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Biomedical subjects

D Atkinson

Publications and source records attributed to D Atkinson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of temperature on anti-predator behaviour in the guppy, Poecilia reticulata.

Warmer environmental temperatures are likely to increase the frequency of predator-prey interactions in ectothermic animals, and therefore might be expected to influence anti-predator behaviour. In a first experiment, groups of recently fed guppies, placed in a novel environment, schooled significantly more closely at 26 degrees than at 22 degreesC. Changes in two of three measures of schooling tendency over time indicated that aggregation increased during the trial periods, probably as a result of increased familiarity within the experimental groups. In a second experiment, pairs of female guppies were tested at 22 degrees and 26 degreesC, with and without predation threat from a confined cichlid. From multifactor analysis of 18 behaviour types, temperature was shown to affect behavioural time budgets profoundly, particularly in the presence of the predator. At the higher temperature, a shift occurred from inactive anti-predator behaviours and minimal foraging activity towards active predator inspection-related behaviours and a much higher level of feeding. Guppies in the warmer water might have been physically able to school more closely as a result of faster swimming ability, or might have used temperature as a cue indicating higher potential predation risk, and aggregated accordingly. The use of temperature as a source of information about the biotic environment is discussed. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation.

Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell death. The purpose of this in vitro study was to determine the mechanism of neutrophil death. We hypothesized that NO hastened cell death by inducing apoptosis. To mimic the clinical environment of patients with respiratory failure, we also studied the effects of hyperoxia on neutrophil cell viability and apoptosis. Isolated human neutrophils were exposed to 80% O2 (O2), NO at 20 ppm in room air (NO/RA), 20 ppm NO blended with 80% O2 (NO/O2), or RA alone (control) for 2 to 24 h. Experiments were repeated with NO concentrations of 5 and 50 ppm and with 20 ppm in the presence of superoxide dismutase (SOD). Neutrophils were also incubated in the absence or presence of neutrophil stimulant fMLP (10 nM). Neutrophil cell viability was measured by fluorescence viability/cytotoxicity assay. Neutrophil apoptosis was assessed by cell death detection ELISA for histone-associated DNA fragments, TdT transferase-mediated fluorescence-labeled dUTP nick end labeling (TUNEL) assay, and DNA fragmentation gel electrophoresis. NO/O2-exposed neutrophils showed decreased viability at 2 h (31.7 +/- 3.7%, mean % viability +/- SD) compared with control (94.7 +/- 4.7%), O2 (75.6 +/- 9.3%), and NO/RA (62.8 +/- 14.9%; P < 0.05 by ANOVA; n = 9). Although control neutrophils demonstrated marked apoptosis at 24 h, there was no significant apoptosis at 2, 4, or 6 h (P < 0.001 by Kruskal-Wallis, n = 20) as assessed by ELISA and TUNEL assays. When compared with RA controls at 2 h, neutrophils exposed to NO/O2 showed significantly more apoptosis (292% of control, range: 106 to 2,488%, P < 0.001 by ANOVA and Kruskal-Wallis) but not with exposure to NO/RA or O2 alone. These findings were confirmed by TUNEL assay (n = 4, P < 0.05). NO/ RA and NO/O2-exposed neutrophils demonstrated both evidence of necrosis and enhanced DNA fragmentation at 2 h by gel electrophoresis (n = 2). Fifty parts per million NO produced similar findings, but exposure to 5 ppm NO did not induce significant DNA fragmentation. Coincubation with SOD inhibited NO/ O2-associated apoptosis, suggesting peroxynitrite contributed to cell death. Stimulation with fMLP did not alter apoptosis induced in neutrophils exposed to NO/RA or NO/O2. We conclude that exogenous NO gas, at clinically relevant concentrations under hyperoxic conditions, induces cell death in neutrophils in part by enhancing DNA fragmentation.

Apoptosis↗
PubMed1997

Automatic correction of motion artifacts in magnetic resonance images using an entropy focus criterion.

We present the use of an entropy focus criterion to enable automatic focusing of motion corrupted magnetic resonance images. We demonstrate the principle using illustrative examples from cooperative volunteers. Our technique can determine unknown patient motion or use knowledge of motion from other measures as a starting estimate. The motion estimate is used to compensate the acquired data and is iteratively refined using the image entropy. Entropy focuses the whole image principally by favoring the removal of motion induced ghosts and blurring from otherwise dark regions of the image. Using only the image data, and no special hardware or pulse sequences, we demonstrate correction for arbitrary rigid-body translational motion in the imaging plane and for a single rotation. Extension to three-dimensional (3-D) and more general motion should be possible. The algorithm is able to determine volunteer motion well. The mean absolute deviation between algorithm and navigator-echo-determined motion is comparable to the displacement step size used in the algorithm. Local deviations from the recorded motion or navigator-determined motion are explained and we indicate how enhanced focus criteria may be derived. In all cases we were able to compensate images for patient motion, reducing blurring and ghosting.

Artifacts↗
PubMed1996

Thermal unfolding of human high-density apolipoprotein A-1: implications for a lipid-free molten globular state.

Apolipoprotein A-1 (apoA-1) in complex with high-density lipoprotein is critically involved in the transport and metabolism of cholesterol and in the pathogenesis of atherosclerosis. We reexamined the thermal unfolding of lipid-free apoA-1 in low-salt solution at pH approximately 7, by using differential scanning calorimetry and circular dichroism. At protein concentrations <5 mg/ml, thermal unfolding of apoA-1 is resolved as an extended peak (25 degrees C-90 degrees C) that can be largely accounted for by a single reversible non-two-state transition with midpoint Tm 57 +/- 1 degree C, calorimetric enthalpy deltaH(Tm)= 200 +/- 20 kcal/mol (1 kcal = 4.18 kJ), van't Hoff enthalpy deltaHv(Tm) approximately 32.5 kcal/mol, and cooperativity deltaHv(Tm)/deltaH(Tm) approximately 0.16. The enthalpy deltaH(Tm) can be accounted for by melting of the alpha-helical structure that is inferred by CD to constitute approximately 60% of apoA-1 amino acids. Farand near-UV CD spectra reveal noncoincident melting of the secondary and tertiary structural elements and indicate a well-defined secondary structure but a largely melted tertiary structure for apoA-1 at approximately 37 degrees C and pH 7. This suggests a molten globular-like state for lipid-free apoA-1 under near-physiological conditions. Our results suggest that in vivo lipid binding by apoA-1 may be mediated via the molten globular apolipoprotein state in plasma.

Apolipoprotein A-I↗
PubMed1996

High- and low-temperature unfolding of human high-density apolipoprotein A-2.

Human plasma apolipoprotein A-2 (apoA-2) is the second major protein of the high-density lipoproteins that mediate the transport and metabolism of cholesterol. Using CD spectroscopy and differential scanning calorimetry, we demonstrate that the structure of lipid-free apoA-2 in neutral low-salt solutions is most stable at approximately 25 degrees C and unfolds reversibly both upon heating and cooling from 25 degrees C. High-temperature unfolding of apoA-2, monitored by far-UV CD, extends from 25-85 degrees C with midpoint Th = 56 +/- 2 degrees C and vant Hoff's enthalpy delta H(Th) = 17 +/- 2 kcal/mol that is substantially lower than the expected enthalpy of melting of the alpha-helical structure. This suggests low-cooperativity apoA-2 unfolding. The apparent free energy of apoA-2 stabilization inferred from the CD analysis of the thermal unfolding, delta G(app)(25 degrees) = 0.82 +/- 0.15 kcal/mol, agrees with the value determined from chemical denaturation. Enhanced low-temperature stability of apoA-2 observed upon increase in Na2HPO4 concentration from 0.3 mM to 50 mM or addition of 10% glycerol may be linked to reduced water activity. The close proximity of the heat and cold unfolding transitions, that is consistent with low delta G(app)(25 degrees), indicates that lipid-free apoA-2 has a substantial hydrophobic core but is only marginally stable under near-physiological solvent conditions. This suggests that in vivo apoA-2 transfer is unlikely to proceed via the lipid-free state. Low delta H(Th) and low apparent delta Cp approximately 0.52 kcal/mol.K inferred from the far-UV CD analysis of apoA-2 unfolding, and absence of tertiary packing interactions involving Tyr groups suggested by near-UV CD, are consistent with a molten globular-like state of lipid-free apoA-2.

Apolipoprotein A-II↗
PubMed1996

MR imaging of surgical complications of systemic-to-pulmonary artery shunts.

Patients with a systemic-to-pulmonary artery shunt and positive findings on traditional imaging modalities such as chest X-ray, echocardiography, or cardiac angiography often can benefit from additional noninvasive imaging with magnetic resonance imaging (MRI). Diagnostic dilemmas encountered include: pseudoaneurysms, contained fluid collection (seroma) surrounding a shunt, and stenosis of the shunt anastomoses. MRI studies using traditional cardiac-triggered spin-echo (SE) imaging and the newer breathhold MRI studies with k-space segmented gradient-recalled echo (GRE) imaging can greatly help resolve diagnostic dilemmas. By combining different MR imaging techniques it becomes possible to clearly distinguish between pseudoaneurysms and seroma, to exclude an active leak and to sometimes visualize the distal anastomosis with more precision than conventional angiography. MRI is often able to add information needed for clinical decision making prior to surgical repair.

Adolescent↗
PubMed1996

Fluid-attenuated inversion recovery (FLAIR) for assessment of cerebral infarction. Initial clinical experience in 50 patients.

BACKGROUND AND PURPOSE: Our aim was to evaluate fluid-attenuated inversion recovery (FLAIR) sequence in the diagnosis of cerebral infarction with MRI. METHODS: A retrospective review was undertaken of 50 consecutive MRI studies ordered for suspected cerebrovascular accident. All studies included FLAIR and rapid acquisition with relaxation enhancement (RARE) T2-weighted spin-echo sequences. The two sequences were compared independently by four observers at two different institutions. Detectability of lesions and image quality were scored. RESULTS: Overall, FLAIR sequences proved superior in 10 patients, detecting acute cortical infarcts missed with RARE spin-echo technique in five patients. In five additional patients, improved characterization of chronic infarction and improved detection of microangiopathic deep hemispheric changes were observed. One brain stem infarct was missed with the FLAIR sequence. CONCLUSIONS: FLAIR offers advantages in detection of acute infarcts affecting the cortical ribbon, is a useful, rapid adjunct to conventional T2-weighted spin-echo sequences, and has the potential to replace these in the future.

Artifacts↗
PubMed1996

Fluid-attenuated inversion recovery (FLAIR): clinical prospectus of current and future applications.

A relative weakness of the traditional spin-echo technique, and particularly of the newer "FAST" or "TURBO" spin-echo sequences, has been diminished conspicuousness of lesions affecting the peripheral cortical mantle or those located in the periventricular region. This is a consequence of partial volume effects and high cerebrospinal fluid (CSF) signal adjacent to pathologic regions. Fluid-attenuated inversion recovery (FLAIR) is a magnetic resonance imaging (MRI) sequence that produces strong T2 weighting, suppresses the CSF signal, and minimizes contrast between gray matter and white matter. This effect produces images with significantly increased lesion-to-background CSF contrast and enhances the visibility of lesions as well as their detectability, particularly in the peripheral subcortical and periventricular regions. Applications are evolving, though preliminary reports highlight the superiority of FLAIR in the evaluation of infarction, multiple sclerosis, metastatic disease, tuberous sclerosis, and, possibly, subarachnoid hemorrhage. Early reports also address the application of FLAIR to imaging of the spinal cord. Modified versions of FLAIR are currently being developed; these modifications will further shorten acquisition times and eliminate pulsation artifacts. FLAIR may ultimately supplant conventional spin-echo imaging in routine MR screening of the brain.

Brain Diseases↗
PubMed1995

Hepatic cryosurgery in treating colorectal metastases.

BACKGROUND: The purpose of this study was to determine the effectiveness of cryosurgery as an adjunct to resection in treating patients with hepatic metastases from colorectal adenocarcinoma. METHODS: Forty-seven patients with documented metastases limited to the liver from colorectal adenocarcinoma were treated with cryosurgery with or without resection from November 1987 to February 1992 and were followed until February 1994. Intraoperative ultrasound was used to map the lesions and place the cryoprobes. Each lesion was frozen to -196 degrees centigrade for 15 minutes, thawed for 10 minutes, and frozen again for 15 minutes. Follow-up computed tomographic scans were obtained before hospital discharge and 6 months and 1 year after cryosurgery. Carcinoembryonic antigen levels were obtained monthly. RESULTS: Thirty-one males and 16 females, with a median age of 63 years, were treated. The median hospital stay was 10 days, and follow-up ranged from 24 to 57 months, with a median follow-up of 26 months. The actual survival at 24 months was 62%. Eleven percent of these patients had no evidence of disease at a median follow-up of 30 months. Complications included myoglobinuria, coagulopathy, pleural effusions, and bile duct injuries. Two patients (4%) died because of multisystem organ failure with irreversible coagulopathies. CONCLUSIONS: Cryosurgical ablation increases the number of patients with liver metastases who potentially can become disease free. However, the effect on overall survival will require a longer follow-up period.

Adult↗
PubMed1995

SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome.

Long QT syndrome (LQT) is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. We previously mapped three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7q35-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene. Single strand conformation polymorphism and DNA sequence analyses reveal identical intragenic deletions of SCN5A in affected members of two unrelated LQT families. The deleted sequences reside in a region that is important for channel inactivation. These data suggest that mutations in SCN5A cause chromosome 3-linked LQT and indicate a likely cellular mechanism for this disorder.

Amino Acid Sequence↗
PubMed1995

Cryoelectron microscopy of low density lipoprotein in vitreous ice.

In this report, images of low density lipoprotein (LDL) in vitreous ice at approximately 30 A resolution are presented. These images show that LDL is a quasi-spherical particle, approximately 220-240 A in diameter, with a region of low density (lipid) surrounded by a ring (in projection) of high density believed to represent apolipoprotein B-100. This ring is seen to be composed of four or five (depending on view) large regions of high density material that may represent protein superdomains. Analysis of LDL images obtained at slightly higher magnification reveals that areas of somewhat lower density connect these regions, in some cases crossing the projectional interiors of the LDL particles. Preliminary image analysis of LDL covalently labeled at Cys3734 and Cys4190 with 1.4-nm Nanogold clusters demonstrates that this methodology will provide an important site-specific marker in studies designed to map the organization of apoB at the surface of LDL.

Centrifugation, Density Gradient↗
PubMed1995

Hepatic cryosurgery in the treatment of unresectable metastases.

The treatment of unresectable hepatic metastases has generally been limited to systemic or intra-arterial chemotherapy. Cryosurgery has the advantage of potentially ablating such unresectable tumours. From November 1987 to August 1994, 140 patients underwent 155 procedures using hepatic cryosurgery with and without resection for documented metastatic disease. Intra-operative ultrasound was used for monitoring the freezing zone. The tumours were frozen using liquid nitrogen cooled to -196 degrees C for 15 min. The median number of lesions treated was three. Median hospital stay was 10 days. The operative mortality was 4%. Complications included coagulopathy, hypothermia, myoglobinuria, pleural effusions, ATN and infection. The median survival for all patients was 22 months. Of those patients followed for more than 2 years, the median survival was 25 months. Of the 65 patients that are still alive, the median follow-up is 27 months.

Adolescent↗
PubMed1995

The development of integrated public health information systems: a statement by the Joint Council of Governmental Public Health Agencies.

To truly enjoy the benefits of the information age, public health agencies at each level of government must work together to plan and implement integrated information systems that meet the needs of our dynamic profession. The Joint Council of Governmental Public Health Agencies, comprised of state and local health officials, has worked to identify the solutions to public health's information needs. Investments in integrated systems that support service delivery to clients will improve program management and enhance accountability for public funds. The ability to produce good, client-centered data will be essential as the nation's health and welfare systems change.

Data Collection↗
PubMed1994

Polymerase chain reaction heteroduplex polymorphism analysis by entangled solution capillary electrophoresis.

Heteroduplex DNA polymorphism analysis (HPA) makes use of conformational polymorphisms to alter electrophoretic mobility of fragments and can be used to detect non-restrictable loci. We have developed a novel application of entangled solution capillary electrophoresis (ESCE) to separate heteroduplex and homoduplex DNA molecules. The addition of ethidium bromide and glycerol to the free solution sieving buffer resulted in the improved peak resolution and good reproducibility. Reannealed polymerase chain reaction products could be used directly for mutation screening and with fully automated ESCE the entire HPA may be completed in less than 30 min including sample handling. This technology could provide a rapid and highly efficient way for screening rare mutations among large numbers of individuals.

Base Sequence↗
PubMed1994

Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity.

Cardiac arrhythmias cause sudden death in 300,000 United States citizens every year. In this study, we describe two new loci for an inherited cardiac arrhythmia, long QT syndrome (LQT). In 1991 we reported linkage of LQT to chromosome 11p15.5. In this study we demonstrate further linkage to D7S483 in nine families with a combined lod score of 19.41 and to D3S1100 in three families with a combined score of 6.72. These findings localize major LQT genes to chromosomes 7q35-36 and 3p21-24, respectively. Linkage to any known locus was excluded in three families indicating that additional heterogeneity exists. Proteins encoded by different LQT genes may interact to modulate cardiac repolarization and arrhythmia risk.

Base Sequence↗
PubMed1994

Improved MR angiography: magnetization transfer suppression with variable flip angle excitation and increased resolution.

Results at conventional magnetic resonance (MR) angiography were compared with results at MR imaging with a sequence combining optimized magnetization transfer (MT) saturation and tilted optimized nonsaturating excitation (TONE). Forty images were obtained of five healthy volunteers and five patients with known intracranial vascular abnormalities (four men and six women, aged 22-72 years). Four blinded readers found improved vessel penetration, enhanced vessel-to-background contrast, the better vessel detail in the MT saturation-TONE images than in the conventional three-dimensional time-of-flight MR angiograms.

Adult↗
PubMed1994

Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene.

Supravalvular aortic stenosis (SVAS) is an inherited vascular disease that can cause heart failure and death. SVAS can be inherited as an autosomal dominant trait or as part of a developmental disorder, Williams syndrome (WS). In recent studies we presented evidence suggesting that a translocation disrupting the elastin gene caused SVAS in one family while deletions involving the entire elastin locus caused WS. In this study, pulsed-field, PCR, and Southern analyses showed that a 100-kb deletion of the 3' end of the elastin gene cosegregated with the disease in another SVAS family. DNA sequence analysis localized the breakpoint between elastin exons 27 and 28, the same region disrupted by the SVAS-associated translocation. These data indicate that mutations in the elastin gene cause SVAS and suggest that elastin exons 28-36 may encode critical domains for vascular development.

Aortic Stenosis, Subvalvular↗