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PubMed1997

Molecular cytogenetics of childhood hematological malignancies.

Cytogenetic and molecular analyses are essential for the classification of childhood hematologic malignancies. Nearly all children with leukemia should have an adequate cytogenetic analysis which in 80-90% is expected to show clonal chromosomal abnormalities. Moreover, with the availability of appropriate gene probes and sophisticated molecular techniques, genetic rearrangements become detectable in the majority of leukemia patients. Genetic abnormalities often associate with particular clinical-biological characteristics of the disease. In ALL, for example, genetic alterations together with distinct immunologic and clinical features, define various subgroups. In AML, unique cytogenetic rearrangements have been identified and associated with distinct morphological subgroups. Apart from the diagnostic assessment, cytogenetic studies provide valuable prognostic information which may influence treatment choices. Molecular analysis has also become of important value in the management of children with leukemias, as it serves, for example, to identify genetic abnormalities not detected by chromosomal analysis and to monitor residual disease during treatment and follow-up. Thus, genetic analyses of leukemic cells provide information of clinical relevance as well as contributing to our understanding of leukemogenesis. Alternative classifications of acute leukemias which take into account genetic information are being proposed. The available cytogenetic and molecular data have then to be included in clinical protocols, either by selecting individualized therapies in certain leukemia subtypes or by modifying treatment according to quantification of residual disease. We are closer to our main goal which is not only to classify 100% of childhood leukemias accurately, but to cure all of them.

Child↗
PubMed2000

[Laboratory approximation to the diagnosis and typification of porphyria].

The relationship between clinical features and specific alterations of heme metabolism allows the accurate diagnosis and classification of porphyrias. The acute porphyric attack is characterized by frequently confusing clinical pattern of abdominal-psiquic- and neurological symptoms. An increased urinary excretion of porphobilinogen, which can be quickly detected by the Hoesch test, confirms the diagnosis of this acute attack. Increased plasma porphyrin levels are associated with skin lesions, which are the characteristic features of the cutaneous porphyrias. Their presence is easily and rapidly detected by a fluorimetric scanning of PBS (phosphate buffer saline) diluted samples. Characterization of the molecular defects in genes coding for the enzymes involved in the heme synthetic pathway is complementary to the biochemical methods. Molecular analysis permits an accurate classification of those biochemically unclassified patients and allows prenatal diagnosis in those homozygotic cases where a severe prognosis is suspected.

Algorithms↗
PubMed1995

Amelogenesis imperfecta--towards a new classification.

This editorial reviews the history of the classification of amelogenesis imperfecta (AI). The limitations of the existing classification systems are discussed. An alternative classification is proposed based upon the molecular defect, biochemical result, mode of inheritance and phenotype in the family involved. While not all of the criteria for the proposed classification can yet be addressed, this scheme is proposed for future classification of AI cases and families.

Amelogenesis Imperfecta↗
PubMed2003

Genetic analysis of the Saimiri breeding colony of the Pasteur Institute (French Guiana): development of a molecular typing method using a combination of nuclear and mitochondrial DNA markers.

Saimiri (Cebidae) groups a complex of species and subspecies, which present a large morphological plasticity. Genetic analysis is complicated by the absence of consensus on classification criteria and the paucity of molecular tools available for the genus. As the squirrel monkey is widely used in biomedical research, breeding centers have been established, but the genetic make up and diversity of many of the existing colonies is unknown precluding a rationale breeding policy. To develop a genetic typing strategy for the Saimiri breeding colony of Pasteur Institute of French Guiana, we have used Cytochrome b, a mitochondrial marker, and nuclear microsatellites. Cytochrome b sequences from wild-caught Saimiri boliviensis, Saimiri sciureus sciureus and S. s. collinsi reference specimens and captive animals identified 11 haplotypes, grouped into three distinct clades. An estimate of genetic variability within each captive morphotype, and of the extent of molecular divergence between the Bolivian, Guyanese and Brazilian breeds was obtained from the analysis of three nuclear microsatellites. Taxon-specific microsatellites enabled typing of F0-F3 animals, but did not differentiate Brazilian from Guyanese animals. Three locus microsatellite analysis of a representative sample from each generation showed no trend for loss of heterozygosity, and identified hybrid animals between Bolivian and the two others sub-species. These data provide novel evidence for taxonomic classification and a rationale strategy to further type the whole colony.

Animals↗
PubMed2005

Distinct molecular portraits of human failing hearts identified by dedicated cDNA microarrays.

AIMS: This study aimed to investigate whether a molecular profiling approach should be pursued for the classification of heart failure patients. METHODS AND RESULTS: Applying a subtraction strategy we created a cDNA library consisting of cardiac- and heart failure-relevant clones that were used to construct dedicated cDNA microarrays. We measured relative expression levels of the corresponding genes in left ventricle tissue from 17 patients (15 failing hearts and 2 nonfailing hearts). Significance analysis of microarrays was used to select 159 genes that distinguished between all patients. Two-way hierarchical clustering of the 17 patients and the 159 selected genes led to the identification of three major subgroups of patients, each with a specific molecular portrait. The two nonfailing hearts clustered closely together. Interestingly, our classification of patients based on their molecular portraits did not correspond to an identified etiological classification. Remarkably, patients with the highest medical urgency status (United Network for Organ Sharing, Status 1A) clustered together. CONCLUSION: With this pilot feasibility study we demonstrated a novel classification of end-stage heart failure patients, which encourages further development of this approach in prospective studies on heart failure patients at earlier stages of the disease.

Adolescent↗
PubMed2006

TCDB: the Transporter Classification Database for membrane transport protein analyses and information.

The Transporter Classification Database (TCDB) is a web accessible, curated, relational database containing sequence, classification, structural, functional and evolutionary information about transport systems from a variety of living organisms. TCDB is a curated repository for factual information compiled from >10,000 references, encompassing approximately 3000 representative transporters and putative transporters, classified into >400 families. The transporter classification (TC) system is an International Union of Biochemistry and Molecular Biology approved system of nomenclature for transport protein classification. TCDB is freely accessible at http://www.tcdb.org. The web interface provides several different methods for accessing the data, including step-by-step access to hierarchical classification, direct search by sequence or TC number and full-text searching. The functional ontology that underlies the database structure facilitates powerful query searches that yield valuable data in a quick and easy way. The TCDB website also offers several tools specifically designed for analyzing the unique characteristics of transport proteins. TCDB not only provides curated information and a tool for classifying newly identified membrane proteins, but also serves as a genome transporter-annotation tool.

Databases, Protein↗
PubMed1993

[Neuroendocrine system and its tumors].

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. The term, carcinoid, literally means carcinoma-like, was coined in 1907 to describe the histologic similarity of these tumors to carcinomas on the one hand and their generally indolent biologic behaviour on the other hand. Neuroendocrine tumours represent a group with complex biological, histological, ultrastructural and immunocytochemical properties. This concept was replaced by another classification based on results of modern techniques (electron microscopy, immunocytochemistry, molecular and DNA analyses). This permits a more reliable classification of tumours, that can be used to determine their biological behaviour and prognosis.

APUD Cells↗
PubMed2002

[Does malignant fibrous histiocytoma exist?].

Malignant fibrous histiocytoma (MFH) has come to be regarded as the most common malignant neoplasm of the mesenchymal soft tissues. It designates a spectrum of tumors which share morphologic features that allow their inclusion in a distinct clinicopathologic setting, although being not uniform in their histogenesis and pathogenesis. Clinicopathologic variants include the following: the storiform-pleomorphic form of MFH, the myxoid type of MFH, the giant cell type of MFH and the inflammatory type. The latter group, the angiomatoid variant, has been reclassified within the fibrohistiocytic tumors of low malignant potential. Tissue culture, ultrastructural and immunohistochemical studies have both endorsed or refuted the validity of the concept. As a whole, these morphologic studies which attempted to characterize MFH were not able to delineate specific markers or to describe the phenotype of this sarcoma of supposed fibrohistiocytic lineage. There is growing evidence that MFH is a second component in another sarcoma and represents a morphologic modulation resulting from tumor progression. Recent cytogenetic and molecular genetic investigations are consistent with that hypothesis: a comparative analysis between the most frequent genomic imbalances observed in series of MFH and leiomyosarcomas (LMS) demonstrated that both tumors had similar recurrent imbalances. Immunohistochemical and molecular biologic investigations have shown similar targets of chromosome deletions in both tumors. A new classification of soft tissue sarcoma based on molecular parameters is nevertheless premature. The morphologic characterization of MFH and its sub-types provides the clinician with unique information in the management of these tumors, by identifying a spectrum of tumors with well-recognized clinical profiles.

Histiocytoma, Benign Fibrous↗
PubMedDate not supplied

Serological characterization of the O-specific polysaccharide of Providencia alcalifaciens O23.

INTRODUCTION: The genus Providencia belongs to the Enterobacteriaceae family and currently consists of five species: P. alcalifaciens, P. heimbachae, P. rettgerii, P. rustigianii and P. stuartii. The serological classification scheme of P. alcalifaciens, P. rustigianii and P. stuartii includes 63 O-serogroups and 30 H-serogroups. The O-antigenic specificity is defined by the structure of the O-antigen (O-specific polysaccharide--OPS), a part of the lipopolysaccharide (LPS, endotoxin), one of the major components of the outer membrane of gram-negative bacteria and an important virulence factor of these bacteria. Among the bacteria of the Enterobacteriaceae family, the genus Providencia is one of the least studied in respect to its LPS structure and antigenic specificity. Studies of the chemical structures and the serological specificity of the O-antigens aim at the elucidation of the molecular basis of the serological classification of Providencia sp. MATERIALS AND METHODS: LPS and alkali-treated LPS of P. alcalifaciens O23 and serologically related P. rustigianii O14, P. mirabilis O13 and P. myxofaciens as well as O-antiserum against P. alcalifaciens O23 were used. Serological characterization of P. alcalifaciens O23 O-specific polysaccharide was done by use enzyme immunosorbent assay (EIA), passive hemolysis test (PHT) as well as by inhibition and sodium deoxycholate polyacrylamide gel electrophoresis (DOC-PAGE) of LPS and Western blot. RESULTS AND CONCLUSIONS: The OPS of P. alcalifaciens, O23, contains an N-(D-glucuronoyl)-N-[(R)-1-carboxyethyl]-L-lysine residue (GlcAAlaLys). The LPS of P. alcalifaciens, O23, and other LPSs containing AlaLys from Providencia and Proteus strains were tested with rabbit anti-P. alcalifiaciens O23 serum. The serological data showed that a GlcAAlaLys-associated epitope plays a role as an antigenic determinant in the P. alcalifaciens O23 OPS and revealed the particular importance of glucuronic acid and the carboxyethyl group for the binding of O23-specific antibodies.

Amino Acid Motifs↗
PubMed2002

Molecular markers that identify human astrocytomas and oligodendrogliomas.

The classification of human gliomas is currently based solely on neuropathological criteria. Prognostic and therapeutic parameters are dependent upon whether the tumors are deemed to be of astrocytic or oligodendroglial in origin. We sought to identify molecular reagents that might provide a more objective parameter to assist in the classification of these tumors. In order to identify mRNA transcripts for genes normally transcribed exclusively by oligodendrocytes. Northern blot analysis was carried out on RNA samples from 138 human gliomas. Transcripts encoding the myelin basic protein (MBP) were found in an equally high percentage of tumors that by neuropathological criteria were either astrocytic or oligodendroglial. In contrast, proteolipid protein (PLP) and cyclic nucleotide phosphodiesterase (CNP) mRNA molecules were found significantly more often in oligodendrogliomas than in astrocytomas. The strongest association with histological typing was found with the transcript for the myelin galactolipid biosynthetic enzyme UDP-galactose: ceramide galactosytransferase (CGT), which was about twice as frequently detected in tumors of oligodendroglial type. Results of glycolipid analyses were previously reported on a subset of the tumors studied herein. Statistical analyses of both molecular and biochemical data on this subset of astrocytomas, oligoastrocytomas, and oligodendrogliomas were performed to determine if a panel of markers could be used to separate astrocytic and oligodendroglial tumors. The presence of asialo GM1 (GA1) and the absence of paragloboside occurred most frequently in oligodendrogliomas. Ceramide monohexoside (CMH) levels correlated highly with the expression of mRNA for 4 myelin proteins: CGT, MBP, CNP, and PLP. The best combination of 2 markers of oligodendroglial tumors was CGT and GA1; the best combination of 3 markers was the presence of CGT, GA1, and the absence of paragloboside. We conclude that this combination of markers could be useful in distinguishing between astrocytic and oligodendroglial tumors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Classification of hepatitis C virus into major types and subtypes based on molecular evolutionary analysis.

Molecular evolutionary analysis was applied to determine the number of hepatitis C virus (HCV) types and subtypes based on all the HCV nucleotide sequences available from the DNA data banks (DDBJ, GenBank (NCBI), EMBL) and the literature. There was an excellent concordance among the types and subtypes assigned based on different HCV genomic regions. Only one HCV isolate was assigned to different HCV types based on the 5' non-coding (NC) and envelope 1 (E1) regions. The 5' NC region was well conserved and could be used to assign only types and not subtypes. From the sequence data available there were 13 subtypes based on the core region and 14 subtypes based on the E1 and non-structural protein 5 (NS5) regions.

Biological Evolution↗
PubMed2006

Classification of a diverse set of Tetrahymena pyriformis toxicity chemical compounds from molecular descriptors by statistical learning methods.

Toxicity of various compounds has been measured in many studies by their toxic effects against Tetrahymena pyriformis. Efforts have also been made to use computational quantitative structure-activity relationship (QSAR) and statistical learning methods (SLMs) for predicting Tetrahymena pyriformis toxicity (TPT) at impressive accuracies. Because of the diversity of compounds and toxicity mechanisms, it is desirable to explore additional methods and to examine if these methods are applicable to more diverse sets of compounds. We tested several SLMs (logistic regression, C4.5 decision tree, k-nearest neighbor, probabilistic neural network, support vector machines) for their capability in predicting TPT by using 1129 compounds (841 TPT and 288 non-TPT agents) which are more diverse than those in other studies. A feature selection method was used for improving prediction performance and selecting molecular descriptors responsible for distinguishing TPT and non-TPT agents. The prediction accuracies are 86.9% approximately 94.2% for TPT and 71.2% approximately 87.5% for non-TPT agents based on 5-fold cross-validation studies, which are comparable to some of earlier studies despite the use of more diverse sets of compounds. The selected molecular descriptors are consistent with those used in other studies and experimental findings. These suggest that SLMs are useful for predicting TPT potential of diverse sets of compounds and for characterizing the molecular descriptors associated with TPT.

Animals↗
PubMed1999

Post-transplant acute myeloid leukemia (PT-AML).

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

Acute Disease↗
PubMed1997

Convergent evolution in invertebrates.

Resemblance between animal taxa may be due to convergence rather than to recent common ancestry. Constraints on biological materials and adaptation to particular habits or habitats will produce widespread convergence. How may we distinguish the two causes of resemblance? The relationship between convergence and taxonomy is discussed, demonstrating that the choice of taxonomic method will itself determine the extent to which convergence is perceived. In particular, cladistic analysis based on parsimony will tend to minimise and thus conceal convergence: neither the resulting cladogram nor a consistency index derived from it can be used to assess the prevalence of convergence. With any taxonomic system, there can be no substitute for evaluation of the morphological characters used. Complementary use of molecular characters shows promise: we wait further understanding of constraints in genetic evolution and of the possibilities of convergence at this level also. These general principles are illustrated with a range of examples from within and between invertebrate phyla: the phylogeny of Cnidaria and Platyhelminthes cannot be traced with certainty, but where the fossil record allows clear rooting, as for the echinoderms and in particular the echinoids, combination of morphological and molecular methods has made much progress. Sub-groups within a phylum, for example opisthobranch molluscs and the dipteran Phoridae, may show an uncontested phylogeny, and here studies have precisely identified convergence and shown that it may be the commoner cause of resemblance. Adaptation to exacting environments shown by terrestial and freshwater nemertines may also result in a predominance of convergent resemblance. Traditional grouping of phyla breaks down on re-examination of supposedly key characters, such as segmentation, body cavities, germ layers and symmetry, each of which must have had multiple origins: nor are developmental stages (especially not larvae) a reliable guide to relationships. Demarcation of phyla may be difficult, as with arthropods, and location of phyla is even more difficult, due to their early and rapid radiation. Over-simplified definition of characters has bedevilled invertebrate classification and the use of molecular data has not yet resolved the major controversies. The question "How common is convergence?' remains unanswered and may be unanswerable. Our examples indicate that even the minimum detectable levels of convergence are often high, and we conclude that at all levels convergence has been greatly underestimated.

Animals↗
PubMed2005

Two-dimensional electrophoresis protein profiling as an analytical tool for human acute leukemia classification.

Two-dimensional electrophoresis (2-DE) was used to profile the proteins of leukemic cells from 61 cases of akute leukemia (AL) characterized by the French-American-British (FAB) classification. The differentially expressed protein spots were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). The distinct protein profiles (DPPs) of AL FAB subtypes were explored successfully, including acute myeloid leukemia (AML), its subtypes (M2, M3, and M5), and acute lymphoid leukemia (ALL), which were homogeneous within different samples of the same subgroup but clearly differed from all other subgroups. We also found a group of proteins differentially expressed between AL cells and normal white blood cells. Among the DPPs of AL subtypes, some proteins have been reported, but most of them were first reported here to mark AML differentiation and to discriminate AML from ALL. These data show that 2-DE protein profiling could be used as an analytical tool for facilitating molecular definition of human AL classification and understanding the mechanism of leukemogensis, and the extension of the present analysis to the currently less well-defined AL will identify additional subgroups and may promote the identification of new targets for specific treatment approaches.

Acute Disease↗
PubMed2004

Partitioning in binary-transformed chemical descriptor spaces.

Here we describe a statistically based partitioning method called median partitioning (MP), which involves the transformation of value distributions of molecular property descriptors into a binary classification scheme. The MP approach fundamentally differs from other partitioning approaches that involve dimension reduction of chemical spaces such as cell-based partitioning, since MP directly operates in original, albeit simplified, chemical space. Modified versions of the MP algorithm have been implemented and successfully applied in diversity selection, compound classification, and virtual screening. These findings have demonstrated that dimension reduction techniques, although elegant in their design, are not necessarily required for effective partitioning of molecular datasets. An attractive feature of statistical partitioning approaches such as decision tree methods or MP is their computational efficiency, which is becoming an important criterion for the analysis of compound databases containing millions of molecules.

Algorithms↗