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Biomedical subjects

T M Miller

Publications and source records attributed to T M Miller.

At least 19 recordsLinked to original sources
PubMed2005

HETC radiation transport code development for cosmic ray shielding applications in space.

In order to facilitate three-dimensional analyses of space radiation shielding scenarios for future space missions, the Monte Carlo radiation transport code HETC is being extended to include transport of energetic heavy ions, such as are found in the galactic cosmic ray spectrum in space. Recently, an event generator capable of providing nuclear interaction data for use in HETC was developed and incorporated into the code. The event generator predicts the interaction product yields and production angles and energies using nuclear models and Monte Carlo techniques. Testing and validation of the extended transport code has begun. In this work, the current status of code modifications, which enable energetic heavy ions and their nuclear reaction products to be transported through thick shielding, are described. Also, initial results of code testing against available laboratory beam data for energetic heavy ions interacting in thick targets are presented.

Construction Materials↗
PubMed2004

Correlating phenotype and genotype in the periodic paralyses.

BACKGROUND: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease. OBJECTIVE: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease. METHODS: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis (47 kindreds, 99 patients), and paramyotonia congenita (24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations. RESULTS: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide. CONCLUSIONS: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients (127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy.

Adolescent↗
PubMed2004

First observation of four-body breakup in electron recombination: C2D+5.

We report the first observation of four-body breakup in electron dissociative recombination of a molecular ion: C2D+5. In an ion storage ring experiment, the branching ratio for the process C2D+5 + e(-)-->C2D2 + D + D + D was determined to be 13%. This means that three covalent chemical bonds are broken as a result of the action of a single electron. This is the first time a four-body breakup of chemical bonds has been observed in a low-energy binary reaction.

Journal Article↗
PubMed2004

Double-differential light-ion production cross sections.

Codes used for space radiation shielding studies typically transport light-ions from the incident cosmic ray spectrum using either a one-dimensional straight-ahead approximation or in three dimensions, often without accounting for their breakup. Light-ions are also produced by breakup of energetic heavy ions in target materials. Herein, we present cross section models that can be used to predict double-differential light-ion production cross sections. Deuteron breakup is based on a parameterization of the total reaction cross sections. Alpha fragmentation utilizes a parameterization based on an abrasion-ablation model that has been augmented by experimental data. Neutron and proton production is modelled with a quantum mechanical abrasion-ablation-coalescence model. This same model is also used to predict cross sections for triton and 3He breakup. Finally, energies and emission angles for particles other than nucleons are specified using a model of energy degradation in nucleus-nucleus collisions and systematics of momentum distributions.

Algorithms↗
PubMed2004

Double-differential heavy-ion production cross sections.

Current computational tools used for space or accelerator shielding studies transport energetic heavy ions either using a one-dimensional straight-ahead approximation or by dissociating the nuclei into protons and neutrons and then performing neutron and proton transport using Monte Carlo techniques. Although the heavy secondary particles generally travel close to the beam direction, a proper treatment of the light ions produced in these reactions requires that double-differential cross sections should be utilised. Unfortunately, no fundamental nuclear model capable of serving as an event generator to provide these cross sections for all ions and energies of interest exists currently. Herein, we present a model for producing double-differential heavy-ion production cross sections that uses heavy-ion fragmentation yields produced by the NUCFRG2 fragmentation code coupled with a model of energy degradation in nucleus-nucleus collisions and systematics of momentum distributions to provide energy and angular dependences of the heavy-ion production.

Algorithms↗
PubMed2003

Particle formation by ion nucleation in the upper troposphere and lower stratosphere.

Unexpectedly high concentrations of ultrafine particles were observed over a wide range of latitudes in the upper troposphere and lower stratosphere. Particle number concentrations and size distributions simulated by a numerical model of ion-induced nucleation, constrained by measured thermodynamic data and observed atmospheric key species, were consistent with the observations. These findings indicate that, at typical upper troposphere and lower stratosphere conditions, particles are formed by this nucleation process and grow to measurable sizes with sufficient sun exposure and low preexisting aerosol surface area. Ion-induced nucleation is thus a globally important source of aerosol particles, potentially affecting cloud formation and radiative transfer.

Journal Article↗
PubMed2000

Effectiveness of Agency for Health Care Policy and Research clinical practice guideline and patient education methods for pregnant smokers in medicaid maternity care.

OBJECTIVE: The purposes of this study were (1) to determine the extent to which tobacco exposure assessment and new patient education methods, derived from a meta-analysis and the Agency for Health Care Policy and Research guideline recommendations, could be provided routinely by trained Medicaid maternity care staff members and (2) to document the behavioral impact of these interventions among pregnant smokers. STUDY DESIGN: After 265 pregnant smokers were assigned at their first visit to an experimental group (n = 139) or a control group (n = 126), they received standardized risk information and were advised to quit smoking. The experimental group also received evidence-based patient education methods, including the videocassette Commit to Quit During and After Pregnancy, the publication A Pregnant Woman's Guide to Quit Smoking, and a brief counseling session. Self-report and saliva cotinine assessments of tobacco exposure were performed at baseline and at the end of pregnancy. RESULTS: A significantly higher percentage of patients quit smoking in the experimental group (17.3%) than in the control group (8.8%). CONCLUSIONS: The application of principles of organizational development and quality improvement at the management and clinical practice levels and the delivery of evidence-based health education methods by trained prenatal care providers significantly increased smoking cessation rates among pregnant Medicaid recipients.

Cotinine↗
PubMed1999

Enhancement of clinicians' diagnostic reasoning by computer-based consultation: a multisite study of 2 systems.

CONTEXT: Computer-based diagnostic decision support systems (DSSs) were developed to improve health care quality by providing accurate, useful, and timely diagnostic information to clinicians. However, most studies have emphasized the accuracy of the computer system alone, without placing clinicians in the role of direct users. OBJECTIVE: To explore the extent to which consultations with DSSs improve clinicians' diagnostic hypotheses in a set of diagnostically challenging cases. DESIGN: Partially randomized controlled trial conducted in a laboratory setting, using a prospective balanced experimental design in 1995-1998. SETTING: Three academic medical centers, none of which were involved in the development of the DSSs. PARTICIPANTS: A total of 216 physicians: 72 at each site, including 24 internal medicine faculty members, 24 senior residents, and 24 fourth-year medical students. One physician's data were lost to analysis. INTERVENTION: Two DSSs, ILIAD (version 4.2) and Quick Medical Reference (QMR; version 3.7.1), were used by participants for diagnostic evaluation of a total of 36 cases based on actual patients. After training, each subject evaluated 9 of the 36 cases, first without and then using a DSS, and suggested an ordered list of diagnostic hypotheses after each evaluation. MAIN OUTCOME MEASURE: Diagnostic accuracy, measured as the presence of the correct diagnosis on the hypothesis list and also using a derived diagnostic quality score, before and after consultation with the DSSs. RESULTS: Correct diagnoses appeared in subjects' hypothesis lists for 39.5% of cases prior to consultation and 45.4% of cases after consultation. Subjects' mean diagnostic quality scores increased from 5.7 (95% confidence interval [CI], 5.5-5.9) to 6.1 (95% CI, 5.9-6.3) (effect size: Cohen d = 0.32; 95% CI, 0.23-0.41; P<.001). Larger increases (P = .048) were observed for students than for residents and faculty. Effect size varied significantly (P<.02) by DSS (Cohen d = 0.20; 95% CI, 0.08-0.32 for ILIAD vs Cohen d = 0.45; 95% CI, 0.31-0.59 for QMR). CONCLUSIONS: Our study supports the idea that "hands-on" use of diagnostic DSSs can influence diagnostic reasoning of clinicians. The larger effect for students suggests a possible educational role for these systems.

Decision Support Techniques↗
PubMed1998

The effect of professional education on the knowledge and attitudes of physical therapist and occupational therapist students about acquired immunodeficiency syndrome.

BACKGROUND AND PURPOSE: Anxiety and fear about caring for people with acquired immunodeficiency syndrome (AIDS) are concerns expressed by students in health care professions. This study was designed to evaluate the influence of education offered to physical therapist (PT) and occupational therapist (OT) students on their knowledge, attitudes, and willingness to provide services to people with AIDS. SUBJECTS AND METHODS: Twenty-six undergraduate PT students and 23 undergraduate OT students completed a questionnaire at the beginning of their professional education program, following a 5-hour AIDS education seminar, and shortly before their graduation. The questionnaire consisted of 3 subscales designed to evaluate the respondents' knowledge, attitudes, and willingness to treat people with AIDS. RESULTS: At the time of graduation, the students in both disciplines showed improvement in knowledge about AIDS (14.3% for PT students and 13.8% for OT students) and more positive attitudes toward people with AIDS (7.4% for PT students and 5% for OT students). In both disciplines, the students' willingness to provide services for people with AIDS remained unchanged following the AIDS education seminar and at the end of the professional education program. CONCLUSION AND DISCUSSION: The professional education offered to the cohort of students in this study appeared to be beneficial in improving their knowledge and attitudes toward people with AIDS, but it did not affect their willingness to work with this patient group.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death.

Dissociated cerebellar granule cells maintained in medium containing 25 mM potassium undergo an apoptotic death when switched to medium with 5 mM potassium. Granule cells from mice in which Bax, a proapoptotic Bcl-2 family member, had been deleted, did not undergo apoptosis in 5 mM potassium, yet did undergo an excitotoxic cell death in response to stimulation with 30 or 100 microM NMDA. Within 2 h after switching to 5 mM K+, both wild-type and Bax-deficient granule cells decreased glucose uptake to <20% of control. Protein synthesis also decreased rapidly in both wild-type and Bax-deficient granule cells to 50% of control within 12 h after switching to 5 mM potassium. Both wild-type and Bax -/- neurons increased mRNA levels of c-jun, and caspase 3 (CPP32) and increased phosphorylation of the transactivation domain of c-Jun after K+ deprivation. Wild-type granule cells in 5 mM K+ increased cleavage of DEVD-aminomethylcoumarin (DEVD-AMC), a fluorogenic substrate for caspases 2, 3, and 7; in contrast, Bax-deficient granule cells did not cleave DEVD-AMC. These results place BAX downstream of metabolic changes, changes in mRNA levels, and increased phosphorylation of c-Jun, yet upstream of the activation of caspases and indicate that BAX is required for apoptotic, but not excitotoxic, cell death. In wild-type cells, Boc-Asp-FMK and ZVAD-FMK, general inhibitors of caspases, blocked cleavage of DEVD-AMC and blocked the increase in TdT-mediated dUTP nick end labeling (TUNEL) positivity. However, these inhibitors had only a marginal effect on preventing cell death, suggesting a caspase-independent death pathway downstream of BAX in cerebellar granule cells.

Animals↗
PubMed1997

Inhibition of phosphatidylinositol 3-kinase activity blocks depolarization- and insulin-like growth factor I-mediated survival of cerebellar granule cells.

Depolarizing concentrations of potassium promote the survival of many neuronal cell types including cerebellar granule cells. To begin to understand the intracellular mediators of neuronal survival, we have tested whether the survival-promoting effect of potassium depolarization on cerebellar granule cells is dependent on either mitogen-activated protein (MAP) kinase or phosphatidylinositol 3-kinase (PI-3-K) activity. In 7-day cerebellar granule cell cultures, potassium depolarization activated both MAP kinase and PI-3-K. Preventing the activation of MAP kinase with the MEK1 inhibitor PD98059 did not affect potassium saving. In contrast, the survival-promoting effect of 25 mM potassium was negated by the addition of 30 microM LY 294002 or 1 microM wortmannin, two distinct inhibitors of PI-3-K. The cell death induced by PI-3-K inhibition was indistinguishable from the cell death caused by potassium deprivation; LY 294002-induced death included nuclear condensation, was blocked by cycloheximide, and had the same time course as potassium deprivation-induced cell death. Cerebellar granule cells can also be maintained in serum-free medium containing either 100 ng/ml insulin-like growth factor I (IGF-I) or 800 microM cAMP. PI-3-K inhibition completely blocked the survival-promoting activity of IGF-I, but had no effect on cAMP-mediated survival. These data indicate that the survival-promoting effects of depolarization and IGF-I, but not cAMP, require PI-3-K activity.

Androstadienes↗
PubMed1996

Metabolic and genetic analyses of apoptosis in potassium/serum-deprived rat cerebellar granule cells.

Cerebellar granule cells maintained in medium containing serum and 25 mM potassium undergo an apoptotic death within 96 hr when switched to serum-free medium with 5 mM potassium. Because large numbers of apparently homogeneous neurons can be obtained, this represents a potentially useful model of neuronal programmed cell death (PCD). Analysis of the time course and extent of death after removal of either serum or K+ alone demonstrated that a fast-dying (T(1/2) = 4 hr) population (20%) responded to serum deprivation, whereas a slow-dying (T(1/2) = 25 hr) population (80%) died in response to K+ deprivation. Taking advantage of the complete death after removing both K+ and serum, changes in metabolic events and mRNA levels were analyzed in this model. Glucose uptake, protein synthesis, and RNA synthesis fell to <35% of control by 9 hr after potassium/serum deprivation, a time when 85% of the cells were still viable. The pattern of the fall in these metabolic parameters was similar to that reported for trophic factor-deprived sympathetic neurons. Most mRNAs decreased markedly after K+/serum deprivation. Levels of c-jun mRNA increased fivefold in potassium/serum-deprived granule cells; c-jun is required for cell death of sympathetic neurons. mRNA levels of cyclin D1, c-myb, collagenase, and transin remained relatively constant in potassium/serum-deprived granule cells. These data demonstrate the existence of two populations of granule cells with respect to cell death and define common metabolic and genetic events involved in neuronal PCD.

Animals↗
PubMed1993

Maturational asynchrony between oocyte cumulus-coronal morphology and nuclear maturity in gonadotropin-releasing hormone agonist stimulations.

OBJECTIVE: To determine oocyte meiotic maturity and asynchrony between cumulus-coronal morphology and nuclear maturity after gonadotropin-releasing hormone agonist (GnRH-a) and norethindrone-programmed stimulations. DESIGN: Oocyte meiotic maturity was evaluated at follicular aspiration in 4,961 oocytes after GnRH-a/follicle-stimulating hormone (FSH)/human menopausal gonadotropin stimulations (hMG) for in vitro fertilization patients and 299 oocytes after norethindrone-programmed clomiphene citrate (CC)/hMG in oocyte donors. Maturational asynchrony between the oocyte's cumulus-coronal morphology and nuclear maturity was evaluated in 2,336 oocytes. SETTING: In vitro fertilization program at the University of Iowa Hospitals and Clinics; academic tertiary care center. INTERVENTIONS: After evaluating oocyte cumulus-coronal maturity, cumulus masses were spread to determine oocyte nuclear maturity. RESULTS: Fourteen percent, 17%, 50%, 17%, and 2% of oocytes were prophase I, metaphase I, metaphase II, postmature metaphase II, and atretic, respectively. Asynchrony was noted in 28% of prophase I, 71% of metaphase I, 11% of metaphase II, 45% of postmature metaphase II, 32% of atretic, and 28% of all oocytes. Significant differences were not found between GnRH-a and norethindrone-programmed stimulations in asynchrony between cumulus-coronal morphology and nuclear maturity or percentage of prophase I, metaphase I, metaphase II, postmature metaphase II, or atretic oocytes. Sixty-seven percent of oocytes possessed a polar body at retrieval. The rate of fertilization was significantly higher for metaphase II oocytes than postmature metaphase II and metaphase I oocytes > prophase I oocytes. Parthenogenetic activation tended to be highest for postmature metaphase II oocytes. Embryo cleavage was significantly higher for postmature metaphase II, metaphase II, and metaphase I oocytes than for prophase I oocytes. CONCLUSIONS: This is the first report of asynchrony between cumulus-coronal morphology and nuclear maturity at follicular aspiration in GnRH-a and norethindrone-programmed stimulations. Asynchrony was observed in 28% of oocytes. A higher percentage of oocytes possessed a polar body at egg retrieval with these stimulation regimens compared with rates reported previously for FSH, FSH/hMG, and CC/hMG stimulations.

Cell Cycle↗
PubMed1992

Prediction of nuclear maturity from cumulus-coronal morphology: influence of embryologist experience.

PURPOSE: A majority of in vitro fertilization (IVF) programs continues to evaluate oocyte maturity on the basis of cumulus-coronal morphology (CCM) even though marked asynchrony has been reported between CCM and nuclear maturity. This study was designed to examine changes in embryologists' ability to correctly predict nuclear maturity from CCM as a function of increasing experience. Nuclear maturity was assessed by inverted microscopy with a modified spreading technique at follicular aspiration. A second objective was to determine the percentage of oocytes which displayed asynchrony between CCM and nuclear maturity as assessed by embryologists with extensive experience in oocyte maturity evaluation. RESULTS: The three participating embryologists had directly evaluated 1304, 75, and 0 oocytes for nuclear maturity and CCM at study initiation and correctly predicted nuclear maturity from CCM in 74, 64, and 47% of oocytes, respectively. Embryologist 1 did not significantly change in predictive ability during the 17-month study period. Embryologist 2 significantly improved in predictive ability during the first 9 months of the study (841 oocytes evaluated) and plateaued thereafter, at a similar percentage of correct predictions as embryologist 1. Embryologist 3 continued to improve in predictive ability throughout the study period, reaching 61% correct predictions at the close of the study after evaluating 223 oocytes. Once embryologists had plateaued in their predictive ability, 72% of oocytes evaluated received the correct nuclear maturity classification based on CCM. Significantly fewer oocytes (54%; 375/690) evaluated by embryologists who had not plateaued in their predictive ability received the correct nuclear maturity classification based on CCM. CONCLUSIONS: These results indicate that embryologists' ability to predict oocyte nuclear maturity correctly from CCM continues to change over several months even when pretraining video recordings are used before beginning direct evaluations. After embryologists plateaued in their predictive ability, nuclear maturity still could not be correctly predicted from CCM in 28% of oocytes due to asynchrony between nuclear and CCM maturity. Based upon this, circumstances in which the spreading technique should be used for direct assessment of nuclear maturity as opposed to assessment of CCM only are discussed.

Cell Differentiation↗
PubMed1992

Identification and characterization of an actin-binding site of CapZ.

A mAb (1E5) that binds the COOH-terminal region of the beta subunit of chicken CapZ inhibits the ability of CapZ to bind the barbed ends of actin filaments and nucleate actin polymerization. CapZ prepared as fusion proteins in bacteria or nonfusion proteins by in vitro translation has activity similar to that of CapZ purified from muscle. Deletion of the COOH-terminus of the beta subunit of CapZ leads to a loss of CapZ's ability to bind the barbed ends of actin filaments. A peptide corresponding to the COOH-terminal region of CapZ beta, expressed as a fusion protein, binds actin monomers. The mAb 1E5 also inhibits the binding of this peptide to actin. These results suggest that the COOH-terminal region of the beta subunit of CapZ is an actin-binding site. The primary structure of this region is not similar to that of potential actin-binding sites identified in other proteins. In addition, the primary structure of this region is not conserved across species.

Actin Cytoskeleton↗
PubMed1991

Treatment of severe male-factor infertility with high concentrations of motile sperm by microinsemination in embryo cryopreservation straws.

A microinsemination technique was evaluated for treating our program's most severe cases of male-factor infertility. Oocytes were inseminated with high concentrations of motile sperm (1 to 9 x 10(6)/ml) in 10 to 150 microliters within embryo cryopreservation straws. Fertilization was obtained in 20 of 29 (69%) couples treated by this technique. In the 15 patients in which only embryos generated from the straw technique were transferred, 7 clinical pregnancies resulted (46.7% per transfer). The implantation rate for couples receiving embryos from the straw technique only (12/58; 20.7%) compared favorably to that observed for other cases treated during this same time period with regular insemination techniques (111/766; 14.5%). Clinical pregnancy rates per transfer for IVF-ET, TET, and PROST were 33.0% (1/3), 0% (0/2), and 60.0% (6/10), respectively. The percentage of polyploidic embryos was significantly lower (P less than 0.0001) for male-factor patients treated by the straw technique with high sperm concentrations than for non-male-factor patients treated during this same time period with standard sperm concentrations. Normal births have resulted from straw inseminations with 3.4 x 10(6) and ongoing pregnancies with 5.0 x 10(6) motile sperm/ml. The results of this study suggest that some cases of male-factor infertility can be successfully treated by insemination with high concentrations of motile sperm in embryo cryopreservation straws. A technique of centrifuging sperm in straws was also developed to concentrate the entire fraction of washed sperm into 10 microliters. Further development of this technique may allow treatment of more severe cases of oligo/asthenospermia by microinsemination with high concentrations of motile sperm than is presently possible with standard washing techniques.

Adult↗