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Biomedical subjects

Christopher M Ryan

Publications and source records attributed to Christopher M Ryan.

At least 19 recordsLinked to original sources
PubMed2006

Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing.

Hypertension is a risk factor for diffuse brain atrophy. Yet, there is little evidence that higher blood pressure predicts focal brain atrophy, as indicated by a lower volume of regional brain tissue. This voxel-based morphometry study tested (a) whether higher blood pressure predicts lower regional grey or white matter volume and (b) whether a blood-pressure-related reduction in regional brain tissue volume predicts poorer neuropsychological test performance. Participants were 76 men (M age = 61.33, SD = 4.95 years) and 58 women (M age = 59.86, SD = 5.10 years) without a cardiovascular, cerebrovascular, or neuropsychiatric disease. Results showed that among men, higher resting systolic blood pressure predicted lower grey matter volume in the supplementary motor area and adjacent superior frontal gyrus, the anterior cingulate cortex, and middle temporal gyrus. Among men, lower grey matter volume in the supplementary motor area also predicted a slower time to complete the Trail Making Part B Test of executive control and a poorer recall of items from the Four-word Short-term Memory Test of working memory. These relationships were independent of age, total brain tissue volume, educational history, severity of carotid atherosclerosis, and the extent of periventricular and subcortical white matter lesions. Among women, no statistically significant relationships were found between blood pressure, regional brain tissue volume, and cognitive function. These findings suggest a functional relationship among men between higher blood pressure, lower regional grey matter volume, and poorer cognitive function that is independent of other risk factors and confounding medical conditions.

Aged↗
PubMed2006

Cognitive impairment associated with adjuvant therapy in breast cancer.

The purpose of this study was to determine whether cognitive function changes over time in women with breast cancer who received adjuvant therapy as compared to women with breast cancer who received no adjuvant therapy. Three groups of women (n = 46) were studied; groups 1 and 2 consisted of women with stage I or II breast cancer. Group 1 received chemotherapy and group 2 received chemotherapy plus tamoxifen. Group 3 consisted of women with ductal carcinoma in situ who received no chemotherapy or tamoxifen. Cognitive function was evaluated at three timepoints. Time 1 occurred after surgery and before chemotherapy initiation in groups 1 and 2. Time 1 for group 3 occurred post-surgery. Time 2 occurred within 1 week after the conclusion of chemotherapy for groups 1 and 2 and at a comparable time for group 3. Time 3 occurred 1 year after Time 2. Women who received chemotherapy plus tamoxifen exhibited deterioration on measures of visual memory and verbal working memory and reported more memory complaints. Women who received chemotherapy alone also exhibited deteriorations in verbal working memory. Conversely, cognitive function scores improved in women who received no therapy, indicating practice effects. In conclusion, adjuvant chemotherapy in women with breast cancer can be associated with deteriorations in memory and this may persist over time. The addition of tamoxifen may lead to more widespread memory deficits.

Adult↗
PubMed2006

Body position affects manual dexterity.

To evaluate the relationship between posture and psychomotor efficiency, 20 anesthesia providers performed a test requiring manual dexterity and eye-hand coordination while seated, kneeling, and standing bent forward at the waist. Performance on the Grooved Pegboard Test improved 6%-10% (P < 0.005) when subjects were seated compared to kneeling and standing bent at the waist, positions that the subjects rated as more painful and less comfortable than sitting. Sitting improved manual dexterity more in subjects with poor scores than it did in subjects with good performance. This study demonstrates improved manual dexterity in subjects seated in a comfortable position.

Adult↗
PubMed2006

Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry.

The effects of type 1 diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an age-matched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure.

Adolescent↗
PubMed2006

Improving metabolic control leads to better working memory in adults with type 2 diabetes.

OBJECTIVE: The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance. RESEARCH DESIGN AND METHODS: This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery. RESULTS: Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1-2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG. CONCLUSIONS: Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.

Adult↗
PubMed2005

Biphasic decay of guide RNAs in Trypanosoma brucei.

Guide RNAs (gRNAs) are short mitochondrially encoded RNAs that contain the information for editing of messenger RNAs in Trypanosoma brucei. Although a great deal of work has focused on the utilization of gRNAs in editing, little is known about the turnover of gRNAs. In this report, we utilized in organello pulse chase and in vitro RNA decay experiments to directly examine gRNA turnover. We found that gRNAs are degraded by a biphasic mechanism. In the first step of decay, 3' gRNA sequences encompassing primarily the post-transcriptionally added oligo(U) tail are rapidly removed. This is followed by a second step, which entails a comparatively slower degradation of the encoded gRNA body. Decay of the 3' end of the gRNA is sequence specific, as it does not occur on oligoadenylated gRNAs. In contrast, the nucleotide composition of the 3' extension does not affect the rate of degradation during the second, slower, decay step. Finally, competition assays suggest that complete gRNA decay is mediated by two distinct enzymes, one of which simultaneously recognizes elements of the oligo(U) tail and the encoded portion of the gRNA. Overall, these results provide the first evidence for a gRNA-specific decay pathway.

Animals↗
PubMed2005

Diabetes, aging, and cognitive decline.

Type 1 diabetes is associated with cognitive changes in children and adults, but the extent to which cognition declines with increasing age, and increasing duration of diabetes, remains poorly understood. This cross-sectional study assessed neuropsychological performance on 200 diabetic and 175 nondiabetic adults, 18-64 years of age, stratified into five age bands. Similar age-related cognitive declines were seen on measures of problem-solving, learning and memory, and psychomotor speed, but it was only on the latter measure that diabetic and nondiabetic subjects differed significantly. The best predictor of psychomotor slowing was the presence of clinically significant biomedical complications, particularly proliferative retinopathy, peripheral neuropathy, and peripheral vascular disease (PVD). It now appears that psychomotor slowing is the fundamental cognitive deficit associated with diabetes mellitus; why other cognitive skills are relatively unaffected remains poorly understood.

Adolescent↗
PubMed2005

UTP-dependent turnover of Trypanosoma brucei mitochondrial mRNA requires UTP polymerization and involves the RET1 TUTase.

Trypanosoma brucei mitochondria possess a unique RNA decay pathway in which rapid degradation of polyadenylated mRNAs is dependent on the addition of UTP, as measured by in organello pulse chase assays. To determine the mechanism by which UTP stimulates the degradation of polyadenylated RNAs, we performed in organello pulse chase assays under different conditions. Treatment of mitochondria with proteinase K revealed that UTP does not act through a receptor on the surface of the mitochondria. To determine if the UTP-stimulated RNA decay pathway is triggered by the mitochondrial energy state or ATP:UTP ratio, increasing ATP was added to a constant amount of UTP during the chase period of the assay. Results indicate that rapid turnover is responsive to UTP and not the ATP:UTP ratio. Experiments using UTP analogs demonstrate that UTP polymerization into RNAs is necessary for UTP-dependent degradation. Furthermore, experiments performed with RNAi cells indicate that the RET1 terminal uridylyl transferase (TUTase) is required for UTP-dependent decay of polyadenylated RNAs. Overall, these results show that degradation of polyadenylated RNAs in T. brucei mitochondria can occur through a unique mechanism that requires the polymerization of UTP into RNAs, presumably by the RET1 TUTase.

Animals↗
PubMed2004

Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults.

PURPOSE: In our initial study of the potential effects of cholesterol-lowering interventions on cognitive functioning, treatment with lovastatin as compared with placebo caused performance decrements on several neuropsychological tests, whereas scores on other tests were unaffected. The current study was designed to confirm and extend those findings. METHODS: The study comprised 308 hypercholesterolemic adults between 35 and 70 years of age. Employing a randomized double-blind design, we assigned participants to daily treatment with placebo, 10 mg of simvastatin, or 40 mg of simvastatin for 6 months. A neuropsychological test battery was administered to assess cognitive functioning at baseline and at the end of the treatment period. RESULTS: A total of 283 subjects completed the study: 94 subjects on placebo, 96 taking 10 mg of simvastatin, and 93 taking 40 mg of simvastatin. Compared with placebo, decremental effects of simvastatin treatment were found on tests previously observed to be sensitive to statins (P = 0.008; difference in summary z scores = 0.18; 95% confidence interval [CI]: 0.07 to 0.29) and on tests not previously administered (P = 0.04; difference in summary z scores = 0.17; 95% CI: 0.05 to 0.29), but not on tests previously observed to be insensitive to statins (P = 0.84; difference in summary z scores = 0.02; 95% CI: -0.07 to 0.10). For the three tests specifically affected by simvastatin, effects on cognitive performance were small, manifest only as failure to improve during the 6 months of treatment (compared with placebo), and were confounded by baseline differences on one test. CONCLUSION: This study provides partial support for minor decrements in cognitive functioning with statins. Whether such effects have any long-term sequelae or occur with other cholesterol-lowering interventions is not known.

Adult↗
PubMed2004

TbDSS-1, an essential Trypanosoma brucei exoribonuclease homolog that has pleiotropic effects on mitochondrial RNA metabolism.

Mitochondrial gene expression in trypanosomes is controlled primarily at the levels of RNA processing and RNA stability. This regulation undoubtedly involves numerous ribonucleases. Here we characterize the Trypanosoma brucei homolog of the yeast DSS-1 mitochondrial exoribonuclease, which we term TbDSS-1. Biochemical fractionation indicates that TbDSS-1 is mitochondrially localized, as predicted by its N-terminal sequence. In contrast to its yeast homolog, TbDSS-1 does not appear to be associated with mitochondrial ribosomes. Targeted downregulation of TbDSS-1 by RNA interference in procyclic-form T. brucei results in a severe growth defect. In addition, TbDSS-1 depletion leads to a decrease in the levels of never edited cytochrome oxidase subunit I (COI) mRNA and both unedited and edited COIII mRNAs, indicating this enzyme functions in the control of mitochondrial RNA abundance. We also observe a considerable reduction in the level of edited apocytochrome b (CYb) mRNA and a corresponding increase in unedited CYb mRNA, suggesting that TbDSS-1 functions, either directly or indirectly, in the control of RNA editing. The abundance of both gCYb[560] and gA6[149] guide RNAs is reduced upon TbDSS-1 depletion, although the reduction in gCYb[560] is much more dramatic. The significant reduction in gCYb levels could potentially account for the observed decrease in CYb RNA editing. Western blot analyses of mitochondrial RNA editing and stability factors indicate that the perturbations of RNA levels observed in TbDSS-1 knock-downs do not result from secondary effects on other mitochondrial proteins. In all, these data demonstrate that TbDSS-1 is an essential protein that plays a role in mitochondrial RNA stability and RNA editing.

Amino Acid Sequence↗
PubMed2004

Psychological and cognitive function: predictors of adherence with cholesterol lowering treatment.

BACKGROUND: Failure to adhere to medication regimes is a significant problem in clinical and research settings yet reliable, consistent identification of key psychosocial predictors remains elusive. Studies of mood and personality related to adherence show mixed results-compliance and objectively measured cognitive function are intuitively related but empirical support is lacking. PURPOSE: This study is a secondary analysis to examine the relations between adherence with a medication regime for lowering serum cholesterol and several domains of psychological and cognitive functioning. METHODS: Participants in the initial study completed a measure of personality and a battery of neuropsychological measures at baseline; anxiety and depression were measured at baseline and at 4-week intervals. Medication adherence was tracked with electronic cap monitors for 24 weeks. RESULTS: Only 23% of the sample was fully adherent to medication regimes at least 80% of the time over the 6-month study period. Conscientiousness, according to the Five Factor Theory of Personality, and estimated IQ remained robust predictors of adherence in hierarchical regression analyses. Depression and anxiety, mental flexibility, and visuospatial-constructional ability were less robust but statistically significant (p <.05) correlates of adherence. CONCLUSIONS: Although results of this analysis explain only a portion of the variance in adherence, they demonstrate the importance of trait psychological and cognitive factors in adherence research.

Adult↗
PubMed2003

Polyadenylation regulates the stability of Trypanosoma brucei mitochondrial RNAs.

Polyadenylation of RNAs plays a critical role in modulating rates of RNA turnover and ultimately in controlling gene expression in all systems examined to date. In mitochondria, the precise mechanisms by which RNAs are degraded, including the role of polyadenylation, are not well understood. Our previous in organello pulse-chase experiments suggest that poly(A) tails stimulate degradation of mRNAs in the mitochondria of the protozoan parasite Trypanosoma brucei (Militello, K. T., and Read, L. K. (2000) Mol. Cell. Biol. 21, 731-742). In this report, we developed an in vitro assay to directly examine the effects of specific 3'-sequences on RNA degradation. We found that a salt-extracted mitochondrial membrane fraction preferentially degraded polyadenylated mitochondrially and non-mitochondrially encoded RNAs over their non-adenylated counterparts. A poly(A) tail as short as 5 nucleotides was sufficient to stimulate rapid degradation, although an in vivo tail length of 20 adenosines supported the most rapid decay. A poly(U) extension did not promote rapid RNA degradation, and RNA turnover was slowed by the addition of uridine residues to the poly(A) tail. To stimulate degradation, the poly(A) element must be located at the 3' terminus of the RNA. Finally, we demonstrate that degradation of polyadenylated RNAs occurs in the 3' to 5' direction through the action of a hydrolytic exonuclease. These experiments demonstrate that the poly(A) tail can act as a cis-acting element to facilitate degradation of T. brucei mitochondrial mRNAs.

Adenosine↗
PubMed2003

Experienced scuba divers in Australia and the United States suffer considerable injury and morbidity.

OBJECTIVE: Scuba diving-specific injuries have been well described. However, the injury experiences of individual divers over long diving careers have rarely been investigated. Our objective was to study the acute and chronic injuries of experienced, recreational scuba divers. METHODS: This was an international, cross-sectional, descriptive postal survey of experienced, recreational scuba divers belonging to diving clubs in Australia and the United States. RESULTS: Seven hundred nine divers were enrolled (346 Australian divers and 363 US divers). Most participants were experienced (mean number of dives, 262) male divers (488; 68.8%) aged 31 to 50 years (425; 59.9%). Mild barotrauma was common. Ear, sinus, and tooth "squeeze" had been experienced on > or = 1 occasion by 369 (52.1%), 245 (34.6%), and 66 (9.2%) divers, respectively. Tympanic membrane (TM) rupture, round/oval window rupture, and subcutaneous emphysema had been experienced by 38 (5.4%), 8 (1.1%), and 5 (0.7%) divers, respectively. No diver reported pneumothorax or arterial gas embolism (AGE); however, 31 divers (4.4%) had suffered decompression sickness (DCS). A wide range of other injuries were reported. Sixteen divers (2.3%) reported permanent disabilities, which largely consisted of hearing loss, tinnitus, and balance disorder. CONCLUSIONS: The majority of experienced divers who responded to the survey had suffered diving-related injuries, mainly barotrauma. Further research and diver education are needed to better document injury rates and minimize serious diving-related injuries and permanent disabilities.

Accidents↗
PubMed2002

Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study.

Animal studies have shown diabetes-induced changes in the state and function of the serotonin neuroreceptor system. Diabetes also has induced structural and functional alterations in hippocampus and been associated with altered hypothalamopituitary adrenal axis regulation. In this study, serotonin-1A (5-HT(1A)) receptor binding was measured in humans with type 2 diabetes (n=6) and healthy controls (n=6), using positron emission tomography (PET) and [carbonyl-11C]WAY 100635. Significantly greater 5-HT(1A) receptor binding was detected in mesial temporal cortex, including hippocampus (P<0.05) for type 2 subjects (relative to controls). Within the type 2 group, glycosylated hemoglobin and stressed plasma cortisol levels were positively correlated (P<0.02). These findings support previous studies that suggest serotonergic underpinnings to the neurobiology of diabetes and have shown diabetes-induced neurological changes in hippocampus.

Adult↗
PubMed2002

Diabetes, the brain, and behavior: is there a biological mechanism underlying the association between diabetes and depression?

In summary, our review of the literature suggests that diabetes, especially type 1 diabetes, may place patients at risk for a depressive disorder through a biological mechanism linking the metabolic changes of diabetes to changes in brain structure and function. Further studies are warranted examining these relationships in order to better understand the impact of diabetes on brain functioning and structure as well as one potential manifestation of such changes--affective disorder. Moreover, such studies could play a useful role in better understanding mechanisms that commonly underlie the development of depression in individuals without diabetes but with other medical problems or conditions.

Behavior↗