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PubMed2026

Cytogenetic Diversity of Variant Philadelphia Translocations in Chronic Myeloid Leukemia.

INTRODUCTION: Chronic myeloid leukemia (CML) is a disease characterized by Philadelphia (Ph) translocations. These translocations can be classical or variant. The structural features and diagnostic implications of variant Philadelphia translocations remain incompletely defined, and they display considerable cytogenetic heterogeneity. METHODS: In this retrospective study, variant Ph translocations identified by conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) were systematically classified among 639 patients diagnosed with CML. A total of 35 patients with variant Ph translocations were included in the analysis. Molecular follow-up data, when available, were assessed using RT-qPCR analyses in a subset of patients. RESULTS: Chromosome analysis revealed 2 simple and 33 complex variant Ph translocations. FISH analysis, performed in 20 patients, identified deletions involving BCR, ABL1, or both in a limited number of cases. Additional chromosomal abnormalities and secondary translocations accompanied variant Ph translocations in four patients. The partner chromosomes involved in variant Ph translocations showed marked diversity, involving multiple chromosomal loci. CONCLUSION: Variant Philadelphia chromosome translocations in CML exhibit substantial cytogenetic diversity, reflecting the complexity of their underlying genomic architecture. The rarity and heterogeneity of these rearrangements complicate their classification and interpretation in routine diagnostic practice. Descriptive reporting of variant Ph translocations may contribute to a better understanding of their diagnostic complexity and support more accurate cytogenetic interpretation in CML.

Humans↗

PubMed2006

GenoMycDB: a database for comparative analysis of mycobacterial genes and genomes.

Several databases and computational tools have been created with the aim of organizing, integrating and analyzing the wealth of information generated by large-scale sequencing projects of mycobacterial genomes and those of other organisms. However, with very few exceptions, these databases and tools do not allow for massive and/or dynamic comparison of these data. GenoMycDB (http://www.dbbm.fiocruz.br/GenoMycDB) is a relational database built for large-scale comparative analyses of completely sequenced mycobacterial genomes, based on their predicted protein content. Its central structure is composed of the results obtained after pair-wise sequence alignments among all the predicted proteins coded by the genomes of six mycobacteria: Mycobacterium tuberculosis (strains H37Rv and CDC1551), M. bovis AF2122/97, M. avium subsp. paratuberculosis K10, M. leprae TN, and M. smegmatis MC2 155. The database stores the computed similarity parameters of every aligned pair, providing for each protein sequence the predicted subcellular localization, the assigned cluster of orthologous groups, the features of the corresponding gene, and links to several important databases. Tables containing pairs or groups of potential homologs between selected species/strains can be produced dynamically by user-defined criteria, based on one or multiple sequence similarity parameters. In addition, searches can be restricted according to the predicted subcellular localization of the protein, the DNA strand of the corresponding gene and/or the description of the protein. Massive data search and/or retrieval are available, and different ways of exporting the result are offered. GenoMycDB provides an on-line resource for the functional classification of mycobacterial proteins as well as for the analysis of genome structure, organization, and evolution.

Bacterial Proteins↗

PubMed2001

Texture analysis of fluorescence microscopic images of colonic tissue sections.

The aim of this study was to assess the potential of texture analysis for the characterization of fluorescence images from colonic tissue sections stained with a novel and selective fluoroprobe, Rhodamine B-phenylboronic acid. Fluorescence microscopy images of colonic healthy mucosa (n = 35) and adenocarcinomas (n = 35) were digitally captured and subjected to image texture analysis. Textural features derived from the grey level co-occurrence matrix were calculated. A modified version of the multiple discriminant analysis criterion was used to choose an appropriate subset of features. A minimum Mahalanobis distance, linear discriminant classifier and a simple evaluation 'score' method were used to classify image feature data into the two categories. A subset of four textural features was selected and used for the description and classification of each image field. They were found appropriate to correctly classify 95% of the images into the two classes, using two different classifiers. These features contained information about local homogeneity and grey level linear dependencies of the image. This study demonstrated that texture analysis techniques could provide valuable diagnostic decision support in a complex domain such as colorectal tissue.

Adenocarcinoma↗

PubMed2005

In silico analysis of crustacean hyperglycemic hormone family.

Through multiple sequence alignment and phylogenetic analysis, the subgrouping of the crustacean hyperglycemic hormone (CHH) family was updated using the most complete, nonredundant sequence data set. All sequences from insects were clustered into a distinct subbranch with characters closer to CHH subfamily I. Several sequences that are controversial in their nomenclature and classification are discussed. The motif configuration of CHHs differs from that of molt-inhibiting hormone or gonad-inhibiting hormone in both N and C termini. These two motifs approach each other in tertiary structure models, and the motif preference reveals the critical roles of these regions in functional specificity. Two types of exon organizations of the CHH family genes were observed. Four-exon Chh genes were found in a wide range of pan-crustacean (crustacean and hexapod) taxa, except for the penaeid species, from which the 3-exon Chh genes were reported. Meanwhile, the 3-exon structure was found in the Mih gene and Moih genes from one brachyuran species. Combining gene scan skill and exon splicing rules found in this study, we define three more novel sequences from two insect genomes. The pattern of the exon-exon junction within the mature peptide segment is preserved in all CHH family members.

Amino Acid Motifs↗

PubMed1984

What affects fetal pulmonary maturation during diabetic pregnancy?

Previous studies differ as to whether the fetus of the woman with diabetes mellitus has altered formation of lung surfactant. The factors responsible for these differences remain unclear. In this study, measures of blood glucose control, including birth weight percentile and the presence of factors potentially influencing fetal pulmonary maturation, such as diabetic class, maternal chronic hypertension, and preeclampsia, were compared with the amniotic fluid lecithin/sphingomyelin ratio, phosphatidylglycerol, and phosphatidylinositol within a group of 90 diabetic pregnancies. The factors were evaluated in combination with the techniques of canonical correlation and multiple regression analysis. Gestational age had the strongest effect in determining levels of amniotic fluid phospholipids, and hypertension was found to significantly accelerate the appearance of phosphatidylgycerol (p less than 0.05). The effect of hypertension was one third as important as that of gestational age. Neither diabetic blood glucose control, White classification, nor the remaining explanatory variables were found to play a significant role in determining the amniotic fluid phospholipid levels. This study suggests that, in the clinical management of diabetes, gestational duration remains the single most important determinant of amniotic fluid phospholipid levels.

Amniotic Fluid↗

PubMed2000

Neural network modeling of risk assessment in child protective services.

The advantages of using neural network methodology for the modeling of complex social science data are demonstrated, and neural network analysis is applied to Washington State Child Protective Services risk assessment data. Neural network modeling of the association between social worker overall assessment of risk and the 37 separate risk factors from the State of Washington Risk Assessment Matrix is shown to provide case classification results superior to linear or logistic multiple regression. The improvement in case prediction and classification accuracy is attributed to the superiority of neural networks for modeling nonlinear relationships between interacting variables; in this respect the mathematical framework of neural networks is a better approximation to the actual process of human decision making than linear, main effects regression. The implications of this modeling advantage for evaluating social science data within the framework of ecological theories are discussed.

Child↗

PubMed2006

INVHOGEN: a database of homologous invertebrate genes.

Classification of proteins into families of homologous sequences constitutes the basis of functional analysis or of evolutionary studies. Here we present INVertebrate HOmologous GENes (INVHOGEN), a database combining the available invertebrate protein genes from UniProt (consisting of Swiss-Prot and TrEMBL) into gene families. For each family INVHOGEN provides a multiple protein alignment, a maximum likelihood based phylogenetic tree and taxonomic information about the sequences. It is possible to download the corresponding GenBank flatfiles, the alignment and the tree in Newick format. Sequences and related information have been structured in an ACNUC database under a client/server architecture. Thus, complex selections can be performed. An external graphical tool (FamFetch) allows access to the data to evaluate homology relationships between genes and distinguish orthologous from paralogous sequences. Thus, INVHOGEN complements the well-known HOVERGEN database. The databank is available at http://www.bi.uni-duesseldorf.de/~invhogen/invhogen.html.

Animals↗

PubMed1979

Predicting suicide using the Rorschach Inkblot Test.

Three hundred and seventy-five Rorschach protocols were scored blind and then divided into three groups: psychiatric controls, suicide attempts, and suicide effectors. Using the stepwise procedure of multiple discriminant analysis a trio of formulas, composed of six weighted variables each, and a constant, were constructed to apply to each of the three groups based on a test sample of 100 subjects in each group. Cross validation results on a new sample of 25 subjects in each group predicted classification with 52% overall accuracy at step six (chance .33). Internal reliability tests showed all values significant beyond .001. Discussion integrates the test data into the literature on suicide, and attends to the problem of overlap of predictability which occurs with most prediction scales.

Adolescent↗

PubMed2006

Global expression-based classification of lymph node metastasis and extracapsular spread of oral tongue squamous cell carcinoma.

Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC) progression. The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making for improved management of OTSCC patients. Global expressional profiles were obtained for 25 primary OTSCCs, where 11 cases showed lymph node metastasis (pN+) histologically and 14 cases were nonmetastatic (pN-). Seven of pN+ cases also exhibited extracapsular spread (ECS) of metastatic nodes. Multiple expression indices were used to generate signature gene sets for pN+/- and ECS+/- cases. Selected genes from signature gene sets were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The classification powers of these genes were then evaluated using a logistic model, receiver operating characteristic curve analysis, and leave-one-out cross-validation. qRT-PCR validation data showed that differences at RNA levels are either statistically significant (P < .05) or suggestive (P < .1) for six of eight genes tested (BMP2, CTTN, EEF1A1, GTSE1, MMP9, and EGFR) for pN+/- cases, and for five of eight genes tested (BMP2, CTTN, EEF1A1, MMP9, and EGFR) for ECS+/- cases. Logistic models with specific combinations of genes (CTTN+MMP9+EGFR for pN and CTTN+EEF1A1+MMP9 for ECS) achieved perfect specificity and sensitivity. Leave-one-out cross-validation showed overall accuracy rates of 85% for both pN and ECS prediction models. Our results demonstrated that the pN and the ECS of OTSCCs can be predicted by gene expression analyses of primary tumors.

Adult↗

PubMed2005

Computational prediction of SEG (single exon gene) function in humans.

Human genes are often interrupted by non-coding, intragenic sequences called introns. Hence, the gene sequence is divided into exons (coding segments) and introns (non-coding segments). Consequently, a majority of them are multi exon genes (MEG). However, a considerable amount of single exon genes (SEG) are present in the human genome (approximately 12%). This amount is sizeable and it is important to probe their molecular function and cellular role. Hence, we performed a genome wide functional assignment to 3750 SEG sequences using PFAM (protein family database), PROSITE (database of biologically meaningful signatures or motifs) and SUPERFAMILY (a library covering all proteins of known 3 dimensional structure). PFAM assigned 13% SEG to trans-membrane receptor genes of the G-protein coupled receptor (GPCR) family and showed that a majority of SEG proteins have DNA binding function. PROSITE identified 336 unique motif types in them and this accounts for 25% of all known patterns, with a majority having PHOSPHORYLATION and ACETYLATION signals. SUPERFAMILY assigned 33% SEG to the membrane all alpha (proteins containing alpha helix structural elements according to SCOP (structural classification of proteins) definition). Functional assignment of SEG proteins at multiple levels (sequence signals, sequence families, 3D structures) using PFAM, PROSITE and SUPERFAMILY is envisioned to suggest their selective and predominant molecular function in cellular systems. Their function as DNA binding, phosphorylating, acetylating and house-keeping agents is intriguing. The analysis also showed evidence of SEG expression and retro-transposition. However, this information is inadequate to draw concerted conclusion on the prevalent role played by these proteins in cellular biology. A complete understanding of SEG function will help to explore their role in cellular environment. The derived datasets from these analyses are available at http://sege.ntu.edu.sg/wester/intronless/human/.

Computational Biology↗

PubMed1999

Intestinal obstruction in the elderly. Prognostic factors of mortality.

OBJECTIVES: To analyze mortality-related factors in elderly patients who were operated on for intestinal obstruction, and to determine whether advanced age worsened the morbidity and mortality rates. METHODS: In this prospective study we analyzed 188 patients older than 69 years who were operated on for intestinal obstruction. Group 1 consisted of 82 patients aged between 70 and 79 years, and group 2 consisted of 106 patients aged 80 years and older. We compared the distribution of clinical features and outcomes between the two groups, and determined factors related with mortality (chi-squared test with Yates' correction, Student's t test and multiple logistic regression analysis). RESULTS: The incidence of heart disease was 11% in group 1 and 35% in group 1 (p = 0.0003). There was no difference between the groups in any of the other factors analyzed. Univariate analysis identified as mortality-related factors perianesthetic risk (American Society of Anesthesiologists' Physical Status classification) (p = 0.0005), presence of metastases (p = 0.0001) and delay in surgery (t value = 3.043, p = 0.0027). CONCLUSIONS: Mortality due to surgery for intestinal obstruction in elderly patients is related to perianesthetic risk and delay in surgery. Older age does not increase the morbidity or mortality rates for this type of surgery.

Age Distribution↗

PubMed2000

[Differentiation of malignant and non-malignant origin of ascites by determination of levels of cholesterol and lactate dehydrogenase in ascitic fluid is not absolute].

The authors Castaldo et al. (Clin. Chem., 1994, 30: 478-83) state, that the ascitic lactate dehydrogenase and ascitic cholesterol association correctly identified 100% of malignant ascites from ascites associated with cirrhosis and/or hepatocellular carcinoma, with help of stepwise multiple linear discriminant analysis. The free software Capsules--Ascites is via internet available (http:¿www.leeds.ac.uk/acb), which use the mathematical formula from this article. As we argue, Castaldo's state is not correct. Three independent multidimensional statistical methods--bivariate reference regions (program EVAL-KIT), cluster analysis (program BioAnalyst), geometrical distance classification (program GEODICLA) applicated on Castaldo's original data showed that lactate dehydrogenase and cholesterol have not satisfactory absolute discriminative power between malignant from nonmalignant ascites in general, but the probability to determinate the right diagnosis is about 91-93%. Research conducted in correctly selected probands should provide information which is valid not only for the selected sample but for the entire population, to achieve more generally valid conclusions, useful for practical decisions. In addition, in the compiled table show we sensitivity and specificity of different laboratory parameters publicated in 11 original articles in the nineties, all with diagnostic efficiency less 100%.

Ascites↗

PubMed1997

Modal profiles for the Halstead-Reitan Neuropsychological Battery for Children.

Modal Profile Analysis was used to cluster students (aged 9 to 14 years) on 16 subtest scores from the Halstead-Reitan Neuropsychological Battery for Children (HRNB-C). This analysis produced eight modal profile types, all of which were replicated in multiple samples. An initial attempt to establish external validity indicated that the modal groups display dissimilar patterns of performance on independent variables. The present typology is compared to similar typologies developed with adult neuropsychological data. In sum, the current classification system provided less coverage than the adult typologies, but produced more unique or homogeneous modal groups. Discussion focuses on potential clinical and research uses of the modal HRNB-C profiles.

Journal Article↗

PubMed2004

Gastrointestinal lymphoma in Thailand: a clinicopathologic analysis of 120 cases at Siriraj Hospital according to WHO classification.

Clinicopathologic information of gastrointestinal (GI) lymphoma in Southeast Asia is lacking. A retrospective analysis of 120 cases of GI lymphoma in Thailand diagnosed at Siriraj Hospital based on WHO classification was performed. All were non-Hodgkin lymphoma (NHL). The peak age was in the sixth and seventh decades; a slight male preponderance was observed. Sites of involvement included stomach (49.2%), intestine (46.7%), and multiple sites (4.2%). There were 104 cases of primary GI lymphoma (86.7%) and 16 cases of secondary GI lymphoma (13.3%). Presenting GI symptoms were more common in the former; while superficial lymphadenopathy and fever were more common in the latter. Mass lesions were observed in both groups (72.1% vs 56.3%). Localized and advanced diseases were found in 68.3% and 31.7% of primary GI lymphomas, respectively. The most common type of lymphoma in both groups was diffuse large B-cell lymphoma. Lymphoepithelial lesions (LEL) were not significantly different between the two groups (58.2% vs 42.9%), but Helicobacterpylori infection was significantly associated with primary gastric lymphoma (p < 0.0001). The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone. GI lymphomas in Thailand are mostly primary B-cell NHL. LEL is not indicative of primary GI lymphoma, but H. pylori infection is closely associated with primary gastric lymphoma. A prospective study to determine the treatment of choice for localized GI lymphoma is needed.

Adolescent↗

PubMed2005

[Study of high-risk factors of surgical site infection after cesarean section].

OBJECTIVE: To study the high-risk factors of surgical site infection after cesarean section. METHODS: We retrospectively reviewed cesarean section cases with surgical site infection and evaluated the high-risk factors related to the infection. RESULTS AND CONCLUSIONS: Totally 14 factors were identified as the high-risk factors such as obesity, inadequate antibiotic prophylaxis, low ferrohemoglobin level, existing infection before hospitalization, multiple vaginal and anal examinations, premature rupture of membranes, and prolonged operative time. The 7 factors such as emergency operation were not shown to be significant high-risk factors. The probability of parturient with frequently vaginal examination to acquire infection following cesarean section was 75.2%, which was judged by classification analysis. A stepwise addition of the factors for analysis showed some difference in the predicted probability, which was 75.2% for inadequate antibiotic prophylaxis, 82.4% for low ferrohemoglobin level, 81.7% for prolonged operative time, 86.3% for obesity, 83.7% for premature rupture of the membranes, and 84.9% for existing infection before hospitalization.

Cesarean Section↗

PubMedDate not supplied

Can staging systems for endometriosis based on anatomic location and lesion type predict pregnancy rates?

OBJECTIVE: Development of an endometriosis classification system based on empirically derived stages of the disease, to supplant the Acosta (1973), Kistner (1977), and American Fertility Society (1985) classifications, which are based on arbitrarily defined stages and often fail to predict pregnancy rates. DESIGN: Retrospective cohort analysis. SETTING: University infertility clinic. PATIENTS AND METHODS: Women with endometriosis and > or = 1 year of infertility. Diagnosis of endometriosis was made by direct visualization, with type of lesion (implant or adhesion) at multiple sites recorded; total of 202 patients. All diagnosed infertility problems were treated based on semen analysis, postcoital test, and endometrial biopsy. Pregnancy rates were analyzed by life-table and cluster analyses, and combinations of site and type were also analyzed by Cox's regression model. RESULTS: No individual anatomic site or type significantly affected prognosis, nor was any cluster useful for predicting outcome. CONCLUSION: Anatomic site and type of lesion are insufficient for predicting fertility when used as sole components of a clinical staging system for endometriosis.

Adult↗

PubMed2005

Reproducible clusters from microarray research: whither?

MOTIVATION: In cluster analysis, the validity of specific solutions, algorithms, and procedures present significant challenges because there is no null hypothesis to test and no 'right answer'. It has been noted that a replicable classification is not necessarily a useful one, but a useful one that characterizes some aspect of the population must be replicable. By replicable we mean reproducible across multiple samplings from the same population. Methodologists have suggested that the validity of clustering methods should be based on classifications that yield reproducible findings beyond chance levels. We used this approach to determine the performance of commonly used clustering algorithms and the degree of replicability achieved using several microarray datasets. METHODS: We considered four commonly used iterative partitioning algorithms (Self Organizing Maps (SOM), K-means, Clutsering LARge Applications (CLARA), and Fuzzy C-means) and evaluated their performances on 37 microarray datasets, with sample sizes ranging from 12 to 172. We assessed reproducibility of the clustering algorithm by measuring the strength of relationship between clustering outputs of subsamples of 37 datasets. Cluster stability was quantified using Cramer's v2 from a kXk table. Cramer's v2 is equivalent to the squared canonical correlation coefficient between two sets of nominal variables. Potential scores range from 0 to 1, with 1 denoting perfect reproducibility. RESULTS: All four clustering routines show increased stability with larger sample sizes. K-means and SOM showed a gradual increase in stability with increasing sample size. CLARA and Fuzzy C-means, however, yielded low stability scores until sample sizes approached 30 and then gradually increased thereafter. Average stability never exceeded 0.55 for the four clustering routines, even at a sample size of 50. These findings suggest several plausible scenarios: (1) microarray datasets lack natural clustering structure thereby producing low stability scores on all four methods; (2) the algorithms studied do not produce reliable results and/or (3) sample sizes typically used in microarray research may be too small to support derivation of reliable clustering results. Further research should be directed towards evaluating stability performances of more clustering algorithms on more datasets specially having larger sample sizes with larger numbers of clusters considered.

Cluster Analysis↗

PubMed1996

Identification of single and dual infections with distinct subtypes of human immunodeficiency virus type 1 by using restriction fragment length polymorphism analysis.

The simultaneous presence of multiple HIV-1 subtypes has become common in communities with the growth of the pandemic. As a consequence, the potentiality for an increased frequency of HIV-1 mixed infections caused by viruses of distinct subtypes could be expected. Thus, there is a need to estimate the prevalence and geographic distribution of infections caused by viruses of a singular subtype as well as coinfections caused by two or more HIV-1 strains of distinct subtypes. To address this need, we have developed a genetic method based on restriction fragment length polymorphism (RFLP) to screen for these two types of infections within infected populations. In this assay, restriction enzymes may be used to predict the phylogroup of HIV-1 infected samples. A 297 bp pol fragment spanning the entire viral protease gene and a 311 bp fragment of the p24 gag region are used for this analysis. The viral regions are amplified by nested PCR using DNA templates from uncultured peripheral blood mononuclear cells (PBMC) or virus culture. Classification of HIV-1 strains to well defined subtypes B, D, F, and A/C is done by sequential endonuclease restriction analysis of a PCR amplified-protease gene followed by analysis of the p24 gag region. The electrophoretic migration patterns visualized by ethidium bromide staining or by radiolabeled probes are then determined on a 10% polyacrylamide gel. In infections caused by viruses of a singular subtype, a single restriction pattern is detected, whereas in multiple infections caused by two or more viral strains of different subtypes, the combination of different digestion patterns are observed in infected individuals. Using this methodology we have screened for genetic variations in HIV-1 proviral DNA from thirty-three Brazilian samples. Our RFLP procedure classified thirty-two samples as single infections caused by viruses of subtypes B (31) and F (1), and one sample as dual infection caused by distinct viral strains. Subsequent sequence and phylogenetic analysis of the viral protease gene in lymphocytes of all these patients confirmed our RFLP findings in single infections, and demonstrated the existence of two distinct HIV-1 strains of subtypes F and D in a patient which lymphocytes showed the simultaneous presence of two different digestion patterns. As up to now, single infections caused by subtype D variants were not identified in Brazil, our data provide the first evidence of subtype D HIV-1 in this country. Because sequencing of HIV proviral DNA is not particularly practical for large-scale molecular epidemiological studies, the protease/gag-based RFLP screening method will be useful to predict the phylogroup of HIV-1, and to identify multiple infections caused by HIV-1 strains of distinct subtypes. We believe that this information is crucial for both evaluation of the HIV-1/AIDS pandemic and intervention strategies.

Adult↗