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At least 631 records · Page 35Linked to original sources
PubMed2000

Automated segmentation of multiple sclerosis lesions in multispectral MR imaging using fuzzy clustering.

A method is presented for fully automated detection of Multiple Sclerosis (MS) lesions in multispectral magnetic resonance (MR) imaging. Based on the Fuzzy C-Means (FCM) algorithm, the method starts with a segmentation of an MR image to extract an external CSF/lesions mask, preceded by a local image contrast enhancement procedure. This binary mask is then superimposed on the corresponding data set yielding an image containing only CSF structures and lesions. The FCM is then reapplied to this masked image to obtain a mask of lesions and some undesired substructures which are removed using anatomical knowledge. Any lesion size found to be less than an input bound is eliminated from consideration. Results are presented for test runs of the method on 10 patients. Finally, the potential of the method as well as its limitations are discussed.

Algorithms↗
PubMed2002

Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines.

We have studied the molecular basis of resistance of multiple human leukaemia CCRF-CEM sublines to the novel antifolates ZD9331, GW1843, AG2034, PT523 and edatrexate, which use the reduced folate carrier (RFC) as their main cellular uptake route and that target different folate-dependent enzymes. Antifolate-resistant sublines established by stepwise and single-step selections displayed up to 2135-fold resistance to the selection drug, and up to 2323-fold cross-resistance to various hydrophilic antifolates. In contrast, these sublines were up to 17- and 20-fold hypersensitive to the lipophilic antifolates AG377 and trimetrexate, respectively. The total reduced folate pool of these antifolate-resistant sublines shrunk by 87-96%, resulting in up to 42-fold increased folic acid growth requirement. These sublines lost 92-97% of parental [(3)H]methotrexate influx rates. Genomic PCR single-strand conformational polymorphism analysis and sequencing revealed that most of these drug-resistant sublines harboured RFC mutations that surprisingly clustered in two confined regions in exons 2 and 3. The majority of these mutations resulted in frame-shift and/or premature translation termination and lack of RFC protein expression. The remaining mutations involved single amino acid substitutions predominantly residing in the first transmembrane domain (TMD1). Some RFC-inactivating mutations emerged during the early stages of antifolate selection and were stably retained during further drug selection. Furthermore, some sublines displayed a markedly decreased or abolished RFC mRNA and/or protein expression. This constitutes the first demonstration of clustering of multiple human RFC mutations in TMD1, thereby suggesting that it plays a functional role in folate/antifolate binding and/or translocation. This is the first molecular characterization of human RFC-associated modalities of resistance to various novel antifolates in multiple leukaemia sublines.

Base Sequence↗
PubMed2006

Classification of patterns of delirium severity scores over time in an elderly population.

OBJECTIVES: To describe and classify individual trajectories of 15-day changes in delirium severity. METHODS: A longitudinal hospital-based study was carried out with 230 medical inpatients aged 65 and over admitted to St Mary's Hospital in Montreal, Canada, between 1996 and 1999, diagnosed with delirium at enrollment, and who had at least four measurements of delirium severity during the next 15 days. Delirium severity was assessed using the Delirium Index (DI). To classify patients' individual trajectories, we applied a new method that relies on principal factor analysis and cluster analysis. We used multiple linear regression to investigate if clusters were associated with DI scores measured at an 8-week follow-up. Multivariable Cox's proportional hazards regression was used to assess whether the clusters were associated with survival over the next 12 months. RESULTS: Individual patterns were classified into five clusters: Steady (n = 89, 38.9%), Fluctuating (n = 36, 15.7%), Worsening (n = 15, 6.6%), Fast Improve-ment (n = 26, 11.3%), and Slow Improvement (n = 63, 27.5%). The Fast Improvement cluster had much lower prevalence of dementia (38.5% vs. 55.6% to 77.8% in other clusters, p = 0.003). Subjects whose 2-week patterns were classified as Fast or Slow Improvement had a significantly lower DI at 8 weeks than those in the Steady or Fluctuating clusters. The Worsening cluster had the largest percentage of deaths. The Fast Improvement and Worsening clusters initially had a high risk of death in the first 2 weeks (adjusted relative risks of approximately 3 and 6, respectively) but that risk decreased rapidly thereafter. CONCLUSION: Two-week trajectories of delirium severity were associated with short-term mortality and delirium severity at 8-week follow-up.

Aged↗
PubMed2006

Incidence of monoclonal B-cell disease in siblings of patients with multiple myeloma.

We observed clustering of monoclonal B-cell disease in siblings being screened as allogeneic donors for patients with multiple myeloma (MM) scheduled for stem cell transplantation (SCT). Of 134 asymptomatic donors, the incidence of monoclonal B-cell disease was 8/84 in siblings and 1/50 in matched unrelated donors. From an analysis of five MM families scheduled for allogeneic SCT, monoclonal B-cell disease was detected in 8/27 siblings.

B-Lymphocytes↗
PubMed1995

Analysis of Bacteroides species by pyrolysis mass spectrometry.

Two methods for the classification of isolates of the Bacteroides fragilis group were compared in a study of 133 clinical isolates and 10 reference strains. There was broad similarity between the pattern of clusters in pyrolysis mass spectrometry (PyMS), which reflects whole-cell composition, and that in conventional tests, which reflect nutritional interactions with the environment. A single large cluster was resolved by both approaches; this cluster comprised mainly strains identified as B. fragilis and was surrounded by a multiplicity of small clusters (42 in PyMS and 24 in conventional tests). Individual clusters corresponding to strains identified as Bacteroides thetaiotaomicron and Bacteroides vulgatus, respectively, were found by both techniques. However, for the remainder of strains, little correlation was evident between clustering in PyMS and that in conventional tests. Further comparison with data obtained by sodium dodecyl sulfate- polyacrylamide gel electrophoresis for this collection of strains showed equal levels of disagreement between classification based on whole-cell protein and each of the classifications described here. In previous studies of other genera, PyMS-based and conventional test-based classifications showed good agreement. It appears that the B. fragilis group presents intractable problems in phenotypic characterization.

Bacterial Typing Techniques↗
PubMed2024

Polycystic Ovary Syndrome Physiologic Pathways Implicated Through Clustering of Genetic Loci.

CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis. OBJECTIVE: This work aimed to group PCOS GWAS loci into genetic clusters associated with disease pathophysiology. METHODS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N = 62 252). Associations with clinical outcomes (type 2 diabetes [T2D], coronary artery disease [CAD], and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N = 898,130, CARDIOGRAM/UKBB, N = 547 261) and individual-level pPS in MGBB. RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) cluster 1/obesity/insulin resistance (FTO); (ii) cluster 2/hormonal/menstrual cycle changes (FSHB); (iii) cluster 3/blood markers/inflammation (ATXN2/SH2B3); (iv) cluster 4/metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (P = 6.6 × 10-29); cluster 2 with increased age of menarche (P = 1.5 × 10-4); cluster 3 with multiple decreased blood markers, including mean platelet volume (P = 3.1 ×10-5); and cluster 4 with increased alkaline phosphatase (P = .007). PCOS genetic clusters GWAS-pPSs were also associated with disease outcomes: cluster 1 pPS with increased T2D (odds ratio [OR] 1.07; P = 7.3 × 10-50), with replication in MGBB all participants (OR 1.09, P = 2.7 × 10-7) and females only (OR 1.11, 4.8 × 10-5). CONCLUSION: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

Humans↗
PubMed2006

Molecular characterization of a conserved archaeal copper resistance (cop) gene cluster and its copper-responsive regulator in Sulfolobus solfataricus P2.

Using a comparative genomics approach, a copper resistance gene cluster has been identified in multiple archaeal genomes. The cop cluster is predicted to encode a metallochaperone (CopM), a P-type copper-exporting ATPase (CopA) and a novel, archaea-specific transcriptional regulator (CopT) which might control the expression of the cop genes. Sequence analysis revealed that CopT has an N-terminal DNA-binding helix-turn-helix domain and a C-terminal TRASH domain; TRASH is a novel domain which has recently been proposed to be uniquely involved in metal-binding in sensors, transporters and trafficking proteins in prokaryotes. The present study describes the molecular characterization of the cop gene cluster in the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The polycistronic copMA transcript was found to accumulate in response to growth-inhibiting copper concentrations, whereas copT transcript abundance appeared to be constitutive. DNA-binding assays revealed that CopT binds to the copMA promoter at multiple sites, both upstream and downstream of the predicted TATA-BRE site. Copper was found to specifically modulate the affinity of DNA binding by CopT. This study describes a copper-responsive operon in archaea, a new family of archaeal DNA-binding proteins, and supports the idea that this domain plays a prominent role in the archaeal copper response. A model is proposed for copper-responsive transcriptional regulation of the copMA gene cluster.

Amino Acid Sequence↗
PubMed1995

Computerized detection of clustered microcalcifications: evaluation of performance on mammograms from multiple centers.

To investigate the performance of a computerized method for the automated detection of clustered microcalcifications in digitized mammograms from a variety of screening centers, the authors invited 118 radiologists to bring up to five mammograms to their scientific exhibit at the 1993 meeting of the Radiological Society of North America (RSNA). Forty-three mammograms from 14 sites were brought to the exhibit, where they were digitized and analyzed. Results of the analysis on the RSNA cases were compared with those obtained on a standard database of 39 mammograms collected from two centers. The performance of the detection algorithm on the RSNA images was lower than that achieved on the standard database. This lower performance was due in part to the higher fraction of very subtle clustered microcalcifications in the RSNA cases, as well as the apparent dependence of the algorithm on image characteristics (eg, contrast and noise), which varied from center to center. The authors conclude that the algorithm is robust and accurate enough to undergo clinical testing. When it is implemented clinically, the computerized scheme must be customized to the image characteristics at each specific screening center to obtain optimal performance.

Breast Diseases↗
PubMed2004

Methods for the statistical analysis of binary data in split-cluster designs.

Split-cluster designs are frequently used in the health sciences when naturally occurring clusters such as multiple sites or organs in the same subject are assigned to different treatments. However, statistical methods for the analysis of binary data arising from such designs are not well developed. The purpose of this article is to propose and evaluate a new procedure for testing the equality of event rates in a design dividing each of k clusters into two segments having multiple sites (e.g., teeth, lesions). The test statistic proposed is a generalization of a previously published procedure based on adjusting the standard Pearson chi-square statistic, but can also be derived as a score test using the approach of generalized estimating equations.

Anti-Infective Agents, Local↗
PubMed2004

Microswitch clusters to support responding and appropriate posture of students with multiple disabilities: three case evaluations.

PURPOSE: This study extended the evaluation of microswitch clusters to support responding and appropriate posture with three students with multiple disabilities. METHOD: Initially, a baseline level was established for the target response selected for each student. Then, Intervention I was implemented to increase the frequency of that response through the presentation of favourite stimuli. During Intervention II, the response was followed by favourite stimuli only if the microswitch cluster detected it in combination with appropriate posture. Post-intervention checks were carried out within 2 or 3 months from the end of Intervention II. RESULTS AND CONCLUSIONS: All students showed an increase in the frequency of the target response during Intervention I and in the percentage of times the response occurred in combination with appropriate posture during Intervention II. These changes lasted over time. The importance of microswitch clusters to enhance the performance of students with multiple disabilities was underlined.

Child↗
PubMed2003

Identification and characterization of a cluster of transcription start sites located in the E6 ORF of human papillomavirus type 16.

Human papillomavirus type 16 (HPV-16) is the prototype strain among the malignant types of HPV in the western world. The main promoter, P97, located in front of the E6 ORF, has been shown to control expression of the oncogenes E6 and E7. These oncogenes are expressed continuously in HPV-16-transformed cells. In contrast to malignant HPV types, non-malignant HPV types have separate promoters driving the expression of E6 and E7. Experiments have shown that the translation of E7 is more efficient from monocistronic than bicistronic transcripts encoding both E6 and E7. Here, identification of a cluster of transcription start sites located in the E6 ORF of HPV-16 is presented. Transcripts from this region contain the E7 ORF as the first reading frame. The cluster consists of multiple transcription start sites located around nt 441. Additional transcription start sites were identified in a cluster around nt 480. A transcription start site has been identified previously at nt 480 but has never been characterized further. The region responsible for transcription activity was mapped to nt 272-448. Mutational analysis showed that initiation of transcription is independent of a TATA-box element, which is consistent with the finding of multiple transcription start sites. Furthermore, it is shown that proteins from HeLa and SiHa nuclear cell extracts bind to the two regions at nt 291-314 and 388-411, and that these two regions influence transcription activity in a cell type-dependent manner.

Cell Line, Tumor↗
PubMed1992

Investigations of environmental conditions during cluster indicate probable vectors of unknown exogenous agent(s) of multiple sclerosis.

During the tail-end of an active cluster several environmental investigations indicated that wildbirds were very probably the vectors of the unknown exogenous agent of MS. Canine distemper and genetic-autoimmune theories were very definitely eliminated because of the unusual pattern of the cluster. Studies of several avian pathogens unveiled Marek's (MDV) and/or IBD (Gumboro) as the most likely candidates for exogenous agent of MS.

Animals↗