Biomedical subjects

J A Noble

Publications and source records attributed to J A Noble.

At least 19 recordsLinked to original sources

PubMed2005

D6S26515 marks a DRB115, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk. METHODS: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden. RESULTS: We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15-=0.017 (95% CI 0.005, 0.062), p<0.001]. CONCLUSIONS/INTERPRETATION: Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.

Adult↗

PubMed2005

Extended DR3-D6S273-HLA-B haplotypes are associated with increased susceptibility to type 1 diabetes in US Caucasians.

Human leukocyte antigen (HLA)-DR3 haplotypes are associated with susceptibility to type 1 diabetes (T1D). Reports from Northern European populations show that an allele (D6S273*2) at a microsatellite mapping to HLA class III marks an extended DR3-B18 haplotype associated with increased susceptibility to T1D. Consistent with previous reports, D6S273*2 marked a highly predisposing DR3 haplotype in European origin, multiplex families from the USA. Furthermore, we observed on DR3 haplotypes that other D6S273 alleles were also significantly associated with both increased transmission (D6S273*5; P < 0.02) and decreased transmission (D6S273*7; P < 0.05) to affected individuals. The differential transmission was most evident among DR3-B8 haplotypes. Neither HLA-B*1801 nor any alleles of D6S273 were associated with increased T1D predisposition on DR4 haplotypes. These data indicate that multiple alleles of D6S273 mark a susceptibility locus whose effect we were able to detect only among DR3 haplotypes but not limited to DR3-B18 haplotypes.

Diabetes Mellitus, Type 1↗

PubMed2004

Measurement of the speed of sound in follicular fluid.

BACKGROUND: Measurement of ovarian follicles by ultrasound is common practice in fertility treatment. However, the effect of the speed of sound is not taken into account. We present results from a study aimed at measuring this. METHODS: The speed of sound was measured in samples of follicular fluid aspirated from patients undergoing fertility treatment. The transmitted and received pulses from a single element ultrasound transducer were recorded using a digital oscilloscope for a pulse passed through a sample of the fluid. The distance over which the pulse travelled was known from calibration with pure water. Variation with temperature was investigated in the range 25-45 degrees C. Dependence on ultrasound frequency, patient and time from aspiration were also investigated. RESULTS: The speed of sound in follicular fluid was found to be 1550+/-3 m/s at 37.3 degrees C using 5.0 MHz ultrasound. The speed varied from 1528+/-3 m/s at 24.8 degrees C to 1561+/-3 m/s at 44.8 degrees C. Variation with patient, time and frequency were not detected. CONCLUSION: The speed of sound in follicular fluid at body temperature is 1550 m/s. This small difference from the speed assumed by the ultrasound machine corresponds to the systematic bias in volume measurement evident in previously published results.

Biopsy, Needle↗

PubMed2004

Assessment of a technique for 2D-3D registration of cerebral intra-arterial angiography.

This study assesses the ability of a computer algorithm to perform automated 2D-3D registrations of digitally subtracted cerebral angiograms. The technique was tested on clinical studies of five patients with intracranial aneurysms. The automated procedure was compared against a gold standard manual registration, and achieved a mean registration accuracy of 1.3 mm (SD 0.6 mm). Two registration strategies were tested using coarse (128 x 128 pixel) or fine (256 x 256 pixel) images. The mean registration errors proved similar but registration of the lower resolution images was 3 times quicker (mean registration times 33 s, SD 13 s for low and 150 s SD 48 s for high resolution images). The automated techniques were considerably faster than manual registrations but achieved similar accuracy. The technique has several potential uses but is particularly applicable to endovascular treatment techniques.

Algorithms↗

PubMed2001

Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1.

In this report, we present evidence that the HLA class II DPB1 locus (or a locus with alleles in linkage disequilibrium with DPB1) contributes to Type I diabetes (IDDM) susceptibility in addition to the contribution of the HLA DR and DQ loci. The marker association segregation chi-square (MASC) method, which fits both genotype frequency and affected sib-pair identity-by-descent (IBD) distributions, was applied to 257 sib pairs affected with IDDM. Fitting DR-DQ as the sole HLA susceptibility loci was strongly rejected. Next, we considered the DPB1 contribution to disease susceptibility. Published reports indicate a predisposing role for alleles DPB1*0301 and DPB1*0202, including our previous stratification analyses of association data on this sample. IDDM probands were stratified into those not carrying the alleles DPB1*0301 and DPB1*0202 (group DPB1-A), and those carrying at least one copy of either allele (group DPB1-B). Both groups of probands have almost identical frequencies of DR and DQ haplotypes but significantly different IBD distributions in the subset of families with probands who do not carry the highly predisposing DR3/DR4 genotype. In these data, DPB1 (or a locus in linkage disequilibrium), in addition to DR-DQ, is involved in IDDM susceptibility and affects IBD in the HLA region. Addition of DPB1 in a genetic model of IDDM gives a better fit to the data than consideration of DR-DQ alone. Our results are consistent with previous reports implicating DPB1 in IDDM susceptibility.

Alleles↗

PubMed2001

Quantitative regional analysis of myocardial wall motion.

This paper presents a new technique for semiautomatic quantification of regional heart function from 2-D echocardiography. It uses a novel left ventricular border tracking algorithm based on shape-space ideas that we have recently described. In this paper, we show how to decompose the tracked output into clinically meaningful segmental parameters (wall excursion and thickening), using what we call a computational interpretational space (CIS). This leads to a quantitative and automatic scoring scheme for endocardial excursion and myocardial thickening. The method is illustrated on data from a patient with a myocardial infarct in the apical anterior/inferior region of the heart and is also assessed in a small retrospective dobutamine stress echocardiography clinical case study.

Algorithms↗

PubMed2001

Enhancement of contrast regions in suboptimal ultrasound images with application to echocardiography.

In this paper we propose a novel feature-based contrast enhancement approach to enhance the quality of noisy ultrasound (US) images. Our approach uses a phase-based feature detection algorithm, followed by sparse surface interpolation and subsequent nonlinear postprocessing. We first exploited the intensity-invariant property of phase-based acoustic feature detection to select a set of relevant image features in the data. Then, an approximation to the low-frequency components of the sparse set of selected features was obtained using a fast surface interpolation algorithm. Finally, a nonlinear postprocessing step was applied. Results of applying the method to echocardiographic sequences (2-D + T) are presented. The results demonstrate that the method can successfully enhance the intensity of the interesting features in the image. Better balanced contrasted images are obtained, which is important and useful both for manual processing and assessment by a clinician, and for computer analysis of the sequence. An evaluation protocol is proposed in the case of echocardiographic data and quantitative results are presented. We show that the correction is consistent over time and does not introduce any temporal artefacts.

Acoustics↗

PubMed2001

Respiratory motion compensation for 3-D freehand echocardiography.

Motion of the diaphragm during respiration causes a displacement of the heart relative to the position of a transthoracic ultrasound (US) probe. These respiration-induced shifts of cardiac position can lead to spatial misalignments of data when reconstructed in 3-D. We show how to compensate for this motion using a technique that extends the tracking of the probe to additionally monitor a marker placed on the patient umbilicus. The motion of the umbilicus is calibrated to that of the diaphragm using one additional scan. This calibration is used to correct the 3-D spatial positions of cardiac images acquired from multiple acoustic views. At both systole and diastole, segmentations of the endocardial border visually appear more consistent after our correction than with no correction. Long and short axis segmentations should intersect on the endocardium. After correction, their separation at the closest point is shown to be reduced.

Calibration↗

PubMed2001

Transracial evidence for the influence of the homologous HLA DR-DQ haplotype on transmission of HLA DR4 haplotypes to diabetic children.

The HLA-DQB1*0302 allele on DR4 haplotypes is a marker for type 1 diabetes susceptibility and it is an especially high-risk allele in DR3/4 because of its preferential distribution in Caucasian DR3/4 patients. In Asians, not only DQB1*0302 but also DQB1*0401 on DR4 haplotypes are associated with type 1 diabetes. We investigated whether the contribution of these DQ molecules was also genotype-dependent in Asians. Although the prevalence of the DR4-DQB1*0302 haplotype did not differ in patients vs. controls, the DR3/4-DQB1*0302 genotype had a RR of 12 (P<10(-4)). Moreover, a significant association of DQB1*0302 with the DR3/4 genotype was found (RR=3, P<10(-2)). In contrast, the distribution of DQB1*0401 alleles of DR4/X (X: other than 3, 4) is different from that of DR3/4 and DR4/4. Especially a significant association of DQB1*0401 with DR4/X (X: other than 1, 3, 4) was found (RR=3, P<10(-3)). The frequency of transmission of the DR4-DQB1*0302 haplotypes to diabetic offspring with DR3 was 80%, while to those without DR3 was 40%. In contrast, the transmission of the DR4-DQB1*0401 to those with DR3 was 60%, while to those without DR3 was 80%. High-risk DR4 subtypes were predominant in DR4/X (RR=7, P<10(-3)), whereas protective DR4 subtypes were observed mainly in the DR3/4 (RR=3, P<0.05). The association with diabetes and transmission to a diabetic offspring of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. This might contribute not only to the synergistic effect of DR3/4, but also to the susceptibility influence of HLA DQB1*0401 alleles confined to DR4/X.

Asian People↗

PubMed2000

2D+T acoustic boundary detection in echocardiography.

In this paper we address the problem of spatio-temporal acoustic boundary detection in echocardiography. We propose a phase-based feature detection method to be used as the front end to higher-level 2D+T/3D+T reconstruction algorithms. We develop a 2D+T version of this algorithm and illustrate its performance on some typical echocardiogram sequences. We show how our temporal-based algorithm helps to reduce the number of spurious feature responses due to speckle and provides feature velocity estimates. Further, our approach is intensity-amplitude invariant. This makes it particularly attractive for echocardiographic segmentation, where choosing a single global intensity-based edge threshold is problematic.

Acoustics↗

PubMed2000

Flow cytometry for determination of the efficacy of contact lens disinfecting solutions against Acanthamoeba spp.

Flow cytometric analyses of cellular staining with fluorescent viability dyes and direct microscopic observations of methylene blue exclusion were compared for evaluation of the effects of a chlorhexidine gluconate-based contact lens disinfectant solution and a polyhexamethylene biguanide solution against cysts and trophozoites of Acanthamoeba castellanii and Acanthamoeba polyphaga. The flow cytometric procedure with propidium iodide (used to stain dead cells) indicated that more than 90% of trophozoites of both species (inocula of 10(5) to 10(6)/ml) at 22 degrees C lost their viability after 4 h of exposure to chlorhexidine. When propidium iodide was used in combination with fluorescein diacetate (for live cells), the apparent number of propidium iodide-stained cells was reduced, but the relative efficacies of the two biguanide solutions appeared unchanged from those evident with the single dyes; the chlorhexidine solution was more effective than the polyhexamethylene biguanide solution. Similar data were obtained with the more cumbersome methylene blue exclusion procedure. Flow cytometric analyses provided a statistically reproducible and rapid procedure for determining the relative antiamoebal efficacies of the disinfecting solutions.

Acanthamoeba↗

PubMed2000

DR- and DQ-associated protection from type 1A diabetes: comparison of DRB11401 and DQA10102-DQB10602.

The transmission disequilibrium test was used to analyze haplotypes for association and linkage to diabetes within families from the Human Biological Data Interchange type 1 diabetes repository (n = 1371 subjects) and from the Norwegian Type 1 Diabetes Simplex Families study (n = 2441 subjects). DQA1*0102-DQB1*0602 was transmitted to 2 of 313 (0.6%) affected offspring (P < 0.001, vs. the expected 50% transmission). Protection was associated with the DQ alleles rather than DRB1*1501 in linkage disequilibrium with DQA1*0102-DQB1*0602: rare DRB1*1501 haplotypes without DQA1*0102-DQB1*0602 were transmitted to 5 of 11 affected offspring, whereas DQA1*0102-DQB1*0602 was transmitted to 2 of 313 affected offspring (P < 0.0001). Rare DQA1*0102-DQB1*0602 haplotypes without DRB1*1501 were never transmitted to affected offspring (n = 6). The DQA1*0101-DQB1*0503 haplotype was transmitted to 2 of 42 (4.8%) affected offspring (P < 0.001, vs. 50% expected transmission). Although DRB1*1401 is in linkage disequilibrium with DQB1*0503, neither of the two affected children who carried DQA1*0101-DQB1*0503 had DRB1*1401. However, all 13 nonaffected children who inherited DQA1*0101-DQB1*0503 had DRB1*1401. In a case-control comparison of patients from the Barbara Davis Center, DQA1*0101-DQB1*0503 was found in 5 of 110 (4.5%) controls compared with 3 of 728 (0.4%) patients (P < 0.005). Of the three patients with DQB1*0503, only one had DRB1*1401. Our data suggest that both DR and DQ molecules (the DRB1*1401 and DQA1*0102-DQB1*0602 alleles) can provide protection from type 1A diabetes.

Cell Line↗

PubMed2000

Common susceptibility and transmission pattern of human leukocyte antigen DRB1-DQB1 haplotypes to Korean and Caucasian patients with type 1 diabetes.

The incidence of type 1 diabetes in Korea is less than 1/10th of that in the United States, and it has been suggested that human leukocyte antigen (HLA) alleles of Asian patients associated with diabetes differ from those of Caucasians. In this study we analyzed the common susceptibility and transmission pattern of a series of HLA DRB1-DQB1 haplotypes to Korean and Caucasian patients with type 1 diabetes. We performed HLA DR and DQ typing of 158 type 1 diabetic patients in a case control study, 140 nondiabetic subjects from the same geographical area, 49 simplex families from Seoul, and 283 families from the Human Biological Data Interchange. Although the haplotype frequencies in the two populations are quite different, when identical haplotypes are compared, their odds ratios are nearly the same. For all parental haplotypes, the transmission to diabetic offspring was similar for Korean and Caucasian families (r = 0.8; P: < 10(-)(4)). Allowing for ethnic differences in allelic associations due to different frequencies of DRB1 and DQB1 haplotypes (linkage disequilibrium), these data show, not only by case-control comparison but also by transmission analyses of the haplotypes, that the susceptibility effects of DRB1-DQB1 haplotypes are consistent in Koreans and Caucasians. Thus, the influence of class II susceptibility and resistance alleles appears to transcend ethnic and geographic diversity of type 1 diabetes.

Adolescent↗

PubMed2000

The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes.

HLA-DPB1 genotypes were determined for samples from 269 multiplex Caucasian families from the Human Biological Data Interchange. DRB1 and DQB1 loci were also characterized, allowing assignment of DPB1 alleles to haplotypes and calculation of linkage disequilibrium values. Frequencies for several DPB1 alleles differed significantly between patients and affected family-based control subjects. Some differences were attributable to linkage disequilibrium with DR and DQ alleles, whereas others were not. DPB1*0301 and DPB1*0202 alleles are predisposing for type 1 diabetes in these data, not only in analyses of individual alleles, but also in genotype analyses. DPB1*0402 appears protective; however, stratification analysis indicates that its protective effect is specific for DR3 haplotypes. A protective role for DPB1*0401 is suggested by genotype analysis. For increased statistical power, DPB1 alleles were pooled into three categories: susceptible, neutral, and protective after removal of effects due to linkage disequilibrium with DR-DQ. Analysis of these pools suggests that DPB1 primarily affects susceptibility to, rather than protection from, type 1 diabetes in a dominant fashion. This effect is more apparent in patients with genotypes other than the highest risk DR3/DR4-DQB1*0302 genotype. These data support a role for the DPB1 locus in conferring susceptibility to type 1 diabetes.

Alleles↗

PubMed1999

Determination of glutamic acid decarboxylase 65 peptides presented by the type I diabetes-associated HLA-DQ8 class II molecule identifies an immunogenic peptide motif.

Particular HLA class II allelic sequences are associated with susceptibility to type I diabetes. To understand the mechanism, knowledge of the molecular nature of the specific TCR/peptide/class II interactions involved in the disease process is required. To this end, we have introduced the diabetes-associated human class II HLA-DQ8 allele (DQA1*0301/DQB1*0302) as a transgene into mice and analyzed T cell responses restricted by this molecule to an important Ag in human diabetes, human glutamic acid decarboxylase 65. Hybridomas were used to determine the particular peptides from this Ag presented by HLA-DQ8 to T cells and to map the core minimal epitopes required for T cell stimulation. Analysis of these core epitopes reveals a motif and relevant features for peptides that are immunogenic to T cells when presented by HLA-DQ8. The major immunogenic epitopes of glutamic acid decarboxylase 65 do not contain a negatively charged residue that binds in the P9 pocket of the HLA-DQ8 molecule. PBMC from HLA-DQ8+ diabetic and nondiabetic individuals respond to these peptides, confirming that the mouse model is a useful tool to define epitopes of autoantigens that are processed by human APC and recognized by human T cells.

Animals↗

PubMed1999

Evaluating a robust contour tracker on echocardiographic sequences.

In this paper we present an evaluation of a robust visual image tracker on echocardiographic image sequences. We show how the tracking framework can be customized to define an appropriate shape space that describes heart shape deformations that can be learnt from a training data set. We also investigate energy-based temporal boundary enhancement methods to improve image feature measurement. Results are presented demonstrating real-time tracking on real normal heart motion data sequences and abnormal synthesized and real heart motion data sequences. We conclude by discussing some of our current research efforts.

Algorithms↗

PubMed1999

An adaptive segmentation algorithm for time-of-flight MRA data.

A three-dimensional (3-D) representation of cerebral vessel morphology is essential for neuroradiologists treating cerebral aneurysms. However, current imaging techniques cannot provide such a representation. Slices of MR angiography (MRA) data can only give two-dimensional (2-D) descriptions and ambiguities of aneurysm position and size arising in X-ray projection images can often be intractable. To overcome these problems, we have established a new automatic statistically based algorithm for extracting the 3-D vessel information from time-of-flight (TOF) MRA data. We introduce distributions for the data, motivated by a physical model of blood flow, that are used in a modified version of the expectation maximization (EM) algorithm. The estimated model parameters are then used to classify statistically the voxels into vessel or other brain tissue classes. The algorithm is adaptive because the model fitting is performed recursively so that classifications are made on local subvolumes of data. We present results from applying our algorithm to several real data sets that contain both artery and aneurysm structures of various sizes.

Algorithms↗

PubMed1999

Determining x-ray projections for coil treatments of intracranial aneurysms.

The endovascular coil embolization of intracranial saccular aneurysms requires a set of specific X-ray images with which to view the aneurysm during coiling. These two-dimensional (2-D) images, known as working projections, should be optimal for measuring the aneurysm sac diameter, inserting the first coil, and checking coil overhang into the surrounding vessels. At present the gantry tilt that produces these images is found by the radiologist by trial and error. In this paper, we present a method for automatically finding the angles that will produce the desired X-ray projections. Our method consists of four steps: 1) finding the location and orientation of the aneurysm neck; (2) labeling the aneurysm sac; 3) determining the optimal tilts for viewing the aneurysm during coiling; and 4) adjusting the optimal tilts for change in the patient orientation between pre-Guglielmi detachable coil (GDC) scanning and the coiling treatment. We discuss these steps and present results of the algorithm applied to pathological examples in the form of simulated X-ray images. A final discussion is given for one example where our results have been applied in a clinical situation.

Algorithms↗