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PubMed2005

Advances and trends in the molecular systematics of the parasitic Platyhelminthes.

The application of molecular systematics to the parasitic Platyhelminthes (Cestoda, Digenea and Monogenea) over the last decade has advanced our understanding of their interrelationships and evolution substantially. Here we review the current state of play and the early works that led to the molecular-based hypotheses that now predominate in the field; advances in their systematics, taxonomy, classification and phylogeny, as well as trends in species circumscription, molecular targets and analytical methods are discussed for each of the three major parasitic groups. A by-product of this effort has been an ever increasing number of parasitic flatworms characterized genetically, and the useful application of these data to the diagnosis of animal and human pathogens, and to the elucidation of life histories are presented. The final section considers future directions in the field, including taxon sampling, molecular targets of choice, and the current and future utility of mitochondrial and nuclear genomics in systematic study.

Animals↗
PubMedDate not supplied

Molecular evidence for the existence of two species of Marteilia in Europe.

Marteilia refringens is one of the most significant pathogens of bivalve molluscs. Previous sequencing of the small subunit ribosomal RNA gene of M. refringens isolates derived from the infected mussels (Mytilus edulis and Mytilus galloprovinciallis) and the oyster (Ostrea edulis) in Europe did not reveal genetic polymorphisms despite indications from epizootiological data that distinct types may exist. We investigated the existence of polymorphisms in the internal transcribed spacer region of the ribosomal RNA genes. The sequences of this region proved to be clearly dimorphic among Marteilia from five sampling sites. The distribution of the two genetic types, named "O" and "M", appeared to be linked to the host species, oysters and mussels, respectively. We therefore support the recognition of two species of Marteilia in Europe and propose that the "O" type corresponds to M. refringens and the "M" type to M. maurini.

Animals↗
PubMed1993

Bioamine receptors: evolutionary and functional variations of a structural leitmotiv.

Bioamines act as neurohormonal messengers through their binding to receptors which belong to the largest membrane protein family known so far: the seven spanning membrane receptors. This class of receptors transmits the effect of agonist binding to intracellular effectors by interacting with an intermediary G-protein. The diversity of receptor subtypes inside the protein family, observed in many animal species, is the result of a long evolutionary process. The tendency to protein diversification depends upon gene duplications and upon the continuous accumulation of mutations. The maintenance of vital functions in organisms, however, strictly requires enough structural conservation to ensure the functionality of the corresponding proteins. Both forces cooperate to ensure the adaptation of organisms to a changing environment. We have reviewed here the main conformational and functional constraints exerted on the structure of the bioamine receptors. They are mainly the transmembrane conformation of the receptors, their ability to bind ligands, to interact with G-proteins and to desensitize. The molecular basis of the biochemical and pharmacological differences used to classify the members of the receptor family have also been examined. Interestingly, this classification is very close to that obtained by the molecular phylogeny methods, used to elucidate the evolutionary relationships between bioamine receptors. However, this latter classification allows to accurately distinguish between different receptor subtypes (paralogous genes) and species homologous (orthologous genes). In addition, the calculation of phylogenetical distances reveals two main periods of diversification: the first one occurred before the separation of arthropods from vertebrates, in the Precambrian, and corresponds to the appearance of the main subtypes of the bioamine receptors. The second one, which occurred about 400 million years ago, might accompany the cephalization of the CNS in vertebrates.

Animals↗
PubMed2006

Molecular phylogeny of Hyphoderma and the reinstatement of Peniophorella.

Hyphoderma is a large genus of corticioid homobasidiomycetes. In earlier homobasidiomycete-wide molecular phylogenetic studies the genus has appeared as polyphyletic. This paper describes the results from phylogenetic analyses of 22 species of Hyphoderma using nuclear 5.8 S and 28 S rDNA. Species with echinocysts and stephanocysts form a distinct clade well separated from Hyphoderma s. str. For this group the old genus name Peniophorella is available with P. pubera as the type species. Nineteen new combinations in Peniophorella are made and a key to the species is given. The clade representing Hyphoderma in its restricted sense receives only indicative support and a further subdivision of the genus may become necessary. H. capitatum, H. orphanellum, and H. sibiricum belong neither to Peniophorella nor to Hyphoderma s. str. Hypochnicium is a sister group to Hyphoderma. The phylogenetic analyses support the segregation of Hypochnicium analogum and H. vellereum as Gloeohypochnicium analogum and Granulobasidium vellereum, respectively, and the inclusion of H. detriticum in Hyphodontia. Hyphodermopsis and Bulbillomyces are best regarded as synonyms of Hypochnicium.

Base Sequence↗
PubMed1998

Who's related to whom? Recent results from molecular systematic studies.

Similarities among model systems can lead to generalizations about plants, but understanding the differences requires systematic data. Molecular phylogenetic analyses produce results similar to traditional classifications in the grasses (Poaceae), and relationships among the cereal crops are quite clear. Chloroplast-based phylogenies for the Solanaceae show that tomato is best considered as a species of Solanum, closely related to potatoes. Traditional classifications in the Brassicaceae are misleading with regard to true phylogenetic relationships and data are only now beginning to clarify the situation. Molecular data are also being used to revise our view of relationships among flowering plant families. Phylogenetic data are critical for interpreting hypotheses of the evolution of development.

Evolution, Molecular↗
PubMedDate not supplied

Will the "new biology" affect the future of histopathology?

The technologies used in histopathology are changing as a consequence of the current revolutionary progress in several areas of biology. It is likely that general cancer management will improve because of the impact of molecular techniques and immunohistochemistry on tumor diagnosis and classification and on the determination of prognosis and response to therapy. Moreover, as therapies are starting to be modelled after the distinctive molecular characteristics of a specific tumor, the availability of molecular tests to all patients will become a matter of great importance.

Biomarkers, Tumor↗
PubMed1999

B-cell lymphoma of 708 cases in Japan: incidence rates and clinical prognosis according to the REAL classification.

New insights into the pathogenesis of lymphoid malignancies have been gained through novel techniques such as genetic, molecular and immunologic methods. Recently, based on those findings, a new classification system for lymphoid malignancies, known as the REAL classification, has been proposed. To clarify the relation between the histological classification and prognosis of B-cell lymphoid malignancies, we re-classified 708 cases. In all cases, the B-cell phenotype and/or genotype was confirmed by immunohistochemical staining and/or receptor gene analysis. The most common B-cell lymphoma types were diffuse large B-cell lymphoma (58.8%), follicular lymphoma (12.1%), marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (9.0%) and mantle cell lymphoma (5.9%). Minor types were lymphoblastic lymphoma (3.4%), Burkitt's lymphoma (2.4%), nodal marginal zone lymphoma (2.1%), lymphoplasmacytic lymphoma (2.0%) and plasmacytoma (1.4%). Rare types were prolymphocytic lymphoma and splenic marginal zone lymphoma. Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (1) the low risk group consisted of follicular lymphoma, marginal zone lymphoma of MALT, nodal marginal zone lymphoma, plasmacytoma and lymphoplasmacytic lymphoma; (2) the intermediate risk group consisted of diffuse large B-cell lymphoma, Burkitt's lymphoma and mantle cell lymphoma; and (3) the high risk group consisted of lymphoblastic lymphoma. In MALT, the low grade type had a better prognosis than the high grade type. In diffuse large B-cell lymphoma, the common type had a better prognosis than the variant type, which mainly consisted of the immunoblastic lymphoma. The histological classification will have a benefit for the clinical approach.

Adolescent↗
PubMedDate not supplied

Molecular pathogenesis of non-Hodgkin lymphoma: a clinical perspective.

Despite a common origin from mature lymphoid cells, non-Hodgkin lymphomas (NHL) represent a surprisingly heterogeneous group of lymphoid malignancies whose classification is continuously being remodeled. The most recent proposal, the Revised European-American classification, introduces pathogenetic features among the classification criteria. In this respect, knowledge of the molecular pathogenesis of NHL, which is based upon genetic lesions leading to activation of proto-oncogenes (e.g. BCL-1, BCL-2, BCL-6, c-MYC) or disruption of tumor suppressor genes (e.g. p53), is becoming increasingly relevant for the clinician. These lesions combine into multiple molecular pathways which are selectively associated with distinct NHL types. Thus, for example, rearrangements of BCL-1, BCL-2, BCL-6, and c-MYC ar the genetic hallmarks of mantle cell, follicular, diffuse large cell, and Burkitt's lymphoma, respectively. Overall, from clinical perspective, NHL genetic lesions serve three purposes: a) they assist and complement histologic diagnosis; b) they provide a molecular marker with prognostic relevance; c) they allow evaluation of minimal residual disease through highly specific and highly sensitive technologies.

Cell Transformation, Viral↗
PubMed2004

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

Adult↗
PubMed1997

The emergence of genetic coding in physical systems.

A simple model of molecular biological translation, based on the classification of polymers as either information carriers or functional catalysts, is used to analyse formal constraints on physical systems which utilise genetic coding. We investigate (i) how the structure-function relationship for coding assignment catalysts constrains the selection of genetic information which can sustain functional self-organisation and (ii) what general prerequisites must be satisfied for selection to give rise to an increase in functional complexity. This is done by considering two separate alphabets and defining the complete set of assignments from letters of one alphabet onto letters from the other. A code is defined as a set of assignments which maps each letter from the first alphabet onto a letter from the second alphabet. We enumerate all the embeddings of the assignment functions in the minimal sequence space of strings of letters from the second alphabet and demonstrate how the embeddings can be classified according to whether they allow different codes to be represented unambiguously in the minimal sequence space of strings of letters from the first alphabet. Non-minimal embeddings are also discussed. Finally, we consider how the mutual specification of letters of the two alphabets and assignment functions can be decomposed into more highly differentiated classes. Only a certain class of embeddings allows coding to be preserved under decomposition. We conclude that the evolution of increasing coding complexity can take place only when special conditions are satisfied regarding the structure-function relationship for the coding assignment catalysts.

Animals↗
PubMed1999

Coronary atherosclerosis and interventions: pathological sequences and restenosis.

The primary cause of cardiac morbidity and mortality in developed countries is ischemic (coronary) heart disease. The incidence of this disease is virtually all due to atherosclerosis, and ischemic heart disease is also the most prevalent disease in the industrialized world, causing over 40% of all deaths in the United States and Western Europe. In Japan, the incidence of ischemic heart disease due to coronary atherosclerosis is gradually increasing as well. Compared with the classical nomenclature of atherosclerosis; that is, fatty streak, fibrous plaque and complicated lesions, the term Stary's classification has been universally accepted because it reflects the more recently acquired knowledge about the morphological and biochemical details of the processes in coronary atherosclerosis, which have been obtained by new strategies such as angioscopy, intravascular ultrasound and molecular biological methods. The term Stary's classification has been applied for the coronary atherosclerosis of patients with acute coronary syndrome at the National Cardiovascular Center, for the analysis of predisposing atherosclerosis of these patients. The recent findings regarding acute coronary syndrome resulting from a rupture of coronary atherosclerotic plaques indicate that this syndrome is probably the most important mechanism underlying the sudden onset. It has been found that the risk of plaque rupture may depend more on plaque composition than on plaque size. Plaques rich in soft extracellular lipids and macrophages are possibly more vulnerable to plaque rupture. Two of the goals of the present review are to clarify how plaque disruption occurs and to elucidate the relationship between plaque disruption and coronary risk factors in elderly Japanese patients with acute coronary syndrome. Coronary stents have been shown to be efficacious in the treatment of acute and threatened closure complicating percutaneous transluminal coronary angioplasty (PTCA) and have produced encouraging initial results in the prevention of restenosis. In the autopsy study of restenosis after PTCA, it was observed that dense caps of collagen fibers in the adventitia in the vicinity of the disrupted internal elastic laminae were present in all of the remodeling lesions. It is suggested that remodeling, which resulted in adventitial scarring, is one of the major causative factors of restenosis after PTCA. The long-term success of stenting, however, remains limited by the occurrence of late in-stent restenosis, with an incidence of 20-42% depending on the stent design and the patient population studied. Another aim of the present review is to describe the pathological mechanism of restenosis after PTCA and/or stent replacement and, consequently, the vascular remodeling that occurs around adventitial tissue after PTCA and intimal hyperplasia that is chronically irritated by a foreign body granulomatous reaction after stenting. Finally, the results of the investigation of the effect of a tissue factor pathway inhibitor on the prevention of interventional restenosis is described.

Angioplasty, Balloon, Coronary↗
PubMed2005

Molecular phylogeny, recent radiation and evolution of gross morphology of the rhubarb genus Rheum (Polygonaceae) inferred from chloroplast DNA trnL-F sequences.

BACKGROUND AND AIMS: Rheum, a highly diversified genus with about 60 species, is mainly confined to the mountainous and desert regions of the Qinghai-Tibetan plateau and adjacent areas. This genus represents a good example of the extensive diversification of the temperate genera in the Qinghai-Tibetan plateau, in which the forces to drive diversification remain unknown. To date, the infrageneric classification of Rheum has been mainly based on morphological characters. However, it may have been subject to convergent evolution under habitat pressure, and the systematic position of some sections are unclear, especially Sect. Globulosa, which has globular inflorescences, and Sect. Nobilia, which has semi-translucent bracts. Recent palynological research has found substantial contradictions between exine patterns and the current classification of Rheum. Two specific objectives of this research were (1) to evaluate possible relationships of some ambiguous sections with a unique morphology, and (2) to examine possible occurrence of the radiative speciation with low genetic divergence across the total genus and the correlation between the extensive diversification time of Rheum and past geographical events, especially the recent large-scale uplifts of the Qinghai-Tibetan Plateau. METHODS: The chloroplast DNA trnL-F region of 29 individuals representing 26 species of Rheum, belonging to seven out of eight sections, was sequenced and compared. The phylogenetic relationships were further constructed based on the sequences obtained. KEY RESULTS: Despite the highly diversified morphology, the genetic variation in this DNA fragment is relatively low. The molecular phylogeny is highly inconsistent with gross morphology, pollen exine patterns and traditional classifications, except for identifying all samples of Sect. Palmata, three species of Sect. Spiciformia and a few species of Sect. Rheum as corresponding monophyletic groups. The monotypic Sect. Globulosa showed a tentative position within the clade comprising five species of Sect. Rheum. All of the analyses revealed the paraphyly of R. nobile and R. alexandrae, the only two species of Sect. Nobilia circumscribed by the possession of large bracts. The crude calibration of lineages based on trnL-F sequence differentiation implied an extensive diversification of Rheum within approx. 7 million years. CONCLUSIONS: Based on these results, it is suggested that the rich geological and ecological diversity caused by the recent large-scale uplifts of the Qinghai-Tibetan Plateau since the late Tertiary, coupled with the oscillating climate of the Quaternary stage, might have promoted rapid speciation in small and isolated populations, as well as allowing the fixation of unique or rare morphological characters in Rheum. Such a rapid radiation, combined with introgressive hybridization and reticulate evolution, may have caused the transfer of cpDNA haplotypes between morphologically dissimilar species, and might account for the inconsistency between morphological classification and molecular phylogeny reported here.

Biological Evolution↗
PubMed1999

Phylogenetic classification and the universal tree.

From comparative analyses of the nucleotide sequences of genes encoding ribosomal RNAs and several proteins, molecular phylogeneticists have constructed a "universal tree of life," taking it as the basis for a "natural" hierarchical classification of all living things. Although confidence in some of the tree's early branches has recently been shaken, new approaches could still resolve many methodological uncertainties. More challenging is evidence that most archaeal and bacterial genomes (and the inferred ancestral eukaryotic nuclear genome) contain genes from multiple sources. If "chimerism" or "lateral gene transfer" cannot be dismissed as trivial in extent or limited to special categories of genes, then no hierarchical universal classification can be taken as natural. Molecular phylogeneticists will have failed to find the "true tree," not because their methods are inadequate or because they have chosen the wrong genes, but because the history of life cannot properly be represented as a tree. However, taxonomies based on molecular sequences will remain indispensable, and understanding of the evolutionary process will ultimately be enriched, not impoverished.

Animals↗
PubMed2004

Pathobiology, classification, and diagnosis of myelodysplastic syndrome.

Recent advances in molecular genetics have advanced the knowledge regarding the mechanisms leading to myelodysplastic syndrome (MDS), secondary acute myeloid leukemia, and therapy-induced MDS. Unfavorable cytogenetics associated with this group of disorders includes monosomy or deletion of the long arm of chromosomes 5 or 7, inversions of chromosome 3, translocations, deletions, and trisomies involving several other chromosomes. These unbalanced chromosomal aberrations result in hemizygosity and unmasking of oncogenes, changes in levels of expressed genes, or inactivation of tumor suppressor genes. It is evident that the cytogenetics associated with MDS is highly complex and heterogeneous, leading to an equally heterogeneous manifestation of the disease. Classifications, initially defined by the French-British-American group followed by the World Health Organization, and now by the International Prognostic Scoring System, have determined prognosis and helped develop treatment strategies for these patients, thus reducing their potential to develop acute leukemia. To date there are seven different prognostic schemas. These are constantly being improved so that MDS patients, who tend to be elderly, can be suitably treated. Additionally, treatment considerations and prognosis are different for patients who develop therapy-related MDS or for the juvenile population than for those with de novo MDS. The genetic alterations in MDS bone marrow and blood cells have been identified and possible models have been proposed for the development and progress of MDS, from the early stage to late-stage MDS evolving to acute myeloid leukaemia. As the functional mechanisms behind these chromosomal changes are being revealed, new therapies based on these mechanisms are currently being made and tested.

Apoptosis↗
PubMed1992

Molecular basis for Glanzmann's thrombasthenia (GT) in a compound heterozygote with glycoprotein IIb gene: a proposal for the classification of GT based on the biosynthetic pathway of glycoprotein IIb-IIIa complex.

The genetic basis for Glanzmann's thrombasthenia (GT) was elucidated on a compound heterozygote with glycoprotein (GP)IIb gene: an opal mutation at the end of exon 17 (CGA----TGA) results in only a trace amount of GPIIb mRNA, and a splicing mutation at the acceptor site of exon 26 (CAG----GAG) causes an in-frame, exon skipping process from exon 25 to 27. This aberrant transcript encodes a single-chain polypeptide characterized by a 42-amino acid deletion, which includes the proteolytic cleavage site(s) and a unique, proline-rich region at the location corresponding to the carboxyl-terminal of the normal GPIIb alpha-chain. These characteristics are shared by a previously reported defective GPIIb molecule, which is neither assembled with GPIIIa nor transported to the cellular surface. Despite its normal transcription level, expression of the present defective GPIIb molecule was significantly decreased (approximately 6% of the control level). Because the precursor GPIIb molecule is assembled with GPIIIa in the endoplasmic reticulum (ER) and its processing, as well as stability, is dependent on the GPIIIa subunit, the defective GPIIb molecule may be rapidly degraded by the intrinsic quality control system of the ER due to its inability to form a stable heterodimer complex as a consequence of its misfolded structure. Although we did not confirm that the GPIIIa genes of this individual were normal, GPIIIa may be secondarily decreased (approximately 11% of control), because a large part of it could not be complexed, making it vulnerable to proteolysis. To elucidate the molecular basis for GT, we propose here a classification of GT based on the biosynthetic pathway of the GPIIb-IIIa complex.

Base Sequence↗
PubMed1999

Classification of cutaneous malignant melanoma: a reassessment of histopathologic criteria for the distinction of different types.

BACKGROUND: Human cutaneous malignant melanoma currently is classified into four principle types: nodular, superficial spreading, lentigo maligna, and acral lentiginous. The criteria for the histopathologic diagnosis of these types are not applied consistently. Nevertheless, the classification has become the foundation of many clinical, histopathologic, epidemiologic, and molecular studies. The results of those studies can have validity only if the classification itself is valid. For this reason, the authors reassessed histopathologic criteria advocated for the distinction of the different types of melanoma and searched for other repeatable constellations of findings that may serve to define distinct subsets of the neoplasm. METHODS: Nine hundred fifteen melanomas were examined with regard to 72 parameters that are considered to be important for histopathologic diagnosis. The results were analyzed statistically with special attention to findings that have been reported to be characteristic of the four principle types of melanoma. RESULTS: The histopathologic criteria advocated for the distinction of different types of melanoma were found not to correlate with one another. A logistic regression analysis did not detect any other repeatable constellation of morphologic findings that may reflect a distinct biologic subgroup. CONCLUSIONS: The validity of the current classification of cutaneous malignant melanoma into four principle types could not be substantiated. Malignant melanoma may present with many different forms, but these forms appear to be part of a continuous spectrum rather than examples of distinct biologic entities.

Adult↗
PubMed2025

DNA Methylation-Based Classification of Kidney Neoplasms.

Renal neoplasms are morphologically and molecularly heterogeneous, with their diagnosis often hindered by interobserver variability and overlapping microscopic features. A subset of cases is unclassifiable despite immunohistochemical, mutation, and cytogenetic-based diagnostic workup. Through examination of the genome-wide DNA methylation signatures of over 2000 renal neoplasms, we identified 23 coherent groups that correlate with known neoplasm types and identified novel clinically relevant subtypes of existing neoplasm types. We used machine learning models to develop and validate a classifier trained on DNA methylation profiles of 1284 samples. The classifier was tested on an external data set of 287 renal neoplasms with >90% concordance between expected neoplasm type and high-score DNA methylation-based classification. Discordance between the original histologic label and methylation class led to potential reclassification of some cases. This work demonstrates proof of principle for the feasibility of a DNA methylation classifier as a clinically useful tool to assist in the diagnosis of renal neoplasms.

Humans↗
PubMed2001

Mapping of resistance to vegetable polyphenols among Aedes taxa (Diptera, Culicidae) on a molecular phylogeny.

To recover some evolutionary aspects of the interaction between culicine larvae and dietary polyphenols of the vegetation surrounding mosquito breeding sites, we constructed a phylogeny of the most common French Aedes species, chosen as reference species. We also evaluated the differential resistance of these larval taxa to the polyphenols of leaf litter from the riparian vegetation used as a food source. Mitochondrial DNA sequence analysis was performed among 14 different taxa and ecotypes (Aedes aegypti, Ae. albopictus, Ae. cantans, Ae. caspius, Ae. cataphylla, Ae. cinereus, Ae. detritus, Ae. geniculatus, Ae. mariae, Ae. pullatus, Ae. punctor, Ae. rusticus, Ae. sticticus, and Ae. vexans) through direct sequencing of a 763-base segment of the cytochrome oxidase subunit I gene. Phylogenetic analysis, based on nucleotide and amino acid sequences, was conducted by means of parsimony and distance methods. The differential tolerance of larvae to vegetable leaf litter was comparatively tested by use of 10-month-old alder leaf litter as an experimental standard. The absence of correlation between resistance to polyphenols and molecular phylogeny suggests that larval adaptation to polyphenol-rich vegetable breeding sites is a labile character. The acquisition of such resistance appears not to be ancestrally inherited, but rather to be a dynamic adaptation to the environment. Molecular data also support the classical morphological classification within the Aedes genus.

Aedes↗