Biomedical subjects

Karen J Miller

Publications and source records attributed to Karen J Miller.

10 recordsLinked to original sources

PubMed2006

PET of brain amyloid and tau in mild cognitive impairment.

BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.

Aged↗

PubMed2006

Memory improvement with treatment of hypothyroidism.

The consequences of inadequate thyroid hormone availability to the brain and treatment effects of levothyroxine on cognitive function are still poorly understood. This study prospectively assessed the effects of thyroid replacement therapy on cognitive function in patients suffering from biochemical evidenced, untreated hypothyroidism. Significant effects between the untreated hypothyroid group and control group were limited to verbal memory retrieval. When assessing the effects of 3-month treatment, results revealed that the treated hypothyroid group had significant increased verbal memory retrieval. Results suggest that specific memory retrieval deficits associated with hypothyroidism can resolve after replacement therapy with levothyroxine.

Adolescent↗

PubMed2006

Effects of a 14-day healthy longevity lifestyle program on cognition and brain function.

OBJECTIVE: The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints. METHODS: Seventeen nondemented subjects, aged 35-69 years (mean: 53 years, standard deviation: 10) with mild self-reported memory complaints but normal baseline memory performance scores were randomly assigned to 1) the intervention group (N = 8): a program combining a brain healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise (brain teasers and verbal memory training techniques); or 2) the control group (N = 9): usual lifestyle routine. Pre- and postintervention measures included self-assessments of memory ability, objective tests of cognitive performance, and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS: Subjects in the intervention group objectively demonstrated greater word fluency. Concomitantly, their FDG-PET scans identified a 5% decrease in activity in the left dorsolateral prefrontal cortex. The control group showed no significant change in any of the measures. CONCLUSIONS: A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and healthy diet was associated with significant effects on cognitive function and brain metabolism. Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory.

Adult↗

PubMed2005

Object naming and semantic fluency among individuals with genetic risk for Alzheimer's disease.

OBJECTIVES: This study longitudinally examined the object naming and semantic fluency of individuals who are at risk for developing Alzheimer's disease (AD) by virtue of having APOE-4 or a family history of AD. METHODS: A total of 108 participants (40 with a family history of AD and 43 with APOE-4) completed the Boston Naming Test and the Animal Naming task at initial assessment and after two years. RESULTS: At baseline, object naming was significantly lower for those with both risk factors, F(2, 99) = 5.72, p < 0.01, but those with either risk factor had significantly lower scores at follow-up, F(2, 99) = 3.41, p < 0.05. Semantic fluency (animal naming) was reduced among subjects with the APOE-4 allele at baseline, F(1, 100) = 4.02, p < 0.05, but it was not associated with either risk factor at follow-up. CONCLUSIONS: These deficits may be associated with a prodromal risk for AD and may serve as pre-symptomatic markers for the development of AD.

Aged↗

PubMed2005

Executive functions.

Executive functions are higher-order cognitive processes that continue to develop well into adulthood. They are critically important to behavioral self-control and task performance, and deficits can have serious effects on a student's functioning in many areas. Primary care pediatricians can play an important role by being aware of this evolving field of research, current assessment strategies, and by encouraging families, schools, and students to adopt a positive and problem-solving approach to improve executive functions.

Adolescent↗

PubMed2004

Renal cysts of inv/inv mice resemble early infantile nephronophthisis.

Cystic kidney disease has been linked to mutations in the Invs gene in mice with inversion of embryonic turning (inv/inv) and the INVS (NPHP2) gene in infants with nephronophthisis type 2 (NPHP2). The inv mouse model features multiorgan defects including renal cysts, altered left-right laterality, and hepatobiliary duct malformations transmitted in an autosomal recessive manner. Affected mice usually die of renal and liver failure by postnatal day 7. Although cardiopulmonary and liver anomalies have been carefully detailed, renal cysts have yet to be fully characterized in inv/inv. By use of three-dimensional visualization by two-photon microscopy, this study provides the first comprehensive analysis of in situ cyst formation and progression in inv/inv kidneys. At embryonic day 15, there is dilatation of Bowman's capsule followed temporally by corticomedullary cysts involving collecting ducts, proximal tubules, and thick ascending limbs. Collecting ducts of newborn inv/inv mice are uniformly and diffusely cystic from medulla to cortex, with normal diameters found only at their most proximal tips. Proximal tubules form fusiform cysts that alternate with segments of normal or narrowed caliber along torturous convolutions. Because defective cilia have been linked to situs inversus and cystogenesis, we examined inv/inv cilia by scanning and transmission electron microscopy. The former detected monocilia of expected length in cystic collecting ducts and proximal tubules; the latter demonstrated the usual 9 + 2 pattern in respiratory cilia. The inv mutant mouse has renal cysts resembling infantile NPHP2 and will provide broader insight into the role cilia play in renal cystogenesis.

Animals↗

PubMed2003

The other side of estrogen replacement therapy: outcome study results of mood improvement in estrogen users and nonusers.

The effect of estrogen on the brain and body of women is a controversial topic that has received a tremendous amount of attention in the past few years. Recent reviews have focused on hormone replacement therapy (HRT), medical risks, and effects on brain metabolism, cognition, risk of Alzheimer's disease, and mood. This article summarizes HRT and mood improvement in postmenopausal women. For nondepressed women, experimental designs provide no clear evidence for mood improvement associated with HRT, whereas observational studies are more likely to report mood improvement. There appears to be moderate evidence that HRT facilitates the improvement of clinical depression and the efficacy of antidepressants. Heterogeneity among studies makes it difficult to generalize and recommend HRT for mood improvement in postmenopausal women, but there is a clear need to examine the necessary duration of HRT for neuroprotection to decrease a woman's risk for depression, cognitive dysfunction, and development of Alzheimer's disease.

Affect↗

PubMed2002

Mood symptoms and cognitive performance in women estrogen users and nonusers and men.

OBJECTIVES: Previous studies have suggested sex differences in mood and cognition and that estrogen effects may partially explain such differences. In this study, we explore sex differences for a range of mood symptoms and for neuropsychological performance in men and postmenopausal women and assess the potential influence of estrogen on these measures. DESIGN: Cross-sectional study of men and women examining mood, neuropsychological test data, and estrogen replacement therapy (ERT) use. SETTING: Outpatient study at an urban teaching hospital with subjects recruited from the community. PARTICIPANTS: All subjects (N = 96) were between the ages of 57 and 75 and included 31 women using ERT, 16 non-ERT users, and 49 men. Subjects did not have major depression and were nondemented. MEASUREMENT: The three groups were compared according to profile of mood states and neuropsychological performance, and statistical analyses were controlled for socioeconomic status, age, and education level. RESULTS: Female ERT users were less depressed and less angry and performed better on measures of verbal fluency and working memory than the other subject groups. CONCLUSION: Postmenopausal estrogen use is associated with better mood and cognitive performance on tasks of fluency and working memory. These results suggest that estrogen should be examined as a potentially critical variable influencing late-life sex differences in mood and cognition.

Affect↗

PubMed2002

Synthesis of pyruvate dehydrogenase in Staphylococcus aureus is stimulated by osmotic stress.

The pyruvate dehydrogenase multienzyme complex (PDHC) was found to be upregulated by osmotic stress in the osmotolerant pathogen Staphylococcus aureus. Upregulation was detectable in the levels of both activity and protein and was judged to be about fourfold when sodium chloride was used to adjust the water activity (a(w)) of the growth medium to 0.94. The upregulation of the PDHC was also found to be humectant dependent and was greatest when impermeant, nonmetabolizable humectants were used to adjust a(w). Further experiments provided evidence that in addition to osmotic upregulation, the PDHC complex is also subject to catabolite repression, thus providing a possible explanation for the observation that high concentrations of carbohydrates are generally more inhibitory to the growth of this bacterial pathogen than are high concentrations of salts.

Culture Media↗

PubMed2002

Humectant permeability influences growth and compatible solute uptake by Staphylococcus aureus subjected to osmotic stress.

The effects of different humectants (sodium chloride, sucrose, and glycerol) on the growth of and compatible solute (glycine betaine, proline, and carnitine) uptake by the osmotolerant foodborne pathogen Staphylococcus aureus were investigated. While growth in the presence of the impermeant humectants sodium chloride and sucrose induced the accumulation of proline and glycine betaine by cells, growth in the presence of the permeant humectant glycerol did not. When compatible solutes were omitted from low-water-activity media, growth was very poor in the presence of impermeant humectants. In contrast, the addition of compatible solutes had essentially no effect on growth when cells were grown in low-water-activity media containing glycerol as the humectant. Carnitine was found to accumulate to high intracellular levels in osmotically stressed cells when proline and glycine betaine were absent, making it a potentially important compatible solute for this organism.

Betaine↗