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PubMed1994

[Microphthalmos and its pathogenic classification].

Congenital microphthalmos is a common malformation encountered clinically. Microphthalmos in adults is here defined as eyes whose axial length is below 20.4 mm in males and 20.1 mm in females; in under 14-year-old children, it is eyes at least 3 square root of 2/3 below the mean for age-similar controls. Experimental animals with hereditary microphthalmos have been widely investigated, and many environmental factors given to pregnant animals frequently induce microphthalmos. In both clinical and experimental microphthalmos, there are conspicuous variations in size, and various kinds of ocular and systemic complications. Recently, fetal alcohol syndrome produced by alcohol intake during pregnancy has been reported. In this syndrome, microphthalmos is one of the important symptoms. Experimentally, microphthalmos also developed at a high incidence among mouse fetuses whose mothers were given ethanol during pregnancy. The present investigator established a preliminary etiological classification of microphthalmos in 1984. In this paper summing up newly obtained results, the relationship to neural crest cells and histochemical changes of glycosaminoglycan molecular species, the author presents a final pathogenic classification of microphthalmos, which consists of developmental disturbance of the optic vesicle, malformation of the optic cup, mesenchymal dysgenesis of the anterior ocular segment, maldevelopment of the lens, maldevelopment of the vitreous, faulty closure of the embryonic fissure and developmental disturbance of the wall of eyeball.

Adolescent↗
PubMed2004

The value of fluorescence in situ hybridization and polymerase chain reaction in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration.

CONTEXT: Molecular genetic analyses have been predicted to improve the diagnostic accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma. OBJECTIVE: To determine the value of routine molecular genetic assays, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA). DESIGN: A multiparametric method, including cytology, flow cytometry, PCR, and FISH, was prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA. Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies were collected. All aspirates were triaged through a uniform program including cell-size analysis, B- and T-cell clonality studies, flow cytometric immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After completion of FNA evaluations, FNA results were compared with diagnoses from prior or subsequent surgical biopsies. RESULTS: Monoclonal B-cell populations were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR. bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma. bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular lymphomas and 1 transformed follicular lymphoma. By incorporating the results of molecular genetic and ancillary diagnostics, a definitive classification was reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma (4/8). Ten of the 12 cases with a final classification reached by FNA had either prior or follow-up surgical biopsies, and all 10 cases showed agreement between the diagnoses rendered on FNA and surgical biopsies. CONCLUSIONS: With proper handling and management of specimens, FNA can routinely provide samples adequate for molecular genetic studies, in addition to cytomorphology and flow cytometry, making it possible to consistently render accurate and definitive diagnoses in a subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods, FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin lymphoma.

Adult↗
PubMed1993

[Proposition of a new classification of the phylum of the protozoa Ciliophora Doflein, 1901].

It is proposed to use all the presently available molecular, ultrastructural, biological and ecological data on ciliates for the new classification of this group of protists. On the basis of the cortical organization and the mode of cilia anchoring as well as the degree of conservation of the cortical pattern during the process of morphogenesis, eleven classes (Karyorelictea, Heterotrichea, Hypotrichea, Oligotrichea, Plagiopylea, Colpodea, Litostomatea, Vestibuliferea, Phyllopharyngea, Nassophorea and Oligohymenophorea) have been distinguished. These classes, in turn, were, according to the "shell theory" of Fleury and coworkers (1992), grouped into three subphyla: Tubulicorticata (presence of the cortical microtubular lattices), Filicorticata (characteristic ecto-endoplasmic microfibrillar boundary) and Epiplasmata (presence of a sub-membraneous epiplasmic layer).

Animals↗
PubMed2005

Sesquiterpene lactone-based classification of three Asteraceae tribes: a study based on self-organizing neural networks applied to chemosystematics.

This work describes an application of artificial neural networks on a small data set of sesquiterpene lactones (STLs) of three tribes of the family Asteraceae. Structurally different types of representative STLs from seven subtribes of the tribes Eupatorieae, Heliantheae and Vernonieae were selected as input data for self-organizing neural networks. Encoding the 3D molecular structures of STLs and their projection onto Kohonen maps allowed the classification of Asteraceae into tribes and subtribes. This approach allowed the evaluation of structural similarities among different sets of 3D structures of sesquiterpene lactones and their correlation with the current taxonomic classification of the family. Predictions of the occurrence of STLs from a plant species according to the taxa they belong to were also performed by the networks. The methodology used in this work can be applied to chemosystematic or chemotaxonomic studies of Asteraceae.

Asteraceae↗
PubMed2006

The many faces of protein-protein interactions: A compendium of interface geometry.

A systematic classification of protein-protein interfaces is a valuable resource for understanding the principles of molecular recognition and for modelling protein complexes. Here, we present a classification of domain interfaces according to their geometry. Our new algorithm uses a hybrid approach of both sequential and structural features. The accuracy is evaluated on a hand-curated dataset of 416 interfaces. Our hybrid procedure achieves 83% precision and 95% recall, which improves the earlier sequence-based method by 5% on both terms. We classify virtually all domain interfaces of known structure, which results in nearly 6,000 distinct types of interfaces. In 40% of the cases, the interacting domain families associate in multiple orientations, suggesting that all the possible binding orientations need to be explored for modelling multidomain proteins and protein complexes. In general, hub proteins are shown to use distinct surface regions (multiple faces) for interactions with different partners. Our classification provides a convenient framework to query genuine gene fusion, which conserves binding orientation in both fused and separate forms. The result suggests that the binding orientations are not conserved in at least one-third of the gene fusion cases detected by a conventional sequence similarity search. We show that any evolutionary analysis on interfaces can be skewed by multiple binding orientations and multiple interaction partners. The taxonomic distribution of interface types suggests that ancient interfaces common to the three major kingdoms of life are enriched by symmetric homodimers. The classification results are online at http://www.scoppi.org.

Amino Acid Sequence↗
PubMed1994

[Androgen receptor and insensitivity to androgens].

Androgen insensitivity syndromes are suspected in XY subjects with normal testosterone secretion presenting with absent or severely impaired androgen dependent sexual differentiation. Such clinical features suggest an abnormality of the androgen receptor, necessary step in the transmission of the hormonal message. The androgen receptor is a member of the steroid/thyroid nuclear receptors superfamily. It is a soluble protein of 919 amino acids, divided in independent functional domains responsible for the various functions of the receptor:hormone and DNA binding, and transcriptional activation. The highest concentration of androgen receptor is found, in both sexes, in tissues resulting from primary or secondary sexual differentiation. Cloning of the androgen receptor and use of molecular biology techniques have led to a new classification of androgen insensitivity syndromes. In complete forms (complete androgen insensitivity:CAI) the phenotype is feminine. In receptor negative CAI (Rc-: complete loss of hormone binding), molecular abnormalities include rare, partial or complete, deletions of the gene, or, more frequently, single point mutations in the hormone binding domain, leading to a functionally inactive receptor. Identification and characterization of these mutations provide valuable information regarding the functional importance of specific amino acids of the androgen receptor. In receptor positive CAI (RC+: conserved hormone binding capacity), abnormalities have been reported in the DNA binding domain (deletion of a zinc finger, single point mutations), but also in the hormone binding domain, thus distinguishing between the hormone binding activity and the transcriptional activation activity of this domain. Partial insensitivity syndromes are characterized by an ambiguous and extremely variable phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed2006

PML-RARalpha fusion gene transcripts and biological features in acute promyelocytic leukemia patients.

Acute promyelocytic leukemia (APL) is characterized by the presence of rearrangements involving the retinoic acid receptor alpha (RARalpha) gene and a variable incidence in different populations. The hybrid gene PML-RARalpha, present in 98% of cases, encodes a fusion protein essential to the pathogenesis of the disease. Depending of the PML's gene breakpoint in chromosome 15, the transcript subtypes bcr1, bcr2 and bcr3 may be formed. The correlation between these transcript subtypes and clinical parameters is still controversial. The objective of this study was to determine the frequencies of the PML-RARalpha transcripts and subtypes in a series of 32 APL patients from Northeast Brazil and to evaluate the association of these subtypes to different parameters. The method used was RT-PCR. The frequency of our APL cases is approximately 28% of the acute leukemias. The results showed the presence of PML-RARalpha isoform in all patients and a higher frequency of the bcr1/2 subtype. No significant statistical association was found between molecular subtypes and age, sex, French-American-British (FAB) classification, leukocyte and platelet count, hemoglobin level or coagulation tests. In conclusion, these data suggest similar molecular and biological features for our APL patients at diagnosis in comparison with those reported in current scientific literature.

Adolescent↗
PubMed1999

Primary thymic epithelial neoplasms: spectrum of differentiation and histological features.

Primary thymic epithelial neoplasms have been the source of much controversy over the years because of difficulties in their histopathologic classification and prognostication of clinical behavior. Despite recent advances in our understanding of the immunopathology and molecular pathology of these neoplasms, no universally accepted system of classification is yet available for these tumors. A variety of classification schemes have been proposed in the past based on either morphological, histogenetic, or immunophenotypic considerations. For the most part, the majority of such classifications have been merely descriptive with little value for prognostication, or have proven cumbersome and difficult to apply in clinical practice. Recent studies have shown that primary thymic epithelial neoplasms, rather than representing several discrete, separate entities constitute part of a continuous spectrum of differentiation ranging from well-differentiated neoplasms to poorly-differentiated neoplasms. Based on these observations, a novel classification of primary thymic epithelial neoplasms has been proposed that divides these tumors into three easily reproducible diagnostic categories based on their degrees of differentiation: thymoma, atypical thymoma, and thymic carcinoma (corresponding to well-differentiated, moderately-differentiated, and poorly-differentiated neoplasms, respectively). The histopathologic features and diagnostic criteria for these tumors is the subject of this review.

Cell Differentiation↗
PubMed1986

Nature and classification of viruses affecting small animals.

The classification of animal viruses is predicated upon the various parameters discussed herein and the molecular biology of viruses. Although many of the parameters used for classification purposes have little obvious relation to the disease the veterinarian observes, it is necessary to utilize this information collectively to understand viral classification and its relationship to disease pathogenesis, treatment, diagnosis, and prevention because all these are predicted on the classification of animal viruses (Table 2).

Animals↗
PubMed1992

Pathology of malignant lymphomas.

Although the subject is now seldom formally addressed, much of the pathologic research into malignant lymphoma is still tacitly directed at developing a rational and reproducible classification. Pure morphology, while remaining of critical importance in the diagnosis of malignant lymphomas, has been exhausted as a means of understanding the biology of these tumors, which must be the eventual basis of a firm, enduring and clinically relevant classification. Thus, histopathologists have turned first to immunohistochemistry and now to molecular genetics to make sense of their morphologic observations. Correlation of various genetic (including oncogenetic) rearrangements with morphology has preoccupied pathologists this past year and has led to important advances in the understanding of B- and T-cell lymphomas. Lymphomas occurring in a setting of immunodeficiency, whether therapeutically induced or acquired, have received special attention, and the possible role of the Epstein-Barr virus in their pathogenesis has induced pathologists to develop exciting in situ molecular hybridization techniques for its identification in tissues. The certainties underlying the diagnosis and classification of Hodgkin's disease (in which Epstein-Barr virus also appears to play a role), formally the only truly secure area for pathologists, have been disturbed, and the borderline between Hodgkin's disease and non-Hodgkin's lymphoma is now seriously blurred. The lymphoma pot has been well and truly stirred; we must now wait to see what the new sediment offers.

Humans↗
PubMed1999

Peptides with antimicrobial activity of the brevinin-1 family isolated from skin secretions of the southern leopard frog, Rana sphenocephala.

Three peptides with growth-inhibitory activity towards the gram-negative bacterium Eschericia coli were isolated from electrically stimulated secretions from the skin of the southern leopard frog, Rana sphenocephala. Structural characterization demonstrated that the peptides [brevinin-1Sa, minimum inhibitory concentration (MIC) = 55 microM; brevinin-1Sb, MIC = 17 microM; brevinin-1Sc, MIC = 14 microM] represent new members of the brevinin-1 family of antimicrobial peptides, previously isolated from several other species of frogs of the genus Rana. Their high concentration in skin secretions and extreme variability in amino acid sequence suggest that the brevinin family of peptides may be of value as molecular markers for the identification and taxonomic classification of Ranid frogs.

Amino Acid Sequence↗
PubMed2004

Nanopore cheminformatics.

A cheminformatics method is described for classification, and biophysical examination, of individual molecules. A novel molecular detector is used--one based on current blockade measurements through a nanometer-scale ion channel (alpha-hemolysin). Classification results are described for blockades caused by DNA molecules in the alpha-hemolysin nanopore detector, with signal analysis and pattern recognition performed using a combination of methods from bioinformatics and machine learning. Due to the size of the alpha-hemolysin protein channel, the blockade events report on one DNA molecule at a time, which enables a variety of reproducible, single-molecule biophysical experiments. To capture the full sensitivity of the nanopore detector's blockade signal, Hidden Markov Models (HMMs) were used with Expectation/Maximization for denoising and for associating a feature vector with the ionic current blockade of each captured DNA molecule. Support Vector Machines (SVMs) that employ novel kernel designs were then used as discriminators. With SVM training performed off-line, and economical HMM processing on-line, blockade classification was possible during capture. HMMs were also used in conjunction with a time-domain finite state automaton (off-line) for feature discovery and kinetics analysis. Analysis of the DNA data indicates a variety of binding (DNA-protein), fraying, and conformational shifts that are consistent with data obtained from thermodynamic analyses (melting curves), X-ray crystallography, and NMR studies. The software tools are designed for analysis of generic blockades in ionic channels, including those in other biological pore-forming toxins, other biological channels in general, and semiconductor-based channels.

Base Sequence↗
PubMed1999

Genome archeology leading to the characterization and classification of transport proteins.

In the study of transmembrane transport, molecular phylogeny provides a reliable guide to protein structure, catalytic and noncatalytic transport mechanisms, mode of energy coupling and substrate specificity. It also allows prediction of the evolutionary history of a transporter family, leading to estimations of its age, source, and route of appearance. Phylogenetic analyses, therefore, provide a rational basis for the characterization and classification of transporters. A universal classification system has been described, based on both function and phylogeny, which has been designed to be applicable to all currently recognized and yet-to-be discovered transport proteins found in living organisms on Earth.

Carrier Proteins↗
PubMed1997

Evolution of 28S ribosomal DNA in chaetognaths: duplicate genes and molecular phylogeny.

The chaetognaths are an extraordinarily homogeneous phylum of animals at the morphological level, with a bauplan that can be traced back to the Cambrian. Despite the attention of zoologists for over two centuries, there is little agreement on classification within the phylum. We have used a molecular biological approach to investigate the phylogeny of extant chaetognaths. A rapidly evolving expansion segment toward the 5' end of 28S ribosomal DNA (rDNA) was amplified using the polymerase chain reaction (PCR), cloned, and sequenced from 26 chaetognath samples representing 18 species. An unusual finding was the presence of two distinct classes of 28S rDNA gene in chaetognaths; our analyses suggest these arose by a gene (or gene cluster) duplication in a common ancestor of extant chaetognaths. The two classes of chaetognath 28S rDNA have been subject to different rates of molecular evolution; we present evidence that both are expressed and functional. In phylogenetic reconstructions, the two classes of 28S rDNA yield trees that root each other; these clearly demonstrate that the Aphragmophora and Phragmophora are natural groups. Within the Aphragmophora, we find good support for the groupings denoted Solidosagitta, Parasagitta, and Pseudosagitta. The relationships between several well-supported groups within the Aphragmophora are uncertain; we suggest this reflects rapid, recent radiation during chaetognath evolution.

Animals↗
PubMed1998

A robust molecular phylogeny of the Tricladida (Platyhelminthes: Seriata) with a discussion on morphological synapomorphies.

The suborder Tricladida (Platyhelminthes: Turbellaria, Seriata) comprises most well-known species of free-living flatworms. Four infraorders are recognized: (i) the Maricola (marine planarians); (ii) the Cavernicola (a group of primarily cavernicolan planarians); (iii) the Paludicola (freshwater planarians); and (iv) the Terricola (land planarians). The phylogenetic relationships among these infraorders have been analysed using morphological characters, but they remain uncertain. Here we analyse the phylogeny and classification of the Tricladida, with additional, independent, molecular data from complete sequences of 18S rDNA and 18S rRNA. We use maximum parsimony and neighbour-joining methods and the characterization of a unique gene duplication event involving the Terricola and the dugesiids to reconstruct the phylogeny. The results show that the Maricola is monophyletic and is the primitive sister group to the rest of the Tricladida (the Paludicola plus the Terricola). The Paludicola are paraphyletic since the Terricola and one paludicolan family, the Dugesiidae, share a more recent common ancestor than the dugesiids with other paludicolans (dendrocoelids and planariids). A reassessment of morphological evidence may confirm the apparent redundancy of the existing infraorders Paludicola and Terricola. In the meantime, we suggest replacing the Paludicola and Terricola with a new clade, the Continenticola, which comprises the families Dugesiidae, Planariidae, Dendrocoelidae and the Terricola.

Animals↗
PubMed2006

Structures and serology of the O-antigens of Proteus strains classified into serogroup O17 and former serogroup O35.

INTRODUCTION: Bacteria of the genus Proteus are facultative pathogens which commonly cause urinary tract infections. Based on the serological specificity of the O-chain polysaccharide of the lipopolysaccharide (O-polysaccharide, O-antigen), strains of P. mirabilis and P. vulgaris have been classified into 60 serogroups. Studies on the chemical structure and serological specificity of the O-antigens aim at the elucidation of the molecular basis and improvement of the serological classification of these bacteria. MATERIALS AND METHODS: The O-polysaccharide was prepared by acetic acid degradation of the lipopolysaccharide isolated from dried bacterial mass of each strain by hot phenol/water extraction. (1)H- and (13)C-NMR spectroscopy was used for structural studies. Serological studies were performed with rabbit O-antisera using enzyme immunosorbent assay, passive hemolysis test, and the inhibition of reactions in these assays as well DOC-PAGE and Western blot. RESULTS: Four Proteus strains belonging to serogroups O17 and O35 were found to possess similar O-polysaccharide structures, in particular having the same carbohydrate backbone built up of tetrasaccharide repeating units. However, they differ in the presence or absence of additional substituents, such as phosphoethanolamine in P. mirabilis O17 and glucose in P. penneri O17, as well as in the pattern and degree of O-acetylation of various monosaccharide residues. Serological studies also showed close relationships between the O-antigens studied. CONCLUSIONS: Based on these data it is proposed to reclassify strain P. mirabilis PrK 61/57, formerly representing the O35 serogroup, into the serogroup O17 in the Kauffman-Perch classification system of Proteus.

Carbohydrate Conformation↗
PubMed1996

The last revised "Euro-American classification" of lymphoid leukemias and non-Hodgkin's lymphomas: the same inaccuracies and inconsistencies in a chaotic complexity.

After a review of the recent physiologic, cellular genetic and molecular genetic acquisitions, a critical comment of the proposed classification is presented concerning especially a) the inclusion in the so-called "precursor B-lymphoblastic leukemias", which are pre-B neoplasias, of Burkitt's leukemic lymphoma, the cells of which are sIg+, hence B and not pre B; b) the inclusion in the chronic B lymphocytic leukemia of the so-called Galton's "prolymphocytic" leukemia, the cells of which are also sIg+, thus B and not pro B. In fact, the transformed blastoid medium size cells of this leukemia present the markers of the plasmablasts, which are the precursors of the long-lived plasma cells and migrate from the lymphoid tissue T-zone to bone marrow, where they secrete IgD, or G, or E, or to the mucosae, where they secrete IgA. Thus the so called "B-prolymphocytic leukemia" is the leukemic conversion of the (blastoid medium size cell) plasmablast lymphoma. There is in the new classification, a "large cell lymphoma" entity, which makes redundance with the "large cell follicle centre lymphoma". This large cell lymphoma representes a heterogen complex, as it includes the B-immunoblastic lymphoma which is not presented as an entity. As far as T lymphomas are concerned, it is not indicated that the CD8 cells may be CD57 + or - , and CD28 + or -. It could be mentioned that the cytotoxic T-cells are CD8+ C57- CD28+, while the suppressor T-cells are CD8+ CD57+ CD28-.

Humans↗
PubMed2003

Effect of external stresses on protein conformation: a computer modelling study.

The increasing use of digital technologies such as mobile phones has led to major health concerns about the effects of non-ionizing pulsed radiation exposure. We believe that the health implications of exposure to radiation cannot be fully understood without establishing the molecular mechanisms of biological effects of pulsed microwaves. We aim to establish methods for studying the molecular mechanisms of protein structural and energetic changes occurring due to external stresses related to non-ionizing radiation by using a combination of experimental and theoretical approaches. In this paper, we present the results from our fully atomistic simulation study of chemical and thermal stress response of a prototype protein, insulin. We performed a series of molecular dynamics simulations of insulin in solution under equilibrium conditions, under chemical stress (imitated by reducing the disulfide bonds in the protein molecule), and under short-lived thermal stress (imitated by increasing simulation temperature for up to 2 ns). The resultant protein conformational behaviour was analysed for various properties with the aim of establishing analysis routines for classification of protein unfolding pathways and associated molecular mechanisms.

Algorithms↗