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Biomedical subjects

Lisa Miller

Publications and source records attributed to Lisa Miller.

At least 19 recordsLinked to original sources
PubMed2006

Vascular remodeling is airway generation-specific in a primate model of chronic asthma.

RATIONALE: Changes in the density of bronchial vessels have been proposed as a part of airway remodeling that occurs in chronic asthma. OBJECTIVES: Using an established nonhuman primate model of chronic allergic asthma, we evaluated changes in vascular density as well as the contribution of bronchial epithelium to produce vascular endothelial growth factor (VEGF). METHODS: Eight juvenile rhesus macaques were divided into two groups of four. One group was exposed to 11 cycles of aerosolized house dust mite allergen (HDMA), whereas the other was exposed to filtered air. Bronchial wall vasculature was identified using an immunohistochemical approach, and vascular density was quantified stereologically. A semiquantitative polymerase chain reaction approach was used to estimate VEGF splice variant gene expression at discrete airway generations. Cell culture of primary tracheal epithelial cells with varying concentrations of HDMA was used to quantify the direct contribution of the epithelium to VEGF production. RESULTS: Bronchial vascular density was increased at mid- to lower airway generations, which was independent of changes in the interstitial compartment. The VEGF121 splice variant was significantly increased at lower airway generations. VEGF protein increased in a dose-dependant fashion in vitro primarily by an increase in VEGF121 gene expression. CONCLUSION: This study highlights that increased vascular density in an animal model of chronic allergic asthma is airway generation specific and associated with a unique increase of VEGF splice variant gene expression. Airway epithelium is the likely source for increased VEGF.

Animals↗
PubMed2006

FTIR-microspectroscopy of prion-infected nervous tissue.

The family of transmissible spongiform encephalopathies (TSE), also termed prion diseases, is a group of fatal, neurodegenerative diseases characterized by the accumulation of a misfolded protein, the disease-associated prion protein PrPSc. This glycoprotein differs in secondary structure from its normal, cellular isoform PrPC, which is physiologically expressed mostly by neurons. Scrapie is a prion disease first described in the 18th century in sheep and goats, and has been established as a model in rodents to study the pathogenesis and pathology of prion diseases. Assuming a multitude of molecular parameters change in the tissue in the course of the disease, FTIR microspectroscopy has been proposed as a valuable new method to study and identify prion-affected tissues due to its ability to detect a variety of changes in molecular structure and composition simultaneously. This paper reviews and discusses results from previous FTIR microspectroscopic studies on nervous tissue of scrapie-infected hamsters in the context of histological and molecular alterations known from conventional pathogenesis studies. In particular, data from studies reporting on disease-specific changes of protein structure characteristics, and also results of a recent study on hamster dorsal root ganglia (DRG) are discussed. These data include an illustration on how the application of a brilliant IR synchrotron light source enables the in situ investigation of localized changes in protein structure and composition in nervous cells or tissue due to PrPSc deposition, and a demonstration on how the IR spectral information can be correlated with results of complementary studies using immunohistochemistry and x-ray fluorescence techniques. Using IR microspectroscopy, some neurons exhibited a high accumulation of disease-associated prion protein evidenced by an increased amount of beta-sheet at narrow regions in or around the infected nervous cells. However, not all neurons from terminally diseased hamsters showed PrPSc deposition. Generally, the average spectral differences between all control and diseased DRG spectra are small but consistent as demonstrated by independent experiments. Along with studies on the purified misfolded prion protein, these data suggest that synchrotron FTIR microspectroscopy is capable of detecting the misfolded prion protein in situ without the necessity of immunostaining or purification procedures.

Animals↗
PubMed2006

Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes.

The pathological hallmarks of Alzheimer's disease (AD) consist of beta-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of beta-amyloid precursor protein (AbetaPP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.

Alzheimer Disease↗
PubMed2006

Religious identity among Christian Korean-American adolescents.

This exploratory study examined religious identity among Christian Korean-American adolescents. Marcia's 1966 model of identity formation, which conceptualizes identity along dimensions of exploration and commitment, provided the framework for the current study. 49 participants, between the ages of 14 and 19 years, completed the Duke Religion Index, the religion items from the Extended Objective Measure of Ego Identity Status, the Pan-denominational Measure of Personal Devotion and Personal Conservatism, and six questions assessing perceived parental involvement. Analysis indicated that high scores on Organizational and Intrinsic Religiosity were positively correlated with the commitment statuses of Achievement and Foreclosure and negatively correlated with the noncommitment statuses of Moratorium and Diffusion. Also high scores on perceived parental involvement were positively correlated with the nonexploration status of Foreclosure and negatively correlated with the exploration status of Moratorium. Overall, the study provided a general portrait and initial examination of the formation of religious identity in a sample of Christian Korean-American adolescents.

Adolescent↗
PubMed2006

The role of immunostimulation in the development of postweaning multisystemic wasting syndrome in pigs under field conditions.

We evaluated the effects of immunostimulation in the development of postweaning multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a grower/finisher barn with a history of PMWS. The pigs were allocated to 5 treatment groups: 4 groups received a single intramuscular injection of RespiSure-ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil-based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n = 172), or physiologic saline (n = 218); 1 group received no treatment (n = 171). Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus type 2 (PCV-2) was detected by immunohistochemical testing within lesions of mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There was no significant difference in the incidence of PMWS among the groups. The findings indicate that immunostimulation did not influence the expression of PMWS in this study. Thus, routine vaccination against swine diseases may not significantly contribute to the occurrence of PMWS under field conditions.

Adjuvants, Immunologic↗
PubMed2005

Maternal depression and the intergenerational transmission of religion.

This study tests the hypothesis that maternal depression (major depressive disorder; MDD) decreases rates of the intergenerational transmission of religiosity from mother to offspring and attenuates the beneficial qualities of religiosity in offspring. Depression was assessed using semistructured clinical interviews; religiosity was assessed based upon the personal importance of religion, frequency of attendance at religious services, and religious denomination. Results suggest that (1) maternal depression attenuates the intergenerational transmission of religion; (2) in the presence of maternal depression, offspring were more likely to have MDD at 10-year follow-up when mother-offspring were concordant on religious importance; and (3) in the absence of maternal depression, offspring were less likely to have MDD at 10-year follow-up when mother-offspring were concordant on attendance. Thus, in the presence of maternal depression, transmission of religious attendance is no longer associated with decreased likelihood of offspring MDD, whereas transmission of religious importance is associated with increased likelihood of offspring depression.

Adult↗
PubMed2004

Smooth muscle development during postnatal growth of distal bronchioles in infant rhesus monkeys.

Development of smooth muscle in conducting airways begins early in fetal life. Whereas the pattern and regulation of smooth muscle differentiation are well-defined, the impact of airway growth on the process is not. To evaluate the transformations in organization during postnatal growth, smooth muscle bundle organization (size, abundance, and orientation) was mapped in five generations of distal airways of infant rhesus monkeys (5 days and 1, 2, 3, and 6 mo old). On the basis of direct measurement of the bronchiole proximal to the terminal bronchiole, length increased by 2-fold, diameter by 1.35-fold, and surface area by 2.8-fold between 5 days and 6 mo of age. Smooth muscle bundle size was greater in proximal bronchioles than in respiratory bronchioles and did not change with age. However, relative bundle size decreased in proportion to airway size as the airways grew. Relative bundle abundance was constant regardless of airway generation or age. The distribution of smooth muscle bundle orientation changed with age in each airway generation, and there were significant changes in the terminal and respiratory bronchioles. We conclude that smooth muscle undergoes marked organizational changes as airways grow during postnatal development.

Age Factors↗
PubMed2004

Site-specific metabolism of naphthalene and 1-nitronaphthalene in dissected airways of rhesus macaques.

Studies in rodents have demonstrated the importance of cytochrome P450 monooxygenases in generating reactive metabolites that produce Clara cell injury. Pulmonary P450 activities in rodents are much higher than those in primates, raising the issue of relevance of rodent data to primates. Few studies on P450-catalyzed activation of cytotoxicants in subcompartments of primate lung have been reported. Accordingly, infant monkey airway subcompartments, including trachea, proximal, midlevel, distal airways, and parenchyma, were incubated with naphthalene or 1-nitronaphthalene to define metabolism at both high (500 microM) and low (50 microM) substrate concentrations. There was a relatively even distribution of metabolizing activities for naphthalene across subcompartments, but at high concentrations of 1-nitronaphthalene, lower airways (midlevel airway through parenchyma) showed higher bioactivation than upper airways. Dihydrodiol was the predominant water-soluble metabolite of naphthalene generated by all subcompartments, whereas covalently bound metabolites accounted for the greatest percentage of 1-nitronaphthalene metabolites, especially in lower airways. As anticipated, the amounts of metabolite covalently bound as a percentage of total metabolite formed increased dramatically with the 10-fold increase in substrate concentration. With both substrates, the formation of water-soluble metabolites was approximately 100 times less than observed previously in rodents. We conclude that 1) there are significant quantitative differences between rhesus and rodents in substrate bioactivation; 2) the distribution of metabolizing activities for naphthalene but not 1-nitronaphthalene is significantly different for rodents and primates; and 3) a very high percentage of the metabolites generated, particularly for 1-nitronaphthalene, is bound covalently to cellular proteins.

Animals↗
PubMed2003

Chemical heterogeneity in cell death: combined synchrotron IR and fluorescence microscopy studies of single apoptotic and necrotic cells.

The combination of synchrotron IR microspectroscopy and fluorescence microscopy has led to the identification of specific IR signatures of apoptosis and necrosis at a single cell level. Apoptosis was induced by treatment of Fas+ tumor cell lines with anti-Fas monoclonal antibodies. Detection of the early and late stages of apoptosis was performed using conjugated annexin V-fluorescein isothiocyanate (AV-FITC) and propidium iodide. Very early cellular changes were detected by IR before externalization of phosphatidylserine and AV-FITC labeling, and they were probably linked to DNA unwinding. The IR signals at 1044, 1177, and 1222 cm(-1), as well as an intensity variation in the CHx stretching region, are the main signature changes of early and late apoptosis, in line with the hypothesis of DNA fragmentation. The increased intensity of the CHx stretching bands of the lipids was observed only at an early stage of apoptosis. Changes in the relative intensity of CH3 and CH2 stretching accompany this increased intensity, suggesting changes in the relative amount and/or type of lipids concomitant with an increased lipid content. Finally, necrotic cells were characterized by marked changes in their chemical composition because several new vibrational features were observed.

Animals↗
PubMed2003

Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue.

Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.

Animals↗
PubMed2003

Tissue mineralization is increased following 1-year treatment with high doses of bisphosphonates in dogs.

Suppression of bone turnover using anti-resorptive agents such as bisphosphonates prevents bone loss but also may increase tissue mineralization. This may make the bone more prone to initiate microcracks. The objective of this study was to determine whether suppression of remodeling caused by treatment of dogs for 1 year with five times the clinical dose of either alendronate or risedronate is associated with increased tissue mineralization and whether it changes the nature of the mineral crystal. Thirty-five dogs were divided into three weight-matched groups and treated daily for 1 year with a subcutaneous injection of saline (CON, n = 12), oral risedronate (RIS, 0.5 mg/kg/day, n = 11), or oral alendronate (ALN, 1.0 mg/kg/day, n = 12). Density fractionation, peripheral quantitative computerized tomography (pQCT), and quantitative backscattered electron microscopy (qBSE) were used to evaluate changes in mineral content of bone tissue from the vertebrae or ribs. Infrared microspectroscopy (IR) and X-ray diffraction were used to assess the quality of the mineral and some aspects of collagen structure in the thoracic vertebrae and iliac crest. Following 12 months of treatment, there was a significant shift toward higher density bone in both ALN (P = 0.04) and RIS (P = 0.002) by density fractionation methods. IR, pQCT, and qBSE did not detect any significant differences in mineralization, probably because of their lower sensitivity and/or because of the smaller region of interest they sample. No significant differences were found in the maturity of the mineral crystals or in their length or size. We conclude that treatment for 1 year with high doses of bisphosphonates which suppress bone remodeling up to 90% increases tissue mineralization, but does not change the nature of the mineral crystal.

Alendronate↗
PubMed2002

Interpersonal psychotherapy delivered over the telephone to recurrent depressives. A pilot study.

Rates of recurrent depression peak among women in their childbearing years, yet a large number of these women are not treated or do not seek maintenance treatment between episodes. Barriers to treatment include time constraints, demands of child care, and finances. A method for improving access to treatment of depression may be delivery of psychotherapy over the telephone. A 12-week pilot controlled clinical trial with random assignment was conducted to test the feasibility and efficacy of Interpersonal Psychotherapy delivered over the telephone (IPT-T) for depression in women (N=15 IPT-T and N=15 no treatment) with a life-time history of recurrent depression and low rates of previous treatment. Patients were interviewed at baseline and at 12 weeks by a blind and independent clinical evaluator to assess their symptom level and social functioning. IPT-T as compared to no treatment was significantly better in lowering symptoms of depression as measured by the Hamilton Rating Scale for Depression (p<.02), improving global functioning (GAS) (p<.02), and improving work and social functioning (p<.03-.05, respectively). These preliminary findings support the feasibility and helpfulness of IPT-T in preventing an increase in depressive symptoms among women with recurrent depression but current mild to moderately levels of depression.

Adult↗
PubMed2002

Knowledge, use, and education regarding folic acid supplementation: continuation study of women in Colorado who had a pregnancy affected by a neural tube defect.

BACKGROUND: This study was conducted to: (1) determine whether women who have had a neural tube defect (NTD) affected pregnancy know about recommendations for NTD recurrence prevention; (2) educate them about the recommendations; and (3) ensure that they have access to folic acid prior to another pregnancy. METHODS: Colorado women who had an NTD affected pregnancy in 1999 or later were interviewed about their knowledge and use of folic acid, provided with verbal information about folic acid and NTD prevention, and offered written information and a voucher for free folic acid. RESULTS: Thirty-two of 68 women who had an NTD affected pregnancy were interviewed. Of these, 22 (69%) were aware of the 0.4 mg. folic acid recommendation for women of child bearing age who have not had an NTD affected pregnancy (MMWR, '91). Only 15 (47%) of the women knew about the U.S. Public Health Service recommendation (MMWR, '92) to consume 4.0 mg of folic acid prior to another pregnancy for NTD recurrence prevention. Twenty-five (78%) of the women reported taking a multivitamin or folic acid daily. CONCLUSIONS: Nine years after national folic acid recommendations, a majority of interviewed women (53%) with NTD affected pregnancies did not know about the recommendation to consume 4.0 mg of folic acid for NTD recurrence prevention. This sample of women are receptive to information about folic acid. Health care providers and public health officials should ensure that education about folic acid is provided in an effective and timely manner to women with NTD-affected pregnancies.

Colorado↗