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Biomedical subjects

D Nickerson

Publications and source records attributed to D Nickerson.

13 recordsLinked to original sources

Automated Talairach atlas labels for functional brain mapping.

An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced [Lancaster et al., 1997]. In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of activation coordinates from over 250 published functional brain-mapping studies and with manual atlas-derived labels from an expert group using a subset of these activation coordinates. Automated labeling by the TD system compared well with authors' labels, with a 70% or greater label match averaged over all locations. Author-label matching improved to greater than 90% within a search range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search utility was evaluated using individual activations from the M1 mouth region (30 subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4 & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the TD system's overall match with authors' labels (90%) was better than that of the expert group (80%). When used in concert with authors' deeper knowledge of an experiment, the TD system provides consistent and comprehensive labels for brain activation foci. Additional suggested applications of the TD system include interactive labeling, anatomical grouping of activation foci, lesion-deficit analysis, and neuroanatomy education.

Anatomy, Artistic↗

An improved procedure for the preparation of X-ray diffraction-quality crystals of cytochrome p450cam.

A procedure for the crystallization of recombinant cytochrome P450cam has been developed which avoids the difficulties inherent in the glass-capillary free-interface diffusion method reported previously. The surface mutation, Cys334-->Ala (C334A), originally designed to prevent dimer formation and thus improve routine handling of the enzyme, facilitates crystallization by the hanging-drop vapour-diffusion technique. Crystals of (C334A)P450cam grow within 48 h and diffract to beyond 1.2 A at 100 K in-house on a Siemens multiwire area detector. Data have been collected from the camphor-bound form to 1.35 A.

Alanine↗

k-tree method for high-speed spatial normalization.

The general approach to spatial normalization using a deformation field is presented. Current high degree-of-freedom deformation methods are extremely time-consuming (10-40 hr), and a k-tree method is proposed to greatly reduce this time. A general k-tree method for analysis of source and target images and synthesis of deformation fields is described. The k-tree method simplifies scale control and feature extraction and matching, making it highly efficient. A two-dimensional (2-D), or quadtree, application program was developed for preliminary testing. The k-tree method was evaluated with 2-D images to test rotating ability, nonhomologous region matching, inner and outer brain-structure independence, and feasibility with human brain images. The results of these tests indicate that a three-dimensional (3-D), or octree, method is feasible. Preliminary work with an octree application program indicates that a processing time of under 10 min for 256(3) image arrays is attainable on a Sun Ultra30 workstation.

Algorithms↗

Polymorphism detection and sequence analysis of human T-cell receptor V alpha-chain-encoding gene segments.

The T-cell receptor (Tcr) provides specificity for antigen recognition by its variable domain, primarily consisting of two germline encoded variable (V) region gene segments. Thus it has been suggested that inherited polymorphisms in the TCRV gene segments could contribute to differential immune responsiveness (e.g., autoimmunity) in human populations. In the present study, we have sought potentially functional polymorphisms in the germline TCRAV gene segments. Using denaturing gradient gel electrophoresis on polymerase chain reaction (PCR)-amplified products from the pooled DNA of many individuals, we identified polymorphisms in the TCRAV2S1, AV4S1, AV7S1, and AV8S1 gene segments. A complete DNA sequence analysis of these PCR products identified polymorphisms that affected amino acids in the predicted antigen-binding regions of the Tcr alpha chain, as well as polymorphisms in the introns. Genotype analysis of all nine DNA point mutations showed a 5%-50% range (averaging 35%) of minor allele frequencies, often resulting in individuals homozygous for the alternate allele forms. All possible haplotype combinations of the amino acid-affecting polymorphisms were found, indicating that in human populations there are a large number of different germline haplotypes encoding V gene segment alleles. These TCRAV coding region polymorphisms provide the rationale for, and allow the direct testing of, hypotheses concerning inherited polymorphisms within the T-cell receptor genes that may contribute to autoimmune susceptibility.

Base Sequence↗

Zygomatic fractures: comparison of methods of internal fixation.

We have analyzed different methods of internal fixation of simple displaced fractures of the zygoma in an attempt to define the simplest method(s) of achieving postreduction stability. Twenty-five combinations of interfragmentary wiring and miniplate and screw fixation of fractured zygomas on human skulls were compared for postreduction rotational stability against stresses simulating the muscular forces that act to displace the zygoma once it has been reduced. Analysis of the data suggests that while three-point fixation using either miniplates or interosseous wires allows for virtually no displacement, two-point fixation and in some cases one-point fixation provide acceptable stability. In general, stable fixation is achieved by methods that involve the use of at least one miniplate and incorporate the frontozygomatic suture line as one of the points of fixation.

Adolescent↗

Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice.

We evaluated the efficacy of pretreatment with phenytoin and phenobarbital to prevent seizures in mice given convulsive doses of theophylline. The control LD50 for theophylline was determined in 48 mice by intraperitoneal injections of increasing doses without anticonvulsant treatment. Anticonvulsant effects were determined in 105 additional mice pretreated with either phenytoin 30 mg/kg (n = 35), phenobarbital 35 mg/kg (n = 30), or phenobarbital 60 mg/kg (n = 40) one hour before theophylline administration. The theophylline LD50 (95% confidence interval) was 239 mg/kg (range, 229 to 248 mg/kg) for controls, 204 mg/kg (range, 194 to 214 mg/kg) for phenytoin, 305 mg/kg (range, 288 to 323 mg/kg) for low-dose phenobarbital, and 319 mg/kg (range, 307 to 331 mg/kg) for high-dose phenobarbital. Each LD50 differed significantly from control (P less than .05). The phenobarbital groups were significantly different from phenytoin (P less than .05) but not from each other. Theophylline serum concentrations were not significantly different among groups after adjustment for different doses. The mean +/- SEM time to seizure in minutes after adjustment for theophylline dose was 23.5 +/- 4.0 minutes for controls, 5.7 +/- 7.5 minutes for phenytoin, 44.1 +/- 7.1 minutes for low-dose phenobarbital, and 63.7 +/- 6.5 minutes for high-dose phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantifying changes in regional myocardial perfusion with aortic contrast echocardiography.

We developed a technique to assess regional myocardial perfusion by quantifying echocardiographic myocardial contrast appearance and intensity after aortic root injection of an agitated diatrizoate meglumine solution. The technique was validated by comparing digitized echocardiographic contrast parameters to regional perfusion in the circumflex bed determined by calibrated Doppler flow probe and antemortem monastral blue staining. Regional perfusion was altered by circumflex stenosis, occlusion, and reactive hyperemia. Contrast effects were measured in an initial subset of six dogs by peak intensity change, time to peak intensity, maximal rate of intensity rise, and mean intensity change integrated over 1, 2, or 3 seconds after contrast appearance (MI1, MI2, MI3). MI2 and MI3 best predicted regional perfusion (r = 0.93, standard error of the estimate [SEE] 0.38 ml/gm/min for each). These findings were confirmed in a second subset of six dogs (r = 0.84, SEE = 0.70 ml/gm/min). Although there was a relatively broad standard error for the prediction of absolute perfusion for the pooled data, for individual dogs data were internally consistent so that each had r greater than 0.88 for its varied flow states. The hyperemic ratio calculated by contrast echocardiography correlated well with the Doppler value (r = 0.85). Observer and study-to-study predictive variabilities were small (SEE 0.19 to 0.32 ml/gm/min). No alterations were seen in hemodynamics or reactive hyperemia after 25 consecutive injections over a 90-minute period. Contrast echocardiography with aortic root contrast injection tracks changes in regional blood flow. This approach can assess regional coronary reserve and detect changes in regional myocardial perfusion during acute ischemia and drug intervention.

Animals↗

Acute development of invasive squamous cell carcinoma in a split-thickness skin graft donor site.

Reports exist in the literature where metastasis or inadvertent operative spread has transferred excised squamous cell carcinoma, keratoacanthoma, and melanoma to skin graft donor sites. This report examines the potential for the reverse to occur. A de novo squamous cell carcinoma developing in a split-thickness skin graft donor site within 5 weeks of harvest for acute burn coverage is presented. As repeated harvesting from this site was performed, the transplantation of carcinoma could have occurred. The etiology of this squamous cell carcinoma, the risk of transplantation, and the 18-month follow-up are presented.

Acute Disease↗