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Biomedical subjects

Michael Miller

Publications and source records attributed to Michael Miller.

89 records · Page 5Linked to original sources
PubMed2002

Design and implementation of microarray gene expression markup language (MAGE-ML).

BACKGROUND: Meaningful exchange of microarray data is currently difficult because it is rare that published data provide sufficient information depth or are even in the same format from one publication to another. Only when data can be easily exchanged will the entire biological community be able to derive the full benefit from such microarray studies. RESULTS: To this end we have developed three key ingredients towards standardizing the storage and exchange of microarray data. First, we have created a minimal information for the annotation of a microarray experiment (MIAME)-compliant conceptualization of microarray experiments modeled using the unified modeling language (UML) named MAGE-OM (microarray gene expression object model). Second, we have translated MAGE-OM into an XML-based data format, MAGE-ML, to facilitate the exchange of data. Third, some of us are now using MAGE (or its progenitors) in data production settings. Finally, we have developed a freely available software tool kit (MAGE-STK) that eases the integration of MAGE-ML into end users' systems. CONCLUSIONS: MAGE will help microarray data producers and users to exchange information by providing a common platform for data exchange, and MAGE-STK will make the adoption of MAGE easier.

Computer Simulation↗
PubMed2002

Novel ABCA1 compound variant associated with HDL cholesterol deficiency.

The recent discovery of an ATP-binding cassette transporter, ABCA1, as an important regulator of high density lipoprotein (HDL) metabolism and reverse cholesterol transport has facilitated the identification of novel variants associated with HDL cholesterol deficiency states. We identified a subject with HDL cholesterol deficiency (4 mg/dl) who developed and died of complications related to cerebral amyloid angiopathy (CAA). The proband had a compound heterozygous mutation. One mutation was a G3295T substitution with conversion of asparagine to tyrosine (D1099Y) in ABCA1. The single-base substitution at codon 1099 resulted in the abolition of an RsaI cleavage site. The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). The presence of the T5966C mutation was detected by restriction digestion with HinfI. These variants were not identified in over 400 chromosomes of healthy subjects. In the kindred, family members heterozygous for the ABCA1 variant exhibited low levels of HDL cholesterol. Direct sequencing of all coding regions and splice site junctions of other HDL candidate genes revealed no additional mutations, indicating that combined defective ABCA1 alleles may result in familial HDL deficiency.

ATP Binding Cassette Transporter 1↗
PubMed2002

Cognitive functioning of long-term heavy cannabis users seeking treatment.

CONTEXT: Cognitive impairments are associated with long-term cannabis use, but the parameters of use that contribute to impairments and the nature and endurance of cognitive dysfunction remain uncertain. OBJECTIVE: To examine the effects of duration of cannabis use on specific areas of cognitive functioning among users seeking treatment for cannabis dependence. DESIGN, SETTING, AND PARTICIPANTS: Multisite retrospective cross-sectional neuropsychological study conducted in the United States (Seattle, Wash; Farmington, Conn; and Miami, Fla) between 1997 and 2000 among 102 near-daily cannabis users (51 long-term users: mean, 23.9 years of use; 51 shorter-term users: mean, 10.2 years of use) compared with 33 nonuser controls. MAIN OUTCOME MEASURES: Measures from 9 standard neuropsychological tests that assessed attention, memory, and executive functioning, and were administered prior to entry to a treatment program and following a median 17-hour abstinence. RESULTS: Long-term cannabis users performed significantly less well than shorter-term users and controls on tests of memory and attention. On the Rey Auditory Verbal Learning Test, long-term users recalled significantly fewer words than either shorter-term users (P =.001) or controls (P =.005); there was no difference between shorter-term users and controls. Long-term users showed impaired learning (P =.007), retention (P =.003), and retrieval (P =.002) compared with controls. Both user groups performed poorly on a time estimation task (P<.001 vs controls). Performance measures often correlated significantly with the duration of cannabis use, being worse with increasing years of use, but were unrelated to withdrawal symptoms and persisted after controlling for recent cannabis use and other drug use. CONCLUSIONS: These results confirm that long-term heavy cannabis users show impairments in memory and attention that endure beyond the period of intoxication and worsen with increasing years of regular cannabis use.

Adult↗
PubMed2002

Update on the role of triglycerides as a risk factor for coronary heart disease.

Elevated triglyceride levels represent an independent risk factor for coronary heart disease, and recently the National Cholesterol Education Program revised the acceptable level of fasting triglycerides from less than 200 mg/dL to below 150 mg/dL. However, a sizeable proportion of people in Western societies has persistently elevated triglyceride levels. Fortunately, hygienic and pharmacologic measures can have a considerable impact on reducing triglyceride levels. However, an important yet unanswered question is whether decreasing triglycerides beyond low-density lipoprotein cholesterol lowering contributes significantly to additional coronary heart disease event reduction.

Coronary Disease↗
PubMed2002

ABCA1(Alabama): a novel variant associated with HDL deficiency and premature coronary artery disease.

The ATP-binding cassette transporter, ABCA1, is a member of the ABC superfamily of proteins involved in the active transport of substrates across cellular membranes. Recent studies have implicated mutations in ABCA1 as the cause of Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA). To evaluate the molecular basis of low high density lipoprotein (HDL) in a family with premature coronary artery disease, single strand conformational polymorphism analysis was performed for all coding regions and splice site junctions of ABCA1 with the genomic DNA of the proband. The proband and affected individuals were heterozygotes for C254T with proline converted to leucine (P85L). This mutation was not identified in over 400 chromosomes of healthy subjects. In the FHA kindred, family members heterozygous for the ABCA1 variant also exhibited corresponding low levels of HDL cholesterol. These data confirm recent data that a single defective allele in ABCA1 may be associated with reduced HDL cholesterol and FHA.

ATP-Binding Cassette Transporters↗
PubMed2002

High efficiency transgene segregation in co-transformed maize plants using an Agrobacterium tumefaciens 2 T-DNA binary system.

For regulatory issues and research purposes it would be desirable to have the ability to segregate transgenes in co-transformed maize. We have developed a highly efficient system to segregate transgenes in maize that was co-transformed using an Agrobacterium tumefaciens 2 T-DNA binary system. Three vector treatments were compared in this study; (1) a 2 T-DNA vector, where the selectable marker gene bar (confers resistance to bialaphos) and the beta-glucuronidase (GUS) reporter gene are on two separate T-DNA's contained on a single binary vector; (2) a mixed strain treatment, where bar and GUS are contained on single T-DNA vectors in two separate Agrobacterium strains; (3) and a single T-DNA binary vector containing both bar and GUS as control treatment. Bialaphos resistant calli were generated from 52 to 59% of inoculated immature embryos depending on treatment. A total of 93.4% of the bialaphos selected calli from the 2 T-DNA vector treatment exhibited GUS activity compared to 11.7% for the mixed strain treatment and 98.2% for the cis control vector treatment. For the 2 T-DNA vector treatment, 86.7% of the bialaphos resistant/GUS active calli produced R0 plants exhibiting both transgenic phenotypes compared to 10% for the mixed strain treatment and 99% for the single T-DNA control vector treatment. A total of 87 Liberty herbicide (contains bialaphos as the active ingredient) resistant/GUS active R0 events from the 2 T-DNA binary vector treatment were evaluated for phenotypic segregation of these traits in the R1 generation. Of these R0 events, 71.4% exhibited segregation of Liberty resistance and GUS activity in the R1 generation. A total of 64.4% of the R0 2 T-DNA vector events produced Liberty sensitive/GUS active (indicating selectable-marker-free) R1 progeny. A high frequency of phenotypic segregation was also observed using the mixed strain approach, but a low frequency of calli producing R0 plants displaying both transgenic phenotypes makes this method less efficient. Molecular analyses were then used to confirm that the observed segregation of R1 phenotypes were highly correlated to genetic segregation of the bar and GUS genes. A high efficiency system to segregate transgenes in co-transformed maize plants has now been demonstrated.

Agrobacterium tumefaciens↗
PubMed2002

Tailoring cannabis dependence treatment for a diverse population.

Accumulating evidence suggests that psychosocial treatment for cannabis dependence is effective. Earlier investigations were well designed and sought to evaluate efficacy of manual-guided therapies with particular attention to protecting the independent variable. The Marijuana Treatment Project (MTP) represents an effort to build upon previous knowledge about cannabis dependence treatment through an evaluation of an integrative therapy, which was meant to allow for greater therapist latitude in its delivery, and to be more responsive to a potentially more diverse population of clients. The treatment intervention developed for delivery in the Marijuana Treatment Project (MTP) reflects an effort to find a true compromise between the needs of the scientific community to have clearly specified and measurable treatments, and the realities of the treatment community, which demand flexibility, appreciation of the multi-determined nature of most problems, and individualized approaches. This paper will describe the clinical interventions used with the MTP participants, the theoretical rationale guiding their design and practical aspects related to implementation and treatment response.

Decision Making↗
PubMed2002

The Marijuana Treatment Project: rationale, design and participant characteristics.

AIMS: Recent findings regarding the prevalence of marijuana dependence and associated consequences indicate the need for empirically validated treatments for this population. The Marijuana Treatment Project (MTP) was a multi-site study of two treatments for adults with marijuana dependence. DESIGN: Participants (N= 450) were randomly assigned to one of three conditions at each of three sites: 1) a 9-session cognitive behavioral treatment (CBT) with motivational enhancement therapy (MET) and case management (CM) components; 2) a 2-session MET intervention; or 3) a delayed treatment control (DTC). SETTING: The study was conducted in outpatient drug treatment clinics in three U.S. cities. PARTICIPANTS: Participants were individuals aged 18 or over who met diagnostic criteria for cannabis dependence and who voluntarily presented for treatment. MEASUREMENT: Study variables included DSM-IV dependence criteria, timeline follow-back assessment of drug use, Addiction Severity Index composite scores, and problems related to marijuana use. FINDINGS: Participants were daily users, who smoked marijuana multiple times per day, and had been doing so for more than 15 years. They reported multiple dependence symptoms and negative consequences related to marijuana use. Approximately 32% of the sample was female, and 30% of the sample was either Hispanic (17%), African American (12%), or of mixed racial backgrounds (1%). CONCLUSIONS: The multi-site nature of the MTP allowed for the recruitment of a more ethnically and gender diverse sample than had been studied previously but there were few differences in the clinical characteristics of participants at the geographically and sociodemographically diverse study sites.

Adolescent↗
PubMed2002

Correlates of pre-treatment drop-out among persons with marijuana dependence.

AIMS: Our objective was to identify client characteristics and other factors associated with pre-treatment drop-out by people with marijuana dependence. DESIGN AND PARTICIPANTS: Data from the Marijuana Treatment Project's screening assessment were used to examine correlates of pre-treatment drop-out. Information from all eligible study participants (n = 813) (i.e. those who were interested in receiving treatment for their marijuana dependence and were determined to be eligible for the randomized treatment efficacy trial) was used to examine differences between the 450 participants who initiated treatment (by enrolling in the trial) and the 363 individuals who declined enrollment. SETTING: The study was conducted at three community-based outpatient treatment facilities in Farmington, CT, Seattle, WA and Miami, FL. MEASUREMENTS: The information gathered in the screening interview included demographic characteristics, residential stability variables, employment and education history and referral source. Substance use variables included the number of days and the number of times per day marijuana was used, self-perceived dependence on marijuana, alcohol or other drugs, other drug use history and current treatment (i.e. substance abuse, medical, psychiatric) situation. FINDINGS: Stepwise logistic regression was conducted to confirm variables associated with treatment initiation in bivariate analyses. Pre-treatment drop-out was associated with being younger, unmarried, unemployed, less educated and Asian American or Native American. It was also associated with self-perceived dependence on marijuana and use of other drugs. CONCLUSIONS: By recognizing demographic and substance use factors that may serve as barriers for individuals accessing treatment for marijuana dependence, clinicians may target clients with these characteristics proactively to encourage treatment initiation and subsequent attendance.

Adolescent↗
PubMed2002

Chromosomal location plays a role in regulation of aflatoxin gene expression in Aspergillus parasiticus.

The nor-1 gene in the filamentous fungus Aspergillus parasiticus encodes a ketoreductase involved in aflatoxin biosynthesis. To study environmental influences on nor-1 expression, we generated plasmid pAPGUSNNB containing a nor-1 promoter-beta-glucuronidase (GUS) (encoded by uidA) reporter fusion with niaD (encodes nitrate reductase) as a selectable marker. niaD transformants of A. parasiticus strain NR-1 (niaD) carried pAPGUSNNB integrated predominantly at the nor-1 or niaD locus. Expression of the native nor-1 and nor-1::GUS reporter was compared in transformants grown under aflatoxin-inducing conditions by Northern and Western analyses and by qualitative and quantitative GUS activity assays. The timing and level of nor-1 promoter function with pAPGUSNNB integrated at nor-1 was similar to that observed for the native nor-1 gene. In contrast, nor-1 promoter activity in pAPGUSNNB and a second nor-1::GUS reporter construct, pBNG3.0, was not detectable when integration occurred at niaD. Because niaD-dependent regulation could account for the absence of expression at niaD, a third chromosomal location was analyzed using pAPGUSNP, which contained nor-1::GUS plus pyrG (encodes OMP decarboxylase) as a selectable marker. GUS expression was detectable only when pAPGUSNP integrated at nor-1 and was not detectable at pyrG, even under growth conditions that required pyrG expression. nor-1::GUS is regulated similarly to the native nor-1 gene when it is integrated at its homologous site within the aflatoxin gene cluster but is not expressed at native nor-1 levels at two locations outside of the aflatoxin gene cluster. We conclude that the GUS reporter system can be used effectively to measure nor-1 promoter activity and that nor-1 is subject to position-dependent regulation in the A. parasiticus chromosome.

Aflatoxins↗
PubMed2002

The effect of implant constraint on results of conversion of unicompartmental knee arthroplasty to total knee arthroplasty.

A series of unicompartmental knee arthroplasty (UKA) revision to total knee arthroplasty (TKA) was compared to a group of primary TKAs performed at the same institution. The UKA revision group had a higher incidence of local wound complications and inferior clinical results as measured by Knee Society scores. When the revisions were stratified by the degree of interface constraint, knees revised with posterior cruciate ligament (PCL) substituting designs had superior knee scores that were comparable to the primary group. The use of a PCL-substituting knee design is recommended when converting a UKA to TKA.

Aged↗
PubMed2002

Lack of association between increased carotid intima-media thickening and decreased HDL-cholesterol in a family with a novel ABCA1 variant, G2265T.

Low HDL-cholesterol (HDL-C) concentrations are inversely correlated with cardiovascular disease, and previous studies have demonstrated that variants in the ATP-binding cassette transporter, ABCA1, are responsible for a proportion of HDL-C deficiency states. We identified a novel variant in ABCA1 in a kindred with decreased HDL-C. This variant was not identified in >200 chromosomes of healthy individuals. The proband, a heterozygote for G2265T, developed premature coronary artery disease. In addition to low HDL-C, six biological family members heterozygous for the ABCA1 variant exhibited low HDL-C concentrations compared with unaffected family members (0.83 +/- 0.32 vs 1.33 +/- 0.36 mmol/L; P = 0.009). Despite the decreased HDL-C, carotid artery B-mode ultrasound studies failed to reveal increased intima-media thickening in affected individuals compared with age- and sex-matched controls. Although these data extend previous observations that a single defective ABCA1 allele may lead to decreased HDL-C, associated evidence of early atherosclerosis was not confirmed.

ATP Binding Cassette Transporter 1↗
PubMed2002

Passive resistive torque of the plantar flexors following eccentric loading as assessed by isokinetic dynamometry.

Isokinetic dynamometers may provide a useful means of measuring muscle stiffness resulting from eccentric exercise because they can measure torque from computer-controlled passive movements of joints (passive resistive torque; PRT). In this study, a Biodex measured increased ankle PRT (52%; p <.001) following heel drop exercise in nine young women. Therefore, isokinetic dynamometers can provide a means to study group changes as a result of eccentric exercise. Future studies are required to determine the reliability of this protocol before it can be advocated in studying single cases.

Adult↗
PubMedDate not supplied

The policy and political context of defending Medicaid.

Medicaid is often accused of devouring state budgets. In reality, it is a sharp decline in revenue that has precipitated the current state fiscal crisis, not the growth of health care spending. Nonetheless, in a climate of scarce resources, proponents of maintaining health coverage for low-income people through the Medicaid program face a complex challenge that requires them to think simultaneously about policy and building a political constituency for health care for the poor. At the same time, they must challenge the conventional wisdom that argues against raising taxes in times of economic weakness.

Adult↗
PubMedDate not supplied

Long-term user perceptions of an implanted neuroprosthesis for exercise, standing, and transfers after spinal cord injury.

This study was completed to understand the usage patterns, system performance, degree of satisfaction, complications, and health benefits as perceived by recipients of a surgically implanted neuroprosthesis for exercise, standing, and transfers in individuals with low-cervical or thoracic spinal cord injury (SCI). A standardized telephone survey was administered to 11 recipients of the Case Western Reserve University/Veterans Affairs (CWRU/VA) implanted standing neuroprosthesis with more than 12 months of experience with the functional electrical stimulation (FES) system. Nine implant recipients were using the neuroprosthesis regularly for standing and/or exercising at the time of the survey. All 11 implant recipients noted improved health and a reduced incidence of pressure sores, leg spasms, and urinary tract infections (UTIs). No incidents of deep-vein thrombosis, infection, cellulitis, or electrical burns because of the neuroprosthesis were noted. System recipients uniformly felt that the neuroprosthesis resulted in better overall health and general well-being. Subjects were moderately to very satisfied with the performance of the neuroprosthesis and unanimously expressed a willingness to repeat the surgery and rehabilitation to obtain the same clinical outcome. All implant recipients reported the system to be safe, reliable, and easy to use. The implanted standing neuroprosthesis appears to be a clinically acceptable and effective means of providing the ability to exercise, stand, and transfer to selected individuals with paraplegia or low tetraplegia.

Activities of Daily Living↗