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M B Miller

Publications and source records attributed to M B Miller.

At least 19 recordsLinked to original sources
PubMed2006

Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus: support for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology Network participants.

AIMS/HYPOTHESIS: While there are sex-related differences in both the prevalence of type 2 diabetes mellitus and disease risk factors, there is only limited research on sex-specific influences on type 2 diabetes aetiology within the same study population. Thus, we assessed genotype-by-sex interaction using a liability threshold model in an attempt to localise sex-specific type 2 diabetes quantitative trait loci (QTLs). SUBJECTS, MATERIALS AND METHODS: Hypertensive siblings and their offspring and/or parents in the Hypertension Genetic Epidemiology Network of the Family Blood Pressure Program were recruited from five field centres. The diabetic phenotype was adjusted for race, study centre, age and non-linear age effects. In total, 567 diabetic individuals were identified in 385 families. Variance component linkage analyses in the combined sample and stratified by sex and race were performed (SOLAR program) using race-specific marker allele frequencies derived from a random sample of participants at each centre. RESULTS: We observed a QTL-specific genotype-by-sex interaction (p=0.009) on chromosome 17 at 31 cM, with females displaying a robust adjusted logarithm of odds (LOD) of 3.0 compared with 0.2 in males and 1.3 in the combined sample. Three additional regions demonstrating suggestive evidence for linkage were detected: chromosomes 2 and 5 in the female sample and chromosome 22 (adjusted LOD=1.9) in the combined sample. CONCLUSIONS/INTERPRETATION: These findings suggest that multiple genes may regulate susceptibility to type 2 diabetes, demonstrating the importance of considering the interaction of genes and environment in the aetiology of common complex traits.

Adult↗
PubMed2006

Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associated Treatment Study.

In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the alpha-adducin Gly460Trp polymorphism was typed (n=36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype (P=0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender-gene-treatment interaction, P=0.002). The alpha-adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for hypertension treatment.

Aged↗
PubMed2006

Bilateral hematogenous Pseudomonas aeruginosa endophthalmitis after lung transplantation.

Pseudomonas aeruginosa commonly colonizes the airways of patients with cystic fibrosis (CF). However, the occurrence of bacteremia with metastatic infection to the eye causing endogenous endophthalmitis is very rare. In the setting of lung transplantation, the significance of P. aeruginosa bacteremia in patients with CF whose airways are colonized before transplantation is unknown. We report a case of bilateral P. aeruginosa endogenous endophthalmitis in a patient with CF after lung transplant without documented bacteremia. The patient presented with acute eye symptoms in the presence of a left atrial thrombus and the disease followed a rapidly progressive course requiring aggressive medical-surgical treatment. Typically P. aeruginosa endophthalmitis has been associated with a poor visual prognosis. However, with combined medical-surgical management this patient retained useful vision in one eye without having retinal detachment or requiring enucleation. Endogenous endophthalmitis should be considered in the differential diagnosis of ocular complaints in patients with CF after lung transplant.

Adult↗
PubMed2005

Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: the HyperGEN study.

OBJECTIVE: To conduct a full genome search for genes potentially influencing two related phenotypes: body mass index (BMI, kg/m2) and percent body fat (PBF) from bioelectric impedance in men and women. DESIGN: A total of 3383 participants, 1348 men and 2035 women; recruitment was initiated with hypertensive sibpairs and expanded to first-degree relatives in a multicenter study of hypertension genetics. MEASUREMENTS: Genotypes for 387 highly polymorphic markers spaced to provide a 10 cM map (CHLC-8) were generated by the NHLBI Mammalian Genotyping Service (Marshfield, WI, USA). Quantitative trait loci for obesity phenotypes, BMI and PBF, were examined with a variance components method using SOLAR, adjusting for hypertensive status, ethnicity, center, age, age2, sex, and age2 x sex. As we detected a significant genotype-by-sex interaction in initial models and because of the importance of sex effects in the expression of these phenotypes, models thereafter were stratified by sex. No genotype-by-ethnicity interactions were found. RESULTS: A QTL influencing PBF in women was detected on chromosome12q (12q24.3-12q24.32, maximum empirical LOD score=3.8); a QTL influencing this phenotype in men was found on chromosome 15q (15q25.3, maximum empirical LOD score=3.0). These QTLs were detected in African-American and white women (12q) and men (15q). QTLs influencing both BMI and PBF were found over a broad region on chromosome 3 in men. QTLs on chromosomes 3 and 12 were found in the combined sample of men and women, but with weaker significance. CONCLUSION: The locations with highest LOD scores have been previously reported for obesity phenotypes, indicating that at least two genomic regions influence obesity-related traits. Furthermore, our results indicate the importance of considering context-dependent effects in the search for obesity QTLs.

Adult↗
PubMed2001

Brain activations associated with shifts in response criterion on a recognition test.

Sensitivity and bias can be manipulated independently on a recognition test. The goal of this fMRI study was to determine whether neural activations associated with manipulations of a decision criterion would be anatomically distinct from neural activations associated with manipulations of memory strength and episodic retrieval. The results indicated that activations associated with shifting criteria (a manipulation of bias) were located in bilateral regions of the lateral cerebellum, lateral parietal lobe, and the dorsolateral prefrontal cortex extending from the supplementary motor area. These regions were anatomically distinct from activations in the prefrontal cortex produced during memory-based retrieval processes (manipulations of sensitivity), which tended to be more medial and anterior. These later activations are consistent with previous studies of episodic retrieval. Determining patterns of neural activations associated with decision-making processes relative to memory processes has important implications for Cognitive Neuroscience, including the use of these patterns to compare memory models in different paradigms.

Adolescent↗
PubMed2001

Quorum sensing in bacteria.

Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. In general, Gram-negative bacteria use acylated homoserine lactones as autoinducers, and Gram-positive bacteria use processed oligo-peptides to communicate. Recent advances in the field indicate that cell-cell communication via autoinducers occurs both within and between bacterial species. Furthermore, there is mounting data suggesting that bacterial autoinducers elicit specific responses from host organisms. Although the nature of the chemical signals, the signal relay mechanisms, and the target genes controlled by bacterial quorum sensing systems differ, in every case the ability to communicate with one another allows bacteria to coordinate the gene expression, and therefore the behavior, of the entire community. Presumably, this process bestows upon bacteria some of the qualities of higher organisms. The evolution of quorum sensing systems in bacteria could, therefore, have been one of the early steps in the development of multicellularity.

4-Butyrolactone↗
PubMed2000

The left hemisphere's role in hypothesis formation.

In a probability guessing experiment, subjects try to guess which of two events will occur next. Humans tend to match the frequency of previous occurrences in their guesses. Animals other than humans tend to maximize or always choose the option that has occurred the most frequently in the past. Investigators have argued that frequency matching results from the attempt of humans to find patterns in sequences of events even when told the sequences are random. There is independent evidence that the left hemisphere of humans houses a cognitive mechanism that tries to make sense of past occurrences. We performed a probability guessing experiment with two split-brain patients and found that they approximated frequency matching in their left hemispheres and approached maximizing in their right hemispheres. We obtained a conceptual replication of that finding on patients with unilateral damage to either the left or right hemisphere. We conclude that the neural processes responsible for searching for patterns in events are housed in the left hemisphere.

Concept Formation↗
PubMed2000

A longitudinal study of high scorers on the hypomanic personality scale.

Former college students (n = 36) identified by high scores on the Hypomanic Personality Scale (HYP; Eckblad & Chapman, 1986) were compared with control participants (n = 31) at a 13-year follow-up assessment. As hypothesized, the HYP group reported more bipolar disorders and major depressive episodes than the control group. The HYP group also exceeded the control group on the severity of psychotic-like experiences, symptoms of borderline personality disorder, and rates of substance use disorders. HYP group members with elevated scores on the Impulsive-Nonconformity Scale (Chapman et al., 1984) experienced greater rates of bipolar mood disorders, poorer overall adjustment, and higher rates of arrest than the remaining HYP or control participants.

Adult↗
PubMed1999

Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production.

In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. Quorum-sensing bacteria produce, release, and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. In the marine bacterium Vibrio harveyi two parallel quorum-sensing systems exist, and each is composed of a sensor-autoinducer pair. V. harveyi reporter strains capable of detecting only autoinducer 1 (AI-1) or autoinducer 2 (AI-2) have been constructed and used to show that many species of bacteria, including Escherichia coli MG1655, E. coli O157:H7, Salmonella typhimurium 14028, and S. typhimurium LT2 produce autoinducers similar or identical to the V. harveyi system 2 autoinducer AI-2. However, the domesticated laboratory strain E. coli DH5alpha does not produce this signal molecule. Here we report the identification and analysis of the gene responsible for AI-2 production in V. harveyi, S. typhimurium, and E. coli. The genes, which we have named luxSV.h., luxSS.t., and luxSE.c. respectively, are highly homologous to one another but not to any other identified gene. E. coli DH5alpha can be complemented to AI-2 production by the introduction of the luxS gene from V. harveyi or E. coli O157:H7. Analysis of the E. coli DH5alpha luxSE.c. gene shows that it contains a frameshift mutation resulting in premature truncation of the LuxSE.c. protein. Our results indicate that the luxS genes define a new family of autoinducer-production genes.

4-Butyrolactone↗
PubMed1999

A family history study of male sexual orientation using three independent samples.

Available evidence suggests that male homosexuality is both familial and somewhat heritable and that some cases may be caused by an X-linked gene. However, most studies have recruited subjects in a relatively unsystematic manner, typically via advertisements, and hence suffer from the potential methodological flaw of ascertainment bias due to volunteer self-selection. In the present study we assessed the familiality of male homosexuality using two carefully ascertained samples and attempted to replicate findings consistent with X-linkage in three samples. The percentage of siblings of the probands rated as either homosexual or bisexual, with a high degree of certainty, ranged from 7 to 10% for brothers and 3 to 4% for sisters. These estimates are higher than recent comparable population-based estimates of homosexuality, supporting the importance of familial factors for male homosexuality. Estimates of lambda s for male homosexuality ranged from 3.0 to 4.0. None of the samples showed a significantly greater proportion of maternal than paternal homosexual uncles or homosexual male maternal first cousins. Although our results differed significantly with those of some prior studies, they do not exclude the possibility of moderate X-linkage for male sexual orientation.

Adolescent↗
PubMed1999

Memory lost and regained following bilateral hippocampal damage.

We present a longitudinal neuropsychological study (31 examinations over a period of 18 months) of patient DE DF demonstrated bilateral atrophy of the hippocampal formation and globus pallidus resulting from carbon monoxide poisoning. Eighteen months after the event, the volume of the hippocampal formation was reduced by 42% on the left side and 28% on the right. The patient initially presented with a severe global amnesia. Then, he showed a gradual, yet selective recovery of episodic memory function. Verbal free recall and spatial memory performance remained reduced, whereas immediate word recall and recognition memory, as well as picture learning and memory, improved to levels at the lower range of normal performance. Interestingly, nonspatial associative learning was never much impaired and recovered completely by the end of testing. These data are taken as evidence that the human hippocampal formation does not equally support different forms of episodic memory.

Adult↗
PubMed1998

Creating false memories for visual scenes.

Creating false memories has become an important tool to investigate the processes underlying true memories. In the course of investigating the constructive and/or reconstructive processes underlying the formation of false memories, it has become clear that paradigms are needed that can create false memories reliably in a variety of laboratory settings. In particular, neuroimaging techniques present certain constraints in terms of subject response and timing of stimuli that a false memory paradigm needs to comply with. We have developed a picture paradigm which results in the false recognition of items of a scene which did not occur almost as often as the true recognition of items that did occur. It uses a single presentation of pictures with thematic, stereotypical scenes (e.g. a beach scene). Some of the exemplars from the scene were removed (e.g. a beach ball) and used as lures during an auditory recognition test. Subjects' performance on this paradigm was compared with their performance on the word paradigm reintroduced by Roediger and McDermott. The word paradigm has been useful in creating false memories in several neuroimaging studies because of the high frequency of false recognition for critical lures (words not presented but closely associated with lists of words that were presented) and the strong subjective sense of remembering accompanying these false recognitions. However, it has several limitations including small numbers of lures and a particular source confusion. The picture paradigm avoids these limitations and produces identical effects on normal subjects.

Adolescent↗
PubMed1998

Arrhythmias associated with drug toxicity.

Cardiac arrhythmias may result from poisoning by a variety of agents. Although some cardiac disturbances are of limited concern, others occur because of the specific cardiac properties of the ingested drugs, and require specific antidotes. Clinicians must understand the resultant pathophysiology so that therapy is appropriate. This article focuses on drugs that cause ventricular arrhythmias and bradyarrhythmias.

Adrenergic beta-Antagonists↗