PubMed Health⌕ Search

Biomedical subjects

K Young

Publications and source records attributed to K Young.

At least 19 recordsLinked to original sources
PubMed2006

Robust analysis of short echo time (1)H MRSI of human brain.

Short echo time proton MR Spectroscopic Imaging (MRSI) suffers from low signal-to-noise ratio (SNR), limiting accuracy to estimate metabolite intensities. A method to coherently sum spectra in a region of interest of the human brain by appropriate peak alignment was developed to yield a mean spectrum with increased SNR. Furthermore, principal component (PC) spectra were calculated to estimate the variance of the mean spectrum. The mean or alternatively the first PC (PC(1)) spectrum from the same region can be used for quantitation of peak areas of metabolites in the human brain at increased SNR. Monte Carlo simulations showed that both mean and PC(1) spectra were more accurate in estimating regional metabolite concentrations than solutions that regress individual spectra against the tissue compositions of MRSI voxels. Back-to-back MRSI studies on 10 healthy volunteers showed that mean spectra markedly improved reliability of brain metabolite measurements, most notably for myo-inositol, as compared to regression methods.

Adult↗
PubMed2006

Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging.

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain.

Algorithms↗
PubMed2006

The gross anatomy of the male reproductive system of a neotropical rodent: the agouti (Dasyprota leporina).

The literature available on the agouti (Dasyprocta leporina) is very limited. The agouti is a Neotropical rodent found in Trinidad and Tobago, Central and South America. This study focuses on one of the many unexplored areas relating to the species, the male reproductive system. The results showed that the mean testicular length, diameter and weight was 3.67 +/- 0.12 cm, 1.67 +/- 0.04 cm and 5.03 +/- 0.52 g respectively. The paired testes and epididymis were found in contact with the abdominal muscles within scrotal pouches, which are evaginations of the caudoventral abdominal wall. The caput epididymis is enclosed by a fat body. The ductus deferens has a mean length and diameter of 10.98 +/- 0.40 cm and 0.14 +/- 0.01 cm respectively. At the urethral end of the ductus deferens the diameter of each duct expends to form the ampulla. The mean diameter of each of the ampulla was 0.25 cm. The accessory sex organs of the male agouti (D. leporina) include the vesicular glands, the coagulating glands, the prostate glands and the bulbourethral glands. The penis of the agouti is U-shaped with a mean length of 9.90 +/- 0.43 cm. The glans penis contains an os penis, a pair of lateral penile cartilages and paired ventral keratinaceous styles.

Animals↗
PubMed2005

Follow-up and final results of the Oslo I Study comparing screen-film mammography and full-field digital mammography with soft-copy reading.

PURPOSE: To compare cancer detection rates of screen-film (SFM) and full-field digital mammography (FFDM) with soft-copy reading in a screening program including the initial positive scores for interval cancers and cancers in the subsequent screening round, and to analyze the false-negative FFDM interpretations. MATERIAL AND METHODS: Using a paired study design, 3683 women underwent SFM and FFDM in a population-based screening program. Two standard views of each breast were acquired. The images were interpreted without previous films for comparison. Independent double reading using a 5-point rating scale for probability of cancer was used for each modality. An examination was defined as positive if at least one of the two independent readers scored 2 or higher on the 5-point rating scale. SFM-positive cases were discussed in a SFM consensus meeting and FFDM-positive cases in a separate FFDM consensus meeting before recall. The study population was followed for more than 2 years so that interval cancers and screen-detected cancers in the subsequent screening round could be included. Cancer detection rates were compared using the McNemar test for paired proportions. The kappa statistic and Wilcoxon signed-rank test for matched pairs were used for comparing rating scores. The reading time was recorded for all FFDM interpretations. RESULTS: A total of 31 cancers (detection rate 0.84%) were diagnosed initially, of which SFM detected 28 and FFDM 23 (McNemar test P=0.23, discordant pair 8 and 3). Two cancers with a positive score at initial SFM reading and three with a positive score at initial FFDM reading were dismissed at SFM and FFDM consensus meetings, respectively. The difference in cancer detection after recall (discordant pair 11 and 5) was not significant (McNemar test, P=0.21). Of the 10 interval cancers and 16 screen-detected cancers in the subsequent round, 3 had true-positive SFM scores while 4 had true-positive FFDM scores in the initial reading session. A total of 38 cancers therefore had a positive result at double reading at one or both modalities, 31 at SFM and 27 at FFDM (McNemar test, P=0.48). Comparison of SFM and FFDM interpretations using the mean score for each case revealed no statistically significant difference between the two modalities (Wilcoxon signed-rank test for matched pairs; P-value=0.228). Two initial round cancers (one tumor found incidentally at work-up for a mass proved to be a simple cyst with a positive score at FFDM but a negative score at SFM, and one tumor with positive score at SFM but negative score at FFDM due to positioning failure) were excluded from the further analysis. Excluding these two cancers from comparison, there were 31% (22 of 72) false-negative SFM and 47% (34 of 72) false-negative FFDM individual interpretations. The overall mean interpretation time for normal FFDM examinations was 45 s. For most false-negative FFDM results, the reading time was shorter or longer than for normal examinations. The recorded FFDM interpretation time was noticeably short for several overlooked cancers manifesting as microcalcifications (ductal carcinoma in situ). CONCLUSION: There is no statistically significant difference in cancer detection rate between SFM and FFDM with soft-copy reading in a mammography screening program. Analysis of cancers missed at FFDM with soft-copy reading indicates that close attention has to be paid to systematic use of image display protocols.

Aged↗
PubMed2004

A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.

PURPOSE: To develop a simple scoring system for the likelihood of identifying a BRCA1 or BRCA2 mutation. METHODS: DNA samples from affected subjects from 422 non-Jewish families with a history of breast and/or ovarian cancer were screened for BRCA1 mutations and a subset of 318 was screened for BRCA2 by whole gene screening techniques. Using a combination of results from screening and the family history of mutation negative and positive kindreds, a simple scoring system (Manchester scoring system) was devised to predict pathogenic mutations and particularly to discriminate at the 10% likelihood level. A second separate dataset of 192 samples was subsequently used to test the model's predictive value. This was further validated on a third set of 258 samples and compared against existing models. RESULTS: The scoring system includes a cut-off at 10 points for each gene. This equates to >10% probability of a pathogenic mutation in BRCA1 and BRCA2 individually. The Manchester scoring system had the best trade-off between sensitivity and specificity at 10% prediction for the presence of mutations as shown by its highest C-statistic and was far superior to BRCAPRO. CONCLUSION: The scoring system is useful in identifying mutations particularly in BRCA2. The algorithm may need modifying to include pathological data when calculating whether to screen for BRCA1 mutations. It is considerably less time-consuming for clinicians than using computer models and if implemented routinely in clinical practice will aid in selecting families most suitable for DNA sampling for diagnostic testing.

Algorithms↗
PubMed2003

A collimated, high-speed outflow from the dying star V Hydrae.

Stars with masses in the range 1-8 solar masses (M(\circ)) live ordinary lives for approximately 10(9)-10(10) years, but die extraordinary deaths. First, during their death throes as asymptotic giant branch (AGB) stars they eject, over 10(4)-10(5) years, half or more of their mass in slowly expanding, spherical winds, and then, in a short (a few 100-1,000 years) and poorly understood phase, they are transformed into aspherical planetary nebula. Recent studies support the idea that high-speed, jet-like flows play a crucial role in this transformation. Evidence for such outflows is indirect, however; this phase is so short that few nearby stars are likely to be caught in the act. Here we report the discovery of a newly launched, high-speed jet-like outflow in the nearby AGB star, V Hydrae. We have detected both proper motions and ongoing evolution in the jet. These results support a model in which the jet is driven by an accretion disk around an unseen, compact companion. We also find a central, dense equatorial disk-like structure which may enable and/or enhance the formation of the accretion disk.

Journal Article↗
PubMed2002

Structure of complement receptor (CR) 2 and CR2-C3d complexes.

Using X-ray crystallography, we have determined the structure of the first two short consensus repeats (SCRs) of human complement receptor (CR) 2 in complex with C3d. These studies revealed: (i) a primary site of interaction for C3d within SCR2 of CR2, (ii) a hydrophobic patch holding SCR1 to SCR2 in a rigid V-shape, (iii) a dimer formed by interactions between SCR1 of each molecule, (iv) several non-linear sequences on C3d that interact with CR2 and (v) mutations of C3d amino acids within the co-crystal interface that resulted in decreased binding. In addition, a polymorphism that results in decreased C3d binding and introduces a new glycosylation site predicted to disrupt the dimer interface was found in the New Zealand White autoimmune mouse strain. Although the co-crystal complex results are in agreement with a subset of prior studies, our additional findings, which demonstrate an extended SCR1-SCR2 structure in solution and differences in the kinetics of ligand-receptor interactions with longer forms of CR2, have suggested a more complex receptor-ligand interaction. To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary.

Animals↗
PubMed2002

Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis.

Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild-type controls. The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.

Animals↗
PubMed2002

Ten-year experience with liver transplantation at Queen Mary Hospital: retrospective study.

OBJECTIVE: To report the experience with liver transplantation at the Queen Mary Hospital from 1991 to 2000. DESIGN: Retrospective study. SETTING: Liver transplant centre of a University teaching hospital, Hong Kong. PATIENTS: One hundred and forty-eight patients (127 adults and 21 children) who underwent a total of 155 liver transplants using 75 cadaver grafts (full-size, 67; reduced-size, 5; split, 3) and 80 living donor grafts (left lateral segment, 15; left lobe, 6; right lobe, 59) from October 1991 to December 2000 were reviewed. MAIN OUTCOME MEASURES: Graft and patient survival rate. RESULTS: The most common disease indications for liver transplantation were chronic hepatitis B-related liver disease (n=74) in adults and biliary atresia (n=14) in children. Eighteen patients had hepatocellular carcinoma. Forty-eight (31%) liver transplants (three ABO-incompatible) were performed in high-urgency situations for patients requiring intensive care. The proportion of living donor liver transplants was 47.7% in adults and 73.9% in children. The overall 1-year and 5-year patient survival rates were 82% and 77%, respectively. The survival of high-risk recipients, such as those with fulminant hepatic failure (80%), chronic hepatitis B (81%), or hepatocellular carcinoma (94%), was not inferior to that of other patients. CONCLUSION: Over the last decade, the promotion of (cadaver) organ donation through public education coupled with innovative techniques in living donor liver transplantation have enabled a liver transplantation programme to be established in Hong Kong with gratifying results.

Adolescent↗
PubMed2001

Epitope mapping using the X-ray crystallographic structure of complement receptor type 2 (CR2)/CD21: identification of a highly inhibitory monoclonal antibody that directly recognizes the CR2-C3d interface.

Complement receptor type 2 (CR2)/CD21 is a B lymphocyte cell membrane C3d/iC3b receptor that plays a central role in the immune response. Human CR2 is also the receptor for the EBV viral membrane glycoprotein gp350/220. Both C3d and gp350/220 bind CR2 within the first two of 15-16 repetitive domains that have been designated short consensus/complement repeats. Many mAbs react with human CR2; however, only one currently available mAb is known to block both C3d/iC3b and gp350/220 binding. We have used a recombinant form of human CR2 containing the short consensus/complement repeat 1-2 ligand-binding fragment to immunize Cr2(-/-) mice. Following fusion, we identified and further characterized four new anti-CR2 mAbs that recognize this fragment. Three of these inhibited binding of CR2 to C3d and gp350/220 in different forms. We have determined the relative inhibitory ability of the four mAbs to block ligand binding, and we have used overlapping peptide-based approaches to identify linear epitopes recognized by the inhibitory mAbs. Placement of these epitopes on the recently solved crystal structure of the CR2-C3d complex reveals that each inhibitory mAb recognizes a site either within or adjacent to the CR2-C3d contact site. One new mAb, designated 171, blocks CR2 receptor-ligand interactions with the greatest efficiency and recognizes a portion of the C3d contact site on CR2. Thus, we have created an anti-human CR2 mAb that blocks the C3d ligand by direct contact with its interaction site, and we have provided confirmatory evidence that the C3d binding site seen in its crystal structure exists in solution.

Animals↗
PubMed2001

Structure of complement receptor 2 in complex with its C3d ligand.

Complement receptor 2 (CR2/CD21) is an important receptor that amplifies B lymphocyte activation by bridging the innate and adaptive immune systems. CR2 ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220. We describe the x-ray structure of this CR2 domain in complex with C3d at 2.0 angstroms. The structure reveals extensive main chain interactions between C3d and only one short consensus repeat (SCR) of CR2 and substantial SCR side-side packing. These results provide a detailed understanding of receptor-ligand interactions in this protein family and reveal potential target sites for molecular drug design.

Amino Acid Sequence↗
PubMed2001

Representation of strong baseline contributions in 1H MR spectra.

A comparison is made between two optimization procedures and two data models for automated analysis of in vivo proton MR spectra of brain, typical of that obtained using MR spectroscopic imaging at 1.5 Tesla. First, a shift invariant wavelet filter is presented that provides improved performance over a conventional wavelet filter method for characterizing smoothly varying baseline signals. Next, two spectral fitting methods are described: an iterative spectral analysis method that alternates between optimizing a parametric description of metabolite signals and nonparametric characterization of baseline contributions, and a single-pass method that optimizes a complete spectral and baseline model. Both methods are evaluated using wavelet and spline models of the baseline function. Results are shown for Monte Carlo simulations of data representative of both long and short TE, in vivo 1H acquisitions.

Brain↗
PubMed2001

CD3+CD4-CD8- alphabeta-TCR+ T cell as immune regulatory cell.

Down-regulation of immune responses by regulatory T cells is one of the major mechanisms involved in the induction of tolerance to self- and alloantigens as demonstrated in a number of models of transplantation and autoimmunity. It is clear that regulatory T cells consist of different subsets. Recently a novel subset of antigen-specific alphabeta-TCR+ CD4-CD8- (double negative, DN) regulatory T cells has been found to be able to inhibit the function of the CD8+ T cells carrying the same T cell receptor specificity and prevent the rejection of skin allografts. Identification of the DN regulatory T cells and their novel mechanism of suppression can help us to understand how donor-specific transplantation tolerance can be achieved and to explain how tolerance to self-antigens can be maintained in the periphery.

Animals↗
PubMed2001

ABCC6 gene polymorphism associated with variation in plasma lipoproteins.

The ATP cassette-binding (ABC) gene superfamily contains more than 40 members, many of which are involved in cellular lipid transport. The most prominent example is ABCA1, mutations in which affect plasma high-density lipoprotein (HDL) cholesterol concentration. ABCC6 is another member of the ABC gene family, and mutations in ABCC6 were recently shown to cause pseudoxanthoma elasticum (PXE). A Canadian patient with PXE was referred for assessment of moderately severe type IV hyperlipoproteinemia with hypoalphalipoproteinemia, which was refractory to pharmacological treatment. We identified intron-exon boundaries of ABCC6 to sequence genomic DNA from this patient to find the disease mutation. We report (1) identification of a set of amplification primers for the 31 exons of ABCC6; (2) identification of the ABCC6 R>X1164 nonsense mutation in the PXE subject with dyslipidemia; (3) identification of common amino acid variants and silent nucleotide variants in ABCC6, with a range of allele frequencies across ethnic groups; (4) evidence consistent with a possible pseudogene encoding 9 exons with sequence homology to ABCC6; and (5) association of the ABCC6 R>Q1268 variant with plasma triglyceride and HDL cholesterol. The results suggest that ABCC6 may be a determinant of plasma lipoproteins.

Adult↗