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PubMed2002

The transporter classification (TC) system, 2002.

The Transporter Classification (TC) system is a functional/phylogenetic system designed for the classification of all transmembrane transport proteins found in living organisms on Earth. It parallels but differs from the strictly functional EC system developed decades ago by the Enzyme Commission of the International Union of Biochemistry and Molecular Biology (IUBMB) for the classification of enzymes. Recently, the TC system has been adopted by the IUBMB as the internationally acclaimed system for the classification of transporters. Here we present the characteristics of the nearly 400 families of transport systems included in the TC system and provide statistical analyses of these families and their constituent proteins. Specifically, we analyze the transporter types for size and topological differences and analyze the families for the numbers and organismal sources of their constituent members. We show that channels and carriers exhibit distinctive structural and topological features. Bacterial-specific families outnumber eukaryotic-specific families about 2 to 1, while ubiquitous families, found in all three domains of life, are about half as numerous as eukaryotic-specific families. The results argue against appreciable horizontal transfer of genes encoding transporters between the three domains of life over the last 2 billion years.

Animals↗
PubMed2002

Use of predictive modeling for Propionibacterium strain classification.

Computed data analysis of biochemical or molecular profiles is currently used in studies of microbial taxonomy, epidemiology, and microbial diversity. We assessed the use of Partial Least Squares (PLS) regression for multivariate data analysis in bacteriology. We identified clear relationships between RAPD profiles of propionibacteria strains and their species classification, autolytic capacities, and their origins. The PLS regression also predicted species identity of some strains with RAPD profiles partially related to those of reference strains. The PLS analysis also allowed us to identify key characteristics to use to classify strains. PLS regression is particularly well adapted to i) describing a collection of bacterial isolates, ii) justifying bacterial groupings using several sets of data, and iii) predicting phenotypic characters of strains that have been classified by routine typing methods.

Autolysis↗
PubMed2004

Molecular epidemiology of HIV: tracking AIDS pandemic.

BACKGROUND: Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) epidemic is a global threat to maternal and child health, especially in developing countries. It is estimated that 800 000 children are infected and 580 000 children die of AIDS-related illnesses every year. Molecular epidemiology has been a useful tool in analyzing the origin of HIV and tracking the course of global HIV spread. This article provides an overview of recent advances in the field of molecular epidemiology of HIV across the world, and discuss the biological implications. METHODS: Based on the near full-length or partial nucleotide sequence information, the phylogeny and recombinant structure of HIV strains are analyzed. Using genotype classification of HIV as a molecular marker, the origin and the genesis of HIV epidemic are investigated. RESULTS: The HIV-1 group M, a major HIV group responsible for current AIDS pandemic, began its expansion in human population approximately 70 years ago and diversified rapidly over time, now comprising a number of different subtypes and circulating recombinant forms (CRF). Of note, recent studies revealed that new recombinant strains are arising continually, becoming a powerful force in the spread of HIV-1 across the globe. CONCLUSIONS: Global dissemination of HIV is a dramatic and deadly example of recent genome emergence and expansion. Molecular epidemiological investigation is expected to provide information critical for prevention and future vaccine strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Advances in acute lymphoblastic leukemia.

DATA SOURCES: Current literature. DATA SYNTHESIS: Acute lymphoblastic leukemia (ALL) is a stem cell disorder characterized by an overproduction of lymphoblasts in the bone marrow that eventually spill into circulation, producing lymphocytosis. As with the other acute leukemias, the most common symptoms experienced by patients include fatigue, bleeding, and recurrent infections resulting from the suppression of normal hematopoiesis in the bone marrow by the accumulating blasts. ALL primarily affects children and exhibits the best response to standard chemotherapy as compared to acute myeloblastic leukemias (AML). Further, remission rates are highest among ALL patients, many of whom are experiencing sustained remissions suggesting cure. In light of early treatment successes, researchers began to investigate modifications of standard treatment regimens to accommodate variability in weight, age, and response to therapy among children with ALL. Individualized treatment plans were implemented where some patients received a reduced intensity course of therapy to minimize drug toxicity while others received drug intensification to maximize response. More recently, research efforts have been directed at the elucidation of leukemogenic mechanisms implicated in ALL to identify specific protein mutants that can be used to design drugs tailored to interfere with the activity of these mutant protein targets. Identification of chimeric proteins produced from chromosomal translocations and gene expression profiles from microarray analyses are the primary techniques used to identify the potential therapeutic targets. CONCLUSION: Several reliable prognostic indicators have been identified and are being used to improve therapeutic planning and outcome prediction in ALL patients. Individualized treatment regimens have been developed based on the specific characteristics of each patient to minimize treatment related adverse events and maximize response. Through the use of cytogenetic, molecular, and microarray testing, ALL classification schemes have improved and potential therapeutic targets have been identified. It is anticipated that the next major advance in the treatment of ALL will involve the use of designer therapies developed to specifically interfere with particular molecular abnormalities producing the leukemogenic aberration to the normal signal transduction pathways.

Adult↗
PubMed1983

A new approach to the classification of human leukaemias: measurement of the relative abundance of a specific RNA sequence by means of molecular hybridisation.

A recombinant plasmid library representing polyadenylated RNAs in the leucocytes of a Ph1-positive chronic granulocytic leukaemia (CGL) has been constructed. One recombinant (designated pCG14) isolated from this library contains a DNA sequence complementary to a small polyadenylated RNA that is abundant in RNA from CGL leucocytes. The relative concentrations of pCG14 RNA in the RNAs from a variety of normal and leukaemic leucocytes and human haemopoietic cell lines have been measured with a molecular hybridisation assay. This has shown that pCG14 RNA is 10 to 50 times more abundant in RNA from CGL leucocytes than in the RNAs from these other cells. The data indicate that the occurrence of pCG14 RNA in high abundance is sufficiently characteristic of a CGL leucocyte population to distinguish it from other populations of leucocytes. They suggest that the measurement of the concentrations of specific RNA species in leucocyte RNA by means of molecular hybridisation with cloned complementary DNAs may provide additional markers for the objective classification of human leukaemias which could be particularly useful since the method exploits a criterion different from any currently in use.

Autoradiography↗
PubMed2004

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma.

Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic classification of these cancers is frequently complicated by the highly similar appearance in routine histology, and additional molecular markers could significantly improve tumor classification. A combination of three independent statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in 101 highly significant probe sets that clearly discriminate between EWS and RMS. We identified novel marker transcripts that have not been previously associated with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1). Expression levels for selected candidate genes were validated by quantitative real-time reverse-transcription PCR. Furthermore, to identify biologically meaningful trends, functional annotations were assigned to 946 genes differentially expressed between EWS and RMS (t-test). Genes involved in protein biosynthesis (n = 28) and complex assembly (n = 9), lipid metabolism (n = 23), energy generation (n = 22), and mRNA processing (n = 11) were expressed significantly higher in EWS. Thus, functional annotation of tumor-specific genes reveals detailed insights into tumor biology and differentiation-specific expression patterns and gives important clues related to the possible cellular origin of these pediatric tumors. Supplementary material for this article is available at the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

Biomarkers, Tumor↗
PubMed2006

Prediction of milk/plasma drug concentration (M/P) ratio using support vector machine (SVM) method.

PURPOSE: Development of reliable computational models to predict/classify milk-to-plasma (M/P) drug concentration ratio remains a challenging object. Support vector machine (SVM) method, as a new algorithm, was constructed to distinguish the potential risk of drugs to nursing infants. METHODS: Each drug was represented by a large pool of descriptors, of which five were found to be most important for constructing the predictive models. Next, two classification models, linear discriminant analysis (LDA) and SVM, were developed with bootstrapping validation based on the selected molecular descriptors. RESULTS AND CONCLUSIONS: The classification accuracy of training set and test set for SVM was 90.63 and 90.00%, respectively. The total accuracy for SVM was 90.48%, which was higher than that of LDA (77.78%). Comparison of the two methods shows that the performance of SVM was better than that of LDA, which implies that the SVM method is an effective tool in evaluating the risk of drugs when experimental M/P ratios have not been investigated.

Algorithms↗
PubMedDate not supplied

[Chronic lymphoid hemopathies in adults: chronic lymphocytic leukaemia and the phase of dissemination of small cell lymphomas].

Chronic lymphocytic leukaemia is the most frequent haematological cancer in adult patients, and its incidence raises with aging. Diagnosis needs several clinical and biological data, but hemogram together with the morphological and immunophenotypic analysis of the lymphoid cells take the major place. If the diagnosis is performed easily in about 65% of the patients, various clinicobiological entities were reported in the past few years that must be identified, at least because some are of adverse prognosis. Moreover, the other chronic lymphoid neoplasms, corresponding to the various low and intermediate grade non-Hodgkin's lymphomas (mainly of follicular type, marginal zone, mantle cell zone), may disseminate within the blood and the bone marrow. Those circulating lymphoma cells must be identified at diagnosis in order to perform the accurate diagnosis and to avoid an erroneous diagnosis of atypical chronic lymphocytic leukaemia. Up to 90% of lymphoid malignancies are B cell disorders, contrasting with only a few cases of T cell origin: some of those latter cases cannot be neglected however, as they may be observed in Western countries. Most recent classifications (REAL and WHO) defined all hematological malignancies: each entity referred to clinical, morphological, immunological, cytogenetic, and molecular findings. The basis of these classifications is pathophysiological, trying in each disorder to define a normal counterpart to the pathological clone. Reviewing main steps of the immune response in the normal patient, corresponding to those involving B cells, it is possible indeed to localize and demonstrate a function for many of the cells that expand in lymphoid malignancies.

Adult↗
PubMed2001

The mycobacteria: an introduction to nomenclature and pathogenesis.

Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance.

Animals↗
PubMed1994

[Development of molecular biomarkers for the detection of nonbiocompatible substances in the environment].

Many difficult issues confront toxicologists. For instance, animal studies have proved to be difficult for the assessment of human toxicity especially to measure directly the impact of low doses of toxic compounds. Recently, novel molecular approaches to cellular mechanisms involved in the response of "toxic stress" has broaden the field of toxicology. Indeed, the development of biological markers capable of detecting exposure to toxicants before a full-blown toxic response is an important current focus of environmental research. Cells from various organisms respond rapidly to toxic stress by altering their metabolic rates, cell growth or gene transcription controlling basic functions. Examples included are oxidative stress conveyed by peroxisomes, stress proteins implicated in protein folding and in detoxification and/or resistance. A number of potential practical applications of the stress response and stress proteins can be envisioned. Stress gene expression may be considered as a potential "biomonitor" to assess whether cells or organisms are experiencing metabolic stress within their environment. Such biological indicators should provide an early, sensitive, readily and measurable response for monitoring the actions of pollutants. In addition, the development of molecular and cellular probes may lead to new classification schemes for toxic compounds based upon various cellular and molecular responses rather than on toxicant structure.

Biomarkers↗
PubMed2005

[Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy].

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have resulted in the delineation of a treatment that has become a model of targeted therapy in oncology. GISTs are defined as tumors of the gastrointestinal tract, but also of the mesentery and peritoneum, constituted by a proliferation of usually spindle-shaped, rarely epithelioid cells, usually, but not consistently expressing the KIT protein. Most GISTs are associated with molecular abnormalities in two target genes: KIT (which encodes the KIT protein) and PDGFRA (which encodes the A chain of the PDGF receptor). The diagnosis of GIST relies on histological arguments (proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%; histological variants are rare and sometimes misleading) and on immunohistochemical arguments (expression of KIT in 95%, usually associated with CD34 expression in 60%-70% of cases). The demonstration of mutations in target genes is required only in cases that are histologically suggestive but KIT-negative; beyond this indication, this is only undertaken in research protocols. The differential diagnosis of GIST includes the other mesenchymal tumors of the gastrointestinal tract, such as leiomyomas and leiomyosarcomas, and the digestive locations of some sarcomas; it relies on both histological and immunohistochemical arguments. The evaluation of the prognosis is essential. According to the current concept, every GIST carries a risk of malignancy, which may vary from very low to very high. Prognosis is based on a simple algorithm using two histoprognostic parameters, i.e., tumor size and mitotic index. The treatment of localized GIST is surgical resection, which must be complete; that of advanced or unresectable GIST is based on the use of a targeted therapy, imatinib, which is a pharmacological antagonist of the KIT protein. Proper understanding and utilisation of the diagnostic criteria and classification of GIST by pathologists are essential for good patient management.

Adult↗
PubMed2006

Evaluating support for the current classification of eukaryotic diversity.

Perspectives on the classification of eukaryotic diversity have changed rapidly in recent years, as the four eukaryotic groups within the five-kingdom classification--plants, animals, fungi, and protists--have been transformed through numerous permutations into the current system of six "supergroups." The intent of the supergroup classification system is to unite microbial and macroscopic eukaryotes based on phylogenetic inference. This supergroup approach is increasing in popularity in the literature and is appearing in introductory biology textbooks. We evaluate the stability and support for the current six-supergroup classification of eukaryotes based on molecular genealogies. We assess three aspects of each supergroup: (1) the stability of its taxonomy, (2) the support for monophyly (single evolutionary origin) in molecular analyses targeting a supergroup, and (3) the support for monophyly when a supergroup is included as an out-group in phylogenetic studies targeting other taxa. Our analysis demonstrates that supergroup taxonomies are unstable and that support for groups varies tremendously, indicating that the current classification scheme of eukaryotes is likely premature. We highlight several trends contributing to the instability and discuss the requirements for establishing robust clades within the eukaryotic tree of life.

Animals↗
PubMed1996

The molecular pathology of small round-cell tumours--relevance to diagnosis, prognosis, and classification.

Substantial improvements have been made in the treatment and survival of children with SRCT, resulting in an increased emphasis on precise histological diagnosis. Although diagnostic procedures such as electron microscopy and immunocytochemistry contribute in poorly differentiated cases, an accurate diagnosis can remain elusive in a proportion of SRCTs. The cytogenetic and molecular genetic abnormalities characteristic of the different SRCTs can now be consistently and rapidly identified from minimal quantities of tumour material, using the techniques of FISH and PCR. This, coupled with the identification of novel phenotypic characteristics, has had a major impact on SRCT diagnosis. The aim of a tumour classification is to identify disease entities which are biologically distinct and whose recognition is of clinical value. The recent advances described above demonstrate that the SRCTs are genotypically and phenotypically distinct tumour types and that the genetic abnormalities represent key alterations that influence both the morphology and the clinical behaviour of the tumour. This suggests that these advanced phenotypic and genotypic analyses should form an integral and complementary part of the laboratory assessment and clinical management of these forms of paediatric cancer.

Bone Neoplasms↗
PubMed1991

Molecular and evolutionary relationships among enteric bacteria.

Classification of bacterial species into genera has traditionally relied upon variation in phenotypic characteristics. However, these phenotypes often have a multifactorial genetic basis, making unambiguous taxonomic placement of new species difficult. By designing evolutionarily conserved oligonucleotide primers, it is possible to amplify homologous regions of genes in diverse taxa using the polymerase chain reaction and determine their nucleotide sequences. We have constructed a phylogeny of some enteric bacteria, including five species classified as members of the genus Escherichia, based on nucleotide sequence variation at the loci encoding glyceraldehyde-3-phosphate dehydrogenase and outer membrane protein 3A, and compared this genealogy with the relationships inferred by biotyping. The DNA sequences of these genes defined congruent and robust phylogenetic trees indicating that they are an accurate reflection of the evolutionary history of the bacterial species. The five species of Escherichia were found to be distantly related and, contrary to their placement in the same genus, do not form a monophyletic group. These data provide a framework which allows the relationships of additional species of enteric bacteria to be inferred. These procedures have general applicability for analysis of the classification, evolution, and epidemiology of bacterial taxa.

Bacterial Outer Membrane Proteins↗
PubMed2001

Radiologic classification of malformations of cortical development.

Malformations of cerebral cortical development are common birth defects that can cause delayed development, epilepsy, focal neurologic deficits, and mental retardation. Rational classification of these disorders is essential for proper prognosis, genetic testing and counseling, and investigation of the underlying molecular causes. A rational approach to this classification is a framework based on whether these disorders are the result of abnormal cell proliferation or apoptosis, abnormal migration of immature neurons, or abnormal horizontal and radial orientation in the cortex. Superimposed on this framework are subclassifications that are based on topology of the malformation, associated central nervous system (CNS) or extra-CNS malformations, and results of molecular genetic testing. Characteristics that correlate with and enforce this system of classification can be identified by modern neuroimaging studies.

Animals↗
PubMed2005

Molecular diagnosis of inheritable neuromuscular disorders. Part II: Application of genetic testing in neuromuscular disease.

Molecular genetic advances have led to refinements in the classification of inherited neuromuscular disease, and to methods of molecular testing useful for diagnosis and management of selected patients. Testing should be performed as targeted studies, sometimes sequentially, but not as wasteful panels of multiple genetic tests performed simultaneously. Accurate diagnosis through molecular testing is available for the vast majority of patients with inherited neuropathies, resulting from mutations in three genes (PMP22, MPZ, and GJB1); the most common types of muscular dystrophies (Duchenne and Becker, facioscapulohumeral, and myotonic dystrophies); the inherited motor neuron disorders (spinal muscular atrophy, Kennedy's disease, and SOD1 related amyotrophic lateral sclerosis); and many other neuromuscular disorders. The role of potential multiple genetic influences on the development of acquired neuromuscular diseases is an increasingly active area of research.

Humans↗
PubMed2005

Movement disorders: classifications.

Movement disorders (ataxia, dystonic disorders, gait disorders, Huntington disease, myoclonus, parkinsonism, spasticity, tardive dyskinesia, tics and tremor) are clinically, pathologically and genetically heterogeneous and are characterized by impairment of the planning, control or execution of movement. Current classifications of these disorders have inherent shortcomings due to the complex nature of movement disorders and the lack of diagnostic tests for the majority. Undiscriminating terminology, as well as the clinical, pathological and genetic heterogeneity, further complicate the development of comprehensive categorizations. Modern classification schemes tend to focus on clinical, pathological or genetic/molecular criteria, but more recent attempts have been made to integrate across these levels. From a historical perspective, two 'golden ages' have shaped the current and evolving classification schemes: (1) the definition of clinical pathological entities in the early twentieth century and (2) the application of molecular neurogenetics in the past 10-15 years. However, the classification of movement disorders on clinical grounds (according to age at onset, distribution of symptoms, disease course, provoking factors and therapeutic response) remains one of the most useful modes of categorization. Postmortem criteria have been employed to distinguish between degenerative and nondegenerative disorders, and specific hallmarks may be required to establish or confirm a diagnosis. Genetic features used for classification purposes include mode of inheritance and molecular genetic data, such as linkage to a known gene locus or identification of a specific genetic defect. A final classification scheme is based on alterations in molecular mechanisms (e.g. trinucleotide expansions) or protein function (e.g. channelopathies). Despite recent advances, it may not be possible to develop the 'ultimate' classification of movement disorders, and different patterns of lumping and splitting may be useful for the clinician, the pathologist or the geneticist/molecular biologist. Furthermore, certain individual cases with unique features may not fit into any particular category. Continued research by both clinicians and basic scientists is necessary in order to refine and redefine classification schemes of movement disorders.

Dystonia↗
PubMed2004

[Kidney tumors in childhood].

Types of renal tumors arising in children are different from those occurring in adults. Nephroblastoma is the most common (85%) with a clinical outcome which has dramatically improved in the last 30 years. Current classifications are aimed at better adaptation of treatment to each individual case, reducing iatrogenic complications without impairing total cure. Amongst entities which have been recently described or are better known we can find juvenile carcinoma associated with Xp11.2 translocation, renal medullary carcinoma, metanephric tumors, etc. Role of molecular cytogenetics is increasing for classification (and treatment) and this should always be kept in mind when dealing a fresh specimen of childhood renal tumor.

Adult↗