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Biomedical subjects

L M McIntyre

Publications and source records attributed to L M McIntyre.

At least 19 recordsLinked to original sources
PubMed2004

Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila.

Genome-wide microarray analysis (Affymetrix array) was used (i) to determine whether only one gene, the cytochrome P450 enzyme Cyp6g1, is differentially transcribed in dichlorodiphenyltrichloroethane (DDT)-resistant vs. -susceptible Drosophila; and (ii) to profile common genes differentially transcribed across a DDT-resistant field isolate [Rst(2)DDT(Wisconsin)] and a laboratory DDT-selected population [Rst(2)DDT(91-R)]. Statistical analysis (ANOVA model) identified 158 probe sets that were differentially transcribed among Rst(2)DDT(91-R), Rst(2)DDT(Wisconsin), and the DDT-susceptible genotype Canton-S (P < 0.01). The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene (Dbi) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila, and this difference was significant at the most stringent statistical level, a Bonferroni correction. The list of potential candidates differentially transcribed also includes 63 probe sets for which molecular function ontology annotation of the probe sets did not exist. A total of four genes (Cyp6a2, Dbi, Uhg1, and CG11176) were significantly different (P < 5.6 e(-06)) between Rst(2)DDT(91-R) and Canton-S. Additionally, two probe sets encoding Cyp12d1 and Dbi were significantly different between Rst(2)DDT(Wisconsin) and Canton-S after a Bonferroni correction. Fifty-two probe sets, including those associated with pesticide detoxification, ion transport, signal transduction, RNA transcription, and lipid metabolism, were commonly expressed in both resistant lines but were differentially transcribed in Canton-S. Our results suggest that more than Cyp6g1 is overtranscribed in field and laboratory DDT-resistant genotypes, and the number of commonalities suggests that similar resistance mechanisms may exist between laboratory- and field-selected DDT-resistant fly lines.

Animals↗
PubMed2004

Expression profile analysis of wild-type and fcc1 mutant strains of Fusarium verticillioides during fumonisin biosynthesis.

Fusarium verticillioides produces a group of mycotoxins known as fumonisins that are associated with a variety of mycotoxicoses in humans and animals. In this study, DNA microarrays were constructed with expressed sequence tags (ESTs) from F. verticillioides. To identify genes with patterns of expression similar to the fumonisin biosynthetic (FUM) genes, the microarray was probed with labeled cDNAs originating from a wild-type strain and a fcc1 mutant grown on maize and in a defined medium adjusted to either pH 3 or pH 8. The comparative analyses revealed differential expression of genes corresponding to 116 ESTs when the fungal strains were grown on maize. Under different pH conditions, 166 ESTs were differentially expressed, and 19 ESTs were identified that displayed expression patterns similar to the FUM ESTs. These results provide candidate genes with potential roles in fumonisin biosynthesis.

Expressed Sequence Tags↗
PubMed2002

Combining mapping and arraying: An approach to candidate gene identification.

A combination of quantitative trait locus (QTL) mapping and microarray analysis was developed and used to identify 34 candidate genes for ovariole number, a quantitative trait, in Drosophila melanogaster. Ovariole number is related to evolutionary fitness, which has been extensively studied, but for which few a priori candidate genes exist. A set of recombinant inbred lines were assayed for ovariole number, and QTL analyses for this trait identified 5,286 positional candidate loci. Forty deletions spanning the QTL were employed to further refine the map position of genes contributing to variation in this trait between parental lines, with six deficiencies showing significant effects and reducing the number of positional candidates to 548. Parental lines were then assayed for expression differences by using Affymetrix microarray technology, and ANOVA was used to identify differentially expressed genes in these deletions. Thirty-four genes were identified that showed evidence for differential expression between the parental lines, one of which was significant even after a conservative Bonferroni correction. The list of potential candidates includes 5 genes for which previous annotations did not exist, and therefore would have been unlikely choices for follow-up from mapping studies alone. The use of microarray technology in this context allows an efficient, objective, quantitative evaluation of genes in the QTL and has the potential to reduce the overall effort needed in identifying genes causally associated with quantitative traits of interest.

Analysis of Variance↗
PubMed2002

The maize Brown midrib1 locus affects cell wall composition and plant development in a dose-dependent manner.

The four brown midrib (bm) mutants of maize have a reduced content and altered subunit composition of the cell wall polymer lignin. The bm mutations have traditionally been considered completely recessive, because the brown midrib phenotype is only apparent in plants homozygous for the mutation. In addition to an effect on cell wall composition, some bm mutations have been shown to affect flowering time. We had preliminary evidence for a dosage effect of the Bm1 locus on flowering time, which prompted this detailed study on the Bm1 locus. In this study, near-isogenic lines (in an A619 background) with zero, one or two bm1 mutant alleles were compared. The bm1 heterozygotes flowered significantly earlier than both the wild-type plants and bm1 mutants. This difference can at least be partly attributed to an accelerated growth rate in the later stages of plant development. Furthermore, Fourier transform infrared spectroscopy revealed that the cell wall composition of the bm1 heterozygous plants is distinct from both the bm1 and wild-type homozygotes. The combination of the data on flowering time and the data on cell wall composition provide evidence for a dosage effect at the Bm1 locus.

Cell Wall↗
PubMed2001

Dementia with Lewy bodies and Alzheimer's disease.

To investigate similarities and differences between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), we undertook a demographic analysis of 277 patients from the Kathleen Price Bryan Brain Bank with an antemortem diagnosis of probable AD. Patients with additional, possibly confounding clinical and pathologic diagnoses such as infarcts, hematomas, neoplasms, and other neurodegenerative disorders, were excluded from the analysis. Neuropathologically, AD alone was present in 192 subjects (69%), and DLB was found in 85 subjects (31%). All of the DLB cases had neuropathologic evidence of AD sufficient to meet CERAD criteria for a diagnosis of definite AD plus nigral Lewy bodies. Gender, apolipoprotein E (APOE) genotype, brain weight, age at death, duration of disease and Braak stage were compared between the two groups. Statistical analyses were performed using Fisher's exact test for comparisons of categorical data and Student's t-test for comparison of means for continuous outcomes. The proportion of males and females was balanced in the combined AD and DLB populations. There was a highly statistically significant increased frequency of APOE 3/4 in males with DLB (P = 0.007). We found higher brain weights in males with DLB versus males with AD (P = 0.012). AD was more frequent in females and DLB was more frequent in males (P = 0.019). Our findings with respect to age at death, duration of disease and Braak stage within diagnostic groups confirm previously reported findings. These data suggest that Lewy bodies are more common in males affected with dementia, especially those with the APOE 3/4 genotype.

Age Factors↗
PubMed2001

Detection and localization of a single binary trait locus in experimental populations.

The advancements made in molecular technology coupled with statistical methodology have led to the successful detection and location of genomic regions (quantitative trait loci; QTL) associated with quantitative traits. Binary traits (e.g. susceptibility/resistance), while not quantitative in nature, are equally important for the purpose of detecting and locating significant associations with genomic regions. Existing interval regression methods used in binary trait analysis are adapted from quantitative trait analysis and the tests for regression coefficients are tests of effect, not detection. Additionally, estimates of recombination that fail to take into account varying penetrance perform poorly when penetrance is incomplete. In this work a complete probability model for binary trait data is developed allowing for unbiased estimation of both penetrance and recombination between a genetic marker locus and a binary trait locus for backcross and F2 experimental designs. The regression model is reparameterized allowing for tests of detection. Extensive simulations were conducted to assess the performance of estimation and testing in the proposed parameterization. The proposed parameterization was compared with interval regression via simulation. The results indicate that our parameterization shows equivalent estimation capabilities, requires less computational effort and works well with only a single marker.

Animals↗
PubMed2001

Measuring patient expectations: does the instrument affect satisfaction or expectations?

BACKGROUND: Fulfillment of patients' expectations may influence health care utilization, affect patient satisfaction, and be used to indicate quality of care. Several different instruments have been used to measure expectations, yet little is known about how different assessment methods affect outcomes. OBJECTIVE: The object of the study was to determine whether different measurement instruments elicit different numbers and types of expectations and different levels of patient satisfaction. DESIGN: Patients waiting to see their physician were randomly assigned to receive 1 of 2 commonly used instruments assessing expectations or were assigned to a third (control) group that was not asked about expectations. After the visit, patients in all 3 groups were asked about their satisfaction and services they received. SUBJECTS: The study subjects were 290 male, primary care outpatients in a VA general medicine clinic. MEASURES: A "short" instrument asked about 3 general expectations for tests, referrals, and new medications, while a "long" instrument nested similar questions within a more detailed list. Wording also differed between the 2 instruments. The short instrument asked patients what they wanted; the long instrument asked patients what they thought was necessary for the physician to do. Satisfaction was measured with a visit-specific questionnaire and a more general assessment of physician interpersonal skills. RESULTS: Patients receiving the long instrument were more likely to express expectations for tests (83% vs. 28%, P <0.001), referrals (40% vs. 18%, P <0.001), and new medications (45% vs. 28%, P <0.001). The groups differed in the number of unmet expectations: 40% of the long instrument group reported at least 1 unmet expectation compared with 19% of the short instrument group (P <0.001). Satisfaction was similar among the 3 groups. CONCLUSIONS: These different instruments elicit different numbers of expectations but do not affect patient satisfaction.

Ambulatory Care Facilities↗
PubMed2000

Incidence of stroke and season of the year: evidence of an association.

Evidence of seasonal variation in the incidence of stroke is inconsistent. This may be a likely consequence of one or more methodological shortcomings of the studies investigating this issue, including inappropriate analytic models, insufficient length of time, small sample size, and a regional (vs. national) focus. The authors' objective was to ascertain whether an association exists between season of the year and the incidence of stroke by using a methodological approach designed to overcome these limitations. The authors used a longitudinal study design involving 72,779 veterans hospitalized for stroke at any Veterans Affairs hospital nationally during the years 1986-1995. These data were analyzed by using time series methods. There was clear evidence of a seasonal occurrence for stroke in general. This seasonal effect was found for ischemic stroke, but not for hemorrhagic stroke. The peak occurrence was in mid-May. Neither the region (i.e., climate) nor the race of the patient substantially modified the seasonal trend. An explanation for this pattern remains to be determined.

Adult↗
PubMed2000

In vitro resistance to thrombin-induced platelet microbicidal protein in isolates of Staphylococcus aureus from endocarditis patients correlates with an intravascular device source.

Platelet microbicidal proteins (PMPs) are small antimicrobial peptides secreted by mammalian platelets. In vitro resistance of Staphylococcus aureus strains to PMPs correlates with more extensive disease in experimental infective endocarditis (IE). To determine whether this same relationship exists in human S. aureus IE, we evaluated the in vitro PMP susceptibility phenotype of isolates from 58 prospectively-identified patients with definite S. aureus IE. On multivariate analyses, patients with S. aureus IE complicating an infected intravascular device were significantly more likely to have IE caused by a PMP-resistant strain (P=.0193). No correlations were detected between in vitro PMP resistance among S. aureus strains and the severity of human IE. This work supports the concept that in vitro PMP resistance in clinical S. aureus strains is associated with important clinical characteristics of S. aureus endovascular infections in vivo.

Analysis of Variance↗
PubMed2000

In search of a good death: observations of patients, families, and providers.

Despite a recent increase in the attention given to improving end-of-life care, our understanding of what constitutes a good death is surprisingly lacking. The purpose of this study was to gather descriptions of the components of a good death from patients, families, and providers through focus group discussions and in-depth interviews. Seventy-five participants-including physicians, nurses, social workers, chaplains, hospice volunteers, patients, and recently bereaved family members-were recruited from a university medical center, a Veterans Affairs medical center, and a community hospice. Participants identified six major components of a good death: pain and symptom management, clear decision making, preparation for death, completion, contributing to others, and affirmation of the whole person. The six themes are process-oriented attributes of a good death, and each has biomedical, psychological, social, and spiritual components. Physicians' discussions of a good death differed greatly from those of other groups. Physicians offered the most biomedical perspective, and patients, families, and other health care professionals defined a broad range of attributes integral to the quality of dying. Although there is no "right" way to die, these six themes may be used as a framework for understanding what participants tend to value at the end of life. Biomedical care is critical, but it is only a point of departure toward total end-of-life care. For patients and families, psychosocial and spiritual issues are as important as physiologic concerns.

Adult↗
PubMed2000

Circumventing multiple testing: a multilocus Monte Carlo approach to testing for association.

Advances in marker technology have made a dense marker map a reality. If each marker is considered separately, and separate tests for association with a disease gene are performed, then multiple testing becomes an issue. A common solution uses a Bonferroni correction to account for multiple tests performed. However, with dense marker maps, neighboring markers are tightly linked and may have associated alleles; thus tests at nearby marker loci may not be independent. When alleles at different marker loci are associated, the Bonferroni correction may lead to a conservative test, and hence a power loss. As an alternative, for tests of association that use family data, we propose a Monte Carlo procedure that provides a global assessment of significance. We examine the case of tightly linked markers with varying amounts of association between them. Using computer simulations, we study a family-based test for association (the transmission/disequilibrium test), and compare its power when either the Bonferroni or Monte Carlo procedure is used to determine significance. Our results show that when the alleles at different marker loci are not associated, using either procedure results in tests with similar power. However, when alleles at linked markers are associated, the test using the Monte Carlo procedure is more powerful than the test using the Bonferroni procedure. This proposed Monte Carlo procedure can be applied whenever it is suspected that markers examined have high amounts of association, or as a general approach to ensure appropriate significance levels and optimal power.

Alleles↗
PubMed2000

Racial variation in wanting and obtaining mental health services among women veterans in a primary care clinic.

Epidemiologic studies suggest that African-American women may be less likely to obtain mental health services. Racial differences were explored in wanting and obtaining mental health services among women in an equal access primary care clinic setting after adjusting for demographics, mental disorder symptoms, and a history of sexual trauma. Participating in the study were women veterans at a primary care clinic at the Durham Veterans Affairs Medical Center. Consecutive women patients (n = 526) between the ages of 20 and 49 years were screened for a desire to obtain mental health services. Patients were given the Primary Care Evaluation of Mental Disorders questionnaire (PRIME-MD) and a sexual trauma questionnaire. Mental health service utilization was monitored for 12 months. The median age of the women was 35.8 years; 54.4% of them were African-American. African-American women expressed a greater desire for mental health services than whites, yet mental health resources at the clinic were similarly used by both racial groups. African-American women may want more mental health services; however, given an equal access system, there were no racial differences in mental health use.

Adult↗
PubMed1999

Time to flowering in brown midrib mutants of maize: an alternative approach to the analysis of developmental traits.

The brown midrib (bm) mutations of maize affect the biosynthesis of lignin, resulting in reddish-brown vascular tissue in the stem, the leaf blade and sheath. Investigating the effects of the change in lignin content and composition on other phenotypic traits in bm mutants is important in increasing the understanding of how secondary metabolism affects plant development. We examined the time to flowering of inbred A619 and near-isogenic lines of bm2, bm1-bm2 and a segregating population with wild-type and bm1 heterozygotes in a controlled experimental design (Latin square) in two locations. Survival analysis was used to describe the distribution of the time to flowering and compare differences between genotypic classes. Survival analysis is a readily accessible technique that can improve inferences in cases where distributions are skewed, or where data are missing or incomplete. The basic approach to survival analysis as well as its specific application to these data is described. After controlling for the effects of the locations, the time to flowering of the bm2 and segregating populations was found to be significantly different from the wild-type and bm1-bm2 populations.

Models, Biological↗
PubMed1999

Validation of a Trauma Questionnaire in veteran women.

The Trauma Questionnaire (TQ) assesses a woman's history of childhood and adult sexual trauma, sexual harassment, and domestic violence. The TQ is used widely at Veterans Affairs Medical Centers, but its validity has not been thoroughly examined. In a prospective study of 127 women, we found the TQ to have good to excellent agreement with a semistructured clinician interview and good sensitivity and specificity. The TQ can be used as a valid alternative to the clinician interview in the initial elicitation of trauma history among women veterans in the primary care setting.

Adult↗
PubMed1998

Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals.

The presence of diffuse or primitive senile plaques in the neocortex of cognitively normal elderly at autopsy has been presumed to represent normal aging. Alternatively, these patients may have developed dementia and clinical Alzheimer disease (AD) if they had survived. In this setting, these patients could be subjects for cognitive or pharmacologic intervention to delay disease onset. We have thus followed a cohort of cognitively normal elderly subjects with a Clinical Dementia Rating (CDR) of 0 at autopsy. Thirty-one brains were examined at postmortem according to Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria and staged according to Braak. Ten patients were pathologically normal according to CERAD criteria (1a). Two of these patients were Braak Stage II. Seven very elderly subjects exhibited a few primitive neuritic plaques in the cortex and thus represented CERAD 1b. These individuals ranged in age from 85 to 105 years and were thus older than the CERAD la group that ranged in age from 72 to 93. Fourteen patients displayed Possible AD according to CERAD with ages ranging from 66 to 95. Three of these were Braak Stage I, 4 were Braak Stage II, and 7 were Braak Stage III. The Apolipoprotein E4 allele was over-represented in this possible AD group. Neuropsychological data were available on 12 individuals. In these 12 individuals, Possible AD at autopsy could be predicted by cognitive deficits in 1 or more areas including savings scores on memory testing and overall performance on some measures of frontal executive function.

Aged↗
PubMed1997

Hardy-Weinberg testing for continuous data.

Estimation of allelic and genotypic distributions for continuous data using kernel density estimation is discussed and illustrated for some variable number of tandem repeat data. These kernel density estimates provide a useful representation of data when only some of the many variants at a locus are present in a sample. Two Hardy-Weinberg test procedures are introduced for continuous data: a continuous chi-square test with test statistic T(CCS) and a test based on Hellinger's distance with test statistic T(HD). Simulations are used to compare the powers of these tests to each other and to the powers of a test of intraclass correlation T(IC), as well as to the power of Fisher's exact test T(FET) applied to discretized data. Results indicate that the power of T(CCS) is better than that of T(HD), but neither is as powerful as T(FET). The intraclass correlation test does not perform as well as the other tests examined in this article.

Alleles↗
PubMed1990

13C and 31P NMR studies of the pentose phosphate pathway in human erythrocytes.

31P NMR was used to monitor the concentrations of some of the intermediates of the non-oxidative pentose phosphate pathway (PPP) during the dissimilation of inosine and phosphate in dilute haemolysates. The temperature dependence of the ketone/hydrate ratio in dihydroxyacetone phosphate and the relative proportions of the isomers of sedoheptulose 1,7-bisphosphate were measured. The 31P NMR time courses were compared with the simulations obtained with a computer model of the modified F-type PPP.

Aldose-Ketose Isomerases↗