion programs across behaviors, and a fair amount of concordance between low fat dietary behaviors and exercise, as well as consumption of five daily servings of F&Vs. The majority of patients expressed a preference for programs that could be delivered via mailed brochure, with 57% of respondents indicating that programs should be initiated at the time of diagnosis or soon after (within 6 months). CONCLUSIONS: The results of the current study suggest that although many cancer survivors already practice healthy life-style behaviors, there is a substantial proportion who do not. Interventions especially are needed to increase daily F&V intake; however, given the fair degree of clustering between dietary and exercise behaviors, multiple risk factor interventions also may be warranted. Among cancer survivors, receptivity is high for health promotion programs, especially those that can be delivered by mail and soon after diagnosis.

Adult↗
PubMed2000

Feasibility of a tailored intervention to improve preventive care use in women.

BACKGROUND: Women age 50 years and older are in need of multiple preventive health care services. Despite recent improvements in rates of delivery of preventive care services, especially within managed care organizations, substantial numbers of women are still being underscreened. Efforts to improve delivery of preventive care services have often focused on one outstanding service despite the fact that patients often are in need of many services. METHODS: A total of 893 women age 50 to 55 years were mailed a self-administered survey to identify outstanding preventive health care service needs. Patients in need of three or more outstanding preventive health care services were identified from survey respondents to participate in a feasibility study evaluating a tailored, customized intervention called Tic Tac Health. RESULTS: Five-hundred ninety-one women returned the survey (67%). Four-hundred forty-eight (76%) women were in need of one or more preventive health services; 92 (16%) were in need of three or more. Twenty-two patients (24%) completed the Tic Tac Health card. The women who completed the card were similar to those who did not. CONCLUSIONS: Despite documented physician visits, presence of managed care health insurance, and a designated primary care provider, a significant number of women are still in need of multiple preventive health services. An intervention targeting multiple preventive health services was demonstrated to be both feasible and effective. Further evaluation via a randomized controlled trial should be conducted to determine if an intervention like Tic Tac Health would be an effective modality for improving rates of receipt of multiple preventive health care services.

Adult↗
PubMed1999

The association between cigarette smoking and low-grade cervical abnormalities in reproductive-age women.

OBJECTIVE: To evaluate the association between smoking and the occurrence of low-grade cervical cytological abnormalities. METHODS: We conducted a population-based cross-sectional study of smoking and other exposures in reproductive-age women with normal and abnormal cytology results (Class 1-4 Pap tests). Participants (n = 2,448) were enrollees of the Group Health Cooperative of Puget Sound, a health maintenance organization (HMO) in Washington state, USA. Non-pregnant women were selected monthly from the HMO's cytology database during 1995-6, with over-sampling of women with low-grade abnormalities. All participants completed a structured telephone-administered survey. RESULTS: Of the 2,448 participants, 19% (n = 465) had Class 2 Pap results, and 5% (n = 117) had Class 3-4 results. Forty percent of the sample (n = 975) reported ever smoking. Women reporting current/recent smoking (n = 514, 21%) had an increased likelihood of cervical abnormalities (adjusted odds ratio (OR) 1.4, 95% confidence interval (CI 1.1-1.8). Women who had never smoked but who reported recent passive smoking exposure also had a greater likelihood of abnormal test results (OR 1.4, 95% CI 1.0-2.0). Prior smoking was not associated with cytology status. CONCLUSIONS: Our results, examining low-grade cervical abnormalities, are compatible with those from studies of more severe cervical lesions, lending added support to the hypothesis that smoking predisposes to development of a spectrum of cervical abnormalities. Thus, even cytologic screening visits represent an opportunity to counsel women smokers about their health risks, particularly the more proximal risks of cervical abnormalities and cancer.

Adolescent↗
PubMed1998

Endothelium-dependent relaxation and hyperpolarization in guinea-pig coronary artery: role of epoxyeicosatrienoic acid.

1. Acetylcholine (ACh) elicits an endothelium-dependent relaxation and hyperpolarization in the absence of nitric oxide (NO) and prostaglandin synthesis in the guinea-pig coronary artery (GPCA). This response has been attributed to a factor termed endothelial-derived hyperpolarizing factor (EDHF). Recently it has been suggested that EDHF may be a cytochrome P450 product of arachidonic acid (AA) i.e., an epoxyeicosatrienoic acid (EET). The present study investigated whether this pathway could account for the response to ACh observed in the GPCA in the presence of 100 microM N(omega)-nitro-L-arginine and 10 microM indomethacin. 2. ACh, AA and 11,12-EET each produced concentration-dependent relaxations in arteries contracted with the H1-receptor agonist AEP (2,2-aminoethylpyridine). The AA-induced relaxation was significantly enhanced in the presence of the cyclo-oxygenase/lipoxygenase inhibitor, eicosatetranynoic acid (30 microM). 3. The cytochrome P450 inhibitors proadifen (10 microM) and clotrimazole (10 microM) inhibited ACh, lemakalim (LEM) and AA-induced relaxation, whereas 17-octadecynoic acid (100 microM) and 7-ethoxyresorufin (10 microM) were without effect on all three vasodilators. Proadifen and clotrimazole also inhibited ACh (1 microM) and LEM (1 microM)-induced hyperpolarization. 4. The ability of various potassium channel blockers to inhibit relaxation responses elicited with ACh, AA and 11,12-EET was also determined. Iberiotoxin (IBTX; 100 nM) was without effect on responses to ACh but significantly reduced responses to both AA and 11,12-EET. In contrast, 4-aminopyridine (4-AP; 5 mM) significantly reduced response to ACh but not responses to AA and 11,12-EET. Combined IBTX plus (4-AP) inhibited the ACh-induced relaxation to a greater extent than 4-AP alone. Apamin (1 microM), glibenclamide (10 microM) and BaCl2 (50 microM) had no significant effect on responses to ACh, AA and 11,12-EET. 5. IBTX (100 nM) significantly reduced both 11,12-EET (33 microM) and AA (30 microM) hyperpolarization without affecting the ACh (1 microM)-induced hyperpolarization. In contrast, 4-AP significantly reduced the ACh-induced hyperpolarization without affecting either AA or 11,12-EET-induced hyperpolarizations. 6. In summary, our results suggest that the coronary endothelium releases a factor upon application of AA which hyperpolarizes the smooth muscle. The similarity of pharmacology between AA and 11,12-EET suggests that this factor is an EET. However, the disparity of pharmacology between responses to ACh versus responses to 11,12-EET do not support the hypothesis that EETs represent the predominant factor which ACh releases from the endothelium that leads to NO- and prostaglandin-independent hyperpolarization and relaxation in the GPCA.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Measuring community mobilization in the Seattle Minority Youth Health Project.

This article assesses the validity and reliability of the approach used to measure community mobilization in the Seattle Minority Youth Health Project (MY Health), a neighborhood-based program to prevent drug use, violence, teen pregnancy, and sexually transmitted diseases (STDs). Two constructs were measured: neighborhood cooperation in solving problems, and sense of pride and identification with the neighborhood. The convergent validity of the measurement approach was assessed by comparing several independent measures of community mobilization generated from surveys of key neighborhood leaders, youth, and parents. For the neighborhood cooperation construct, correlations were uniformly positive across measures from different surveys and statistically significant about a quarter of the time. The correlations for the neighborhood pride construct were weaker and generally not statistically significant. Interrater reliability was low for all of the surveys, possibly reflecting varying ideas about what community mobilization meant among survey respondents.

Adolescent↗
PubMed1998

Same-sex and opposite-sex best friend interactions among high school juniors and seniors.

Eighteen adolescents were videotaped during same-sex and opposite-sex interactions in the eleventh and twelfth grades. In both grades, females felt more comfortable during same-sex interactions than during opposite-sex interactions, and they rated their same-sex partners more positively than did males. Females in both grades and males in eleventh grade showed more peer intimacy than did males in twelfth grade. Eleventh-grade females showed the most playful behaviors (the most engaged state). More synchrony (matching of behavior) was found for the animated state in the twelfth grade as compared with the eleventh grade.

Adolescent↗
PubMed1997

BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing.

CONTEXT: A mutation in the BRCA1 gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between risk factors and mutations is incomplete. OBJECTIVES: To identify BRCA1 mutations and to determine factors that best predict presence of a deleterious BRCA1 mutation in patients with breast and/or ovarian cancer. DESIGN: A complete sequence analysis of the BRCA1 coding sequence and flanking intronic regions was performed in 798 women in a collaborative effort involving institutions from the United States, Italy, Germany, Finland, and Switzerland. PARTICIPANTS: Institutions selected 798 persons representing families (1 person for each family) thought to be at elevated a priori risk of BRCA1 mutation due to potential risk factors, such as multiple cases of breast cancer, early age of breast cancer diagnosis, and cases of ovarian cancer. No participant was from a family in which genetic markers showed linkage to the BRCA1 locus. MAJOR OUTCOME MEASURES: Sequence variants detected in this sample are presented along with analyses designed to determine predictive characteristics of those testing positive for BRCA1 mutations. RESULTS: In 102 women (12.8%), clearly deleterious mutations were detected. Fifty new genetic alterations were found including 24 deleterious mutations, 24 variants of unknown significance, and 2 rare polymorphisms. In a subset of 71 Ashkenazi Jewish women, only 2 distinct deleterious mutations were found: 185delAG in 17 cases and 5382insC in 7 cases. A bias in prior reports for mutations in exon 11 was revealed. Characteristics of a patient's specific diagnosis (unilateral or bilateral breast cancer, with or without ovarian cancer), early age at diagnosis, Ashkenazi Jewish ethnicity, and family history of cancer were positively associated with the probability of her carrying a deleterious BRCA1 mutation. CONCLUSIONS: Using logistic regression analysis, we provide a method for evaluating the probability of a woman's carrying a deleterious BRCA1 mutation for a wide range of cases, which can be an important tool for clinicians as they incorporate genetic susceptibility testing into their medical practice.

Breast Neoplasms↗
PubMed1997

Child psychiatric patients' interactions with their mothers.

This study investigated whether child psychiatric patients' and their mothers interacted differently as a function of whether the children were diagnosed as having internalizing or externalizing disorders. Twenty children and their mothers were rated on eight behavior dimensions as they engaged in a ten-minute play session. Maternal depression was found to interact with their children's diagnoses and behavioral ratings.

Adult↗