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Biomedical subjects

K A O'Donnell

Publications and source records attributed to K A O'Donnell.

18 recordsLinked to original sources
PubMed2001

Rapid detection of the R408W and I65T mutations in phenylketonuria by glycosylase mediated polymorphism detection.

Mutation detection methods based upon chemical or enzymatic cleavage of DNA offer excellent detection efficiencies coupled with high throughput and low unit cost. We describe the application of the novel technique of Glycosylase Mediated Polymorphism Detection (GMPD) to the detection of two of the most common mutations of the PAH gene in the Irish population that cause phenylketonuria (PKU), R408W and I65T, which occur at relative frequencies of 41.0% and 10.4% respectively. GMPD assays for R408W and I65T were developed permitting fluorescent detection of cleavage products on the ALFexpresstrade mark automated DNA sequencer. The method was validated by screening a panel of PKU patients whose mutant genotypes had previously been characterised by standard methods. It also proved possible to perform multiplex detection of the two mutations by co-electrophoresis of GMPD products. GMPD is a rapid and robust method for the detection of the R408W and I65T mutations, whose key advantage lies in its use of a pair of enzymes with high cleavage efficiency to detect a number of mutations as compared to the use of individual digestions with a range of specific restriction endonuclease enzymes. Hum Mutat 17:432, 2001.

Alleles↗
PubMed2001

Adolescent views of diabetes-related parent conflict and support: a focus group analysis.

PURPOSE: To increase understanding of adolescent-parent diabetes-related conflicts and supports in the management of type 1 diabetes by means of a focus group research approach. METHODS: Twenty-four adolescents (10 boys and 14 girls, age 13-15 years; 97% white) participated in three same-sex focus groups at two diabetes summer camps. The focus group leader used a prepared set of open-ended questions to guide the 90-minute sessions. Sessions were tape-recorded, transcribed, and analyzed by a set procedure for qualitative analysis to identify the adolescents' perspectives on parent-adolescent sources of diabetes-related conflict and support. RESULTS: Adolescents reported the following sources of diabetes-related conflict: parental worry and intrusive behaviors; parental lack of understanding and blaming behaviors, and the parents focus on the future vs. the adolescent focus on the present. With regard to diabetes-related support, the teens identified parental understanding of the demands of diabetes and parental provision of reassurance about their child's illness and normative functioning. CONCLUSIONS: Adolescents' perceptions of parental worry, lack of understanding, and resulting intrusive and blaming behaviors are major areas of conflict that need to be addressed in the management of type 1 diabetes.

Adolescent↗
PubMed2001

High-order perturbation theory for light scattering from a rough metal surface.

The angular distribution of the mean diffuse intensity scattered from a metal surface with one-dimensional roughness is studied with perturbation theory. From an approach based on the reduced Rayleigh equations in p polarization, exact perturbation terms up to eighth order in the height parameter are developed for surface roughness consistent with a stationary Gaussian process. The theory is evaluated for a number of cases in which surface plasmon polariton excitation is significant and produces effects such as backscattering enhancement. For surface roughness having a wide Gaussian power spectrum, it is found that the high-order terms lead to roughness-induced broadening of the backscattering peak. For rectangular spectra, two cases are studied in which backscattering effects are due to sixth- and eighth-order terms; both cases provide good comparisons with previously unexplained experimental results. Further, because of an eighth-order term, the diffuse intensity is shown to contain a specular peak that also relies on polariton excitation. This new effect is studied in detail and is found to arise from the constructive interference of contributions produced by multiple-scattering processes, although the time-reversed paths that produce backscattering enhancement are not essential to the specular effect.

Journal Article↗
PubMed2000

Lipoblastoma: better termed infantile lipoma?

Lipoblastoma is a rare adipose tumor occurring exclusively in childhood. There have been no reports of metastases, making the designation "blastoma" confusing, since this term is usually reserved for malignant tumors. Two recent cases treated at our institution confirm its benign nature. In addition, a review of the literature supports the idea that the tumor may more accurately be described as an "infantile lipoma". Infantile lipoma better reflects many of the tumor's characteristics such as, its early occurrence, it's ability to mature into a simple lipoma, it's cellular composition of mainly mature adipocytes, and its benign course. Although lipoblastoma is an uncommonly encountered tumor, making an effort to change its name to infantile lipoma will result in a more a accurate term that will facilitate treatment.

Abdominal Neoplasms↗
PubMed1999

Preservation of prefrontal cortical volume in behaviorally characterized aged macaque monkeys.

Normal aging is frequently accompanied by a decline in cognitive capacities supported by the prefrontal cortex. The principal aim of the present study was to determine whether these impairments are coupled to morphometric alterations affecting the volume of the prefrontal cortex in an established nonhuman primate model. A large sample of 19 young (4-11 years old) and 40 aged (20-32 years old) rhesus monkeys was tested using a delayed response procedure known to require the functional integrity of area 46 of the prefrontal cortex. Aged monkeys displayed robust delayed response deficits that were specifically related to the demands of testing on memory. Modern stereological methods were then used to estimate the total volume of area 46 and the volume of layer I in brains from 21 young and aged monkeys. Prefrontal cortex volume was entirely preserved in the aged monkeys as a group and among the subset of aged subjects that displayed the most severe behavioral impairment. These findings indicate that gross morphometric alterations affecting cortical volume are unlikely to account for age-related decline in the information processing capacities of area 46 in primates. Taken together, current evidence instead suggests that changes in the functional connectivity of critical cortical circuits may contribute to normal cognitive aging.

Aging↗
PubMed1999

Factor V Leiden (Arg506Gln), a confounding genetic risk factor but not mandatory for the occurrence of venous thromboembolism in homozygotes and obligate heterozygotes for cystathionine beta-synthase deficiency.

Thrombosis is the major cause of morbidity and mortality in individuals with untreated classical homocystinuria (HCU) due to cystathionine beta-synthase deficiency and characterised by severe hyperhomocysteinaemia. In addition, mild and moderate hyperhomocysteinaemia and Factor V Leiden (FVL; Arg506Gln) have recently been identified as thrombotic risk factors. FVL. which renders resistance to activated Protein C, is the most common inherited genetic risk factor for thrombosis with a high allelic frequency amongst Caucasians. As thrombophilia is a multigenic disorder, 26 individuals with HCU (median age 17.6 years, range 3.5-32.8 years) and 36 obligate heterozygotes (median age 51.5 years, range 34-74 years) were screened for FVL. All the HCU individuals received treatment, except one, within 6 weeks of birth for those who were diagnosed at birth through the national newborn screening programme (n = 20) and at the time of diagnosis for those late detected (n = 5, mean age of starting treatment 4.9 years, range 1.4-11 years). All had been free from venous thrombosis, except one HCU individual and one HCU obligate heterozygote. Neither of the two individuals with venous thrombosis carried FVL. Two independent individuals with HCU (male 14.8 years; female 18.2 years) were heterozygous for FVL (allelic frequency 3.8%) and three independent HCU obligate heterozygotes (males 40 and 45.8 years; female 45.6 years) were also heterozygous for FVL (allelic frequency 4.16%). The findings in this small group suggest that FVL is not a mandatory but a significant confounding risk factor for the occurrence of thrombosis in HCU individuals and additional contributing factors may be required for thrombosis to occur in HCU obligate heterozygotes with FVL heterozygosity. Our data also suggest that treatment of HCU not only reduces the thrombotic risk in patients with isolated HCU but also in those with the additional FVL heterozygosity.

Adolescent↗
PubMed1998

Pediatric umbilical problems.

After birth, the normal umbilicus is a relatively simple structure. During the development of the embryo, however, this region is highly complex. Vestigial of the umbilical cord can be responsible for umbilical inflammation and drainage. This article reviews the embryology of the umbilicus and discusses a number of clinical problems seen in this area. The authors' aim is to aid the primary care pediatrician in evaluating, treating, and appropriately referring umbilical problems encountered in office practice.

Female↗
PubMed1998

Switching HMO providers. Dissatisfaction with emergency access cited as the primary reason for disenrollment.

The reasons consumers choose one service provider over another are not necessarily the same as the reasons for changing service providers. The distinctions may be even more important when the service in question is health care, specifically the decision to reenroll or switch HMO providers. The authors undertook a consumer survey to gauge the importance of 41 variables in the decision process. Using logistic regression analysis, they concluded that variables associated with access to emergency care services had the greatest impact on decisions to switch. This is contrary to other studies, which have ranked emergency care access much lower, and additional research is recommended.

Choice Behavior↗
PubMed1997

Oxygenated intraluminal perfluorocarbon protects intestinal muscosa from ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury to the intestinal mucosa occurs in several commonly encountered clinical situations, such as necrotizing enterocolitis and nonocclusive mesenteric insufficiency. No clinically feasible technique is available for mucosal preservation during ischemia. The goal of this work was to determine whether the continuous intraluminal flow of oxygenated perfluorocarbon (PFC) could protect mucosal integrity and function in a rat model of intestinal I/R injury. Rats were subjected to ischemia by clipping the superior mesenteric artery (SMA) for 60 minutes. Reperfusion was achieved by release of the clip for 120 minutes. Animals were divided into 4 groups: Sham (laparotomy alone), I/R (I/R alone), I + PFC/R (PFC was administered during the ischemic interval only), I/R + PFC (PFC was delivered only during reperfusion). Tissue sections were examined blindly to assess mucosal integrity, and mucosal dissacharidase activities were measured to assess function. Oxygenated PFC, when administered during ischemia alone, ameliorated I/R-induced mucosal injury; however, when it was delivered during reperfusion alone, the mucosal injury worsened. When oxygenated PFC was administered throughout I/R, the degree of mucosal injury was similar to the I + PFC/R group, and dissacharidase activities were preserved when compared with the I/R group. Intraluminal perfusion of oxygenated PFC during ischemia preserves mucosal function and integrity, and may offer a new treatment modality for a variety of mesenteric ischemic disorders.

Animals↗
PubMed1993

Cardiorespiratory responses to exercise training in septuagenarian women.

Cardiorespiratory responses to a 12wk moderate exercise training program were examined in 30 sedentary elderly women (mean age = 73.6 +/- 0.7 yr). In addition, 12 highly conditioned (HC) older women (mean age = 72.5 +/- 1.8 yr; 11.2 +/- 1.2 yr training; 1.6 +/- 0.2 hr.d-1 aerobic activity) were tested at baseline for cross-sectional comparisons. The VO2max and VEmax of the HC subjects were 67% and 36% higher, respectively, (p < 0.001) than the combined sedentary subjects at baseline. Sedentary subjects were randomly assigned to a walking (WALK) or calisthenics control (CAL) group. The WALK group exercised 5 d.wk-1 for 30-40 min per session at 60.0 +/- 1.9% heart rate reserve while the CAL group engaged in mild musculoskeletal exercise. The WALK group demonstrated significant improvement in VO2max compared to CAL subjects at 12 wk (12.6% vs 2.2%, F = 5.74, p = 0.005). These data show that septuagenarian women demonstrate significant improvement in maximal cardiorespiratory fitness through moderate exercise training.

Aged↗
PubMed1993

Physical activity and serum lipids and lipoproteins in elderly women.

OBJECTIVE: The relationship between cardiorespiratory exercise and serum lipid and lipoprotein levels was studied in elderly women. DESIGN: Randomized controlled experimental design with a follow up of 12 weeks; cross-sectional comparison at baseline. SETTING: Community-living elders in university exercise facilities. PARTICIPANTS: Thirty-two apparently healthy, sedentary elderly Caucasian women, 67 to 85 years of age. Ten highly conditioned elderly women, 65 to 84 years of age, who were active in endurance competitions and had been training for 11.2 +/- 1.2 years, were recruited at baseline for cross-sectional comparisons. INTERVENTIONS: Sedentary subjects were randomized to either a walking or calisthenic group. Intervention groups exercised 30 to 40 minutes, 5 days a week for 12 weeks, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. MEASUREMENTS: Serum lipids and lipoproteins, maximal aerobic capacity (VO2 max), four skinfolds, and dietary intake at baseline and after 5 and 12 weeks. RESULTS: When the highly conditioned group and combined group of sedentary subjects were compared at baseline, serum high-density lipoprotein cholesterol (HDL-C; 1.61 +/- 0.14 vs 1.27 +/- 0.05 mmol/L, respectively; P = 0.048) and triglycerides (1.29 +/- 0.15 vs 2.00 +/- 0.15, respectively; P = 0.002), but not total serum cholesterol (5.72 +/- 0.36 vs 5.72 +/- 0.19 mmol/L, respectively) and low-density lipoprotein cholesterol (LDL-C; 3.62 +/- 0.36 vs 3.72 +/- 0.18 mmol/L, respectively), were significantly different. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6% but did not result in any change in body weight, energy intake, dietary quality, or any of the serum lipids or lipoproteins. CONCLUSION: Highly conditioned and lean elderly women, when compared with their sedentary counterparts, had higher HDL-C and lower triglycerides, but similar total serum cholesterol and LDL-C values. However, twelve weeks of moderate cardiorespiratory exercise were not associated with an improvement in serum lipid or lipoprotein profiles in previously sedentary elderly women.

Aged↗
PubMed1991

Inhibition of adenylate cyclase by p-bromophenacyl bromide.

p-Bromophenacyl bromide (BPB) is an alkylating agent which has been used in biochemical studies as an inhibitor of phospholipase A2 activity. We report here that BPB irreversibly inhibited adenylate cyclase activity stimulated by hormones, forskolin, GppNHp, NaF, and cholera toxin. The action of BPB in S49 lymphoma cell membranes (wild type and cyc-) indicates that it can inhibit adenylate cyclase function in the absence of Gs. In the presence of Gs, however, inhibition of adenylate cyclase by BPB was enhanced, suggesting that BPB may covalently modify the catalytic protein on a site involved in activated catalytic functioning or critical to its interaction with Gs and/or additionally on the alpha s protein.

Acetophenones↗
PubMed1991

Muscarinic receptor binding is inhibited by quinacrine.

Quinacrine altered the equilibrium binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to the muscarinic receptor in membranes from N18TG2 neuroblastoma cells. At 1 microM quinacrine, the apparent Kd for [3H]QNB binding was shifted from 48 to 210 pM without a decrease in the maximum binding. The competition binding profile of quinacrine indicates that it displaced [3H]QNB binding with an IC50 of 460 nM in a manner consistent with competitive inhibition. Quinacrine blocked the muscarinic inhibition of cyclic AMP accumulation by carbachol in cultured N18TG2 neuroblastoma cells without affecting arachidonic acid release or Gi coupling to the adenylate cyclase. The disruption of muscarinic receptor function by quinacrine may provide an explanation for its blockade of the muscarinic response in cells.

Binding, Competitive↗
PubMed1989

Production of platelet-derived growth factorlike protein(s) by a human carcinoma cell line.

Human adrenal carcinoma cells (SW-13) produce and secrete autocrine growth factors. We now report that these cells secrete a factor that is biologically related to platelet-derived growth factor (PDGF). Serum-free medium conditioned by SW-13 cells stimulated incorporation of tritiated thymidine into DNA by quiescent Balb/c 3T3 cells in the presence of platelet-poor plasma. The conditioned media also competed with 125I-labeled PDGF for binding to PDGF receptors on human fibroblasts. Hybridization studies identified mRNA transcripts for PDGF-2/sis chains in logarithmically growing SW-13 cells. These data suggest secretion of PDGF-like mitogens by SW-13 cells.

Adrenal Gland Neoplasms↗
PubMed1988

Megestrol acetate-induced differentiation of 3T3-L1 adipocytes in vitro.

We recently observed significant weight gain in patients with advanced breast cancer treated with high-dose megestrol acetate. However, the mechanisms of this effect are completely unknown. As the analysis of the action of steroids in vivo is complex, we chose to examine the effects of megestrol acetate on the differentiation of a preadipocyte clone (L1) of the Swiss 3T3 mouse fibroblast cell line. Addition of insulin, fetal bovine serum, dexamethasone, and methyl-isobutylxanthine to confluent 3T3-L1 cells induced adipocyte differentiation, as verified by morphologic studies and analysis of the activity of the enzyme glycerol-3-phosphate dehydrogenase (G-3-PD), a specific and sensitive indicator of lipocyte function. Substitution of megestrol acetate for dexamethasone also resulted in greatly increased lipocyte differentiation. Tumor necrosis factor (TNF) alpha blocked the adipocyte differentiation induced by the combination of insulin, dexamethasone, and methyl-isobutylxanthine. Addition of megestrol acetate failed to reverse the inhibitory effect of TNF. Thus, megestrol acetate, in vitro, is a potent inducer of lipocyte differentiation. Further studies on the regulation of adipocyte differentiation and function in this model system may be important to clarify megestrol acetate's mechanism of action.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Cloning and regulation of messenger RNA for mouse apolipoprotein E.

A cDNA clone for mouse apolipoprotein E has been identified from a mouse liver cDNA library by a combination of differential colony hybridization and hybrid selection-translation. The identity of the clone was unambiguously established by partial sequencing and comparison with human apolipoprotein E nucleotide and amino acid sequences. In conjunction with an in vitro translation assay for apolipoprotein E, the clone has been used to examine the relative levels of apolipoprotein E mRNA in various tissues of the mouse and the regulation of apolipoprotein E synthesis in response to a diet rich in saturated fat and cholesterol. In the tissues examined, the clone was found to hybridize to a polyadenylated RNA species of approximately 1400 nucleotides. Of the tissues involved in lipoprotein synthesis, liver is very rich (about 1% of total) in apolipoprotein E mRNA while intestine contains only trace amounts. Appreciable levels of active apolipoprotein E mRNA (up to 10% of that in liver) are also detected in peripheral tissues not associated with lipoprotein synthesis, including lung, kidney, spleen, and heart. Thus, extrahepatic apolipoprotein E synthesis may contribute significantly to the levels present in plasma, and a possible function in "reverse cholesterol transport" is considered. When mice were placed on a high lipid diet there was no discernible change in the level of apolipoprotein E mRNA in liver or intestine, although the level of the circulating protein increased about 3-fold. We conclude that in mice the effect of diet on apolipoprotein E levels in blood does not result from induction of mRNA in these tissues.

Amino Acid Sequence↗
PubMed1983

Genetic evidence that the multiple apolipoprotein A-1 isoforms are encoded by a common structural gene.

We have used a genetic structural variation of apolipoprotein A-I in mice to examine the origin of the multiple charge isoforms of the plasma protein. Apolipoprotein A-I translated in vitro from hepatic or enteric mRNA revealed that the genetic variation simultaneously alters the charge of the protein produced by both tissues. The variation also shifted the charge of the entire family of isoforms found in plasma or translated in vitro. These results indicate that the protein produced by different tissues as well as the multiple isoforms are all derived from a common structural gene by processing.

Animals↗