Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Molecular Classification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources
PubMed2003

Pathologic and molecular aspects of soft tissue sarcomas.

This article retains the conventional approach to the classification of soft tissue sarcomas, dividing them into several major histogenetic categories based on their overall microscopic appearance, tissue differentiation pattern, and biologic potential. The author advocates a multimodal approach, in which four distinctive data sets--clinical, radiographic, microscopic, and, in some cases, molecular--are considered to establish the diagnosis and treatment plan. Such step-wise analysis is more likely to lead to consistency and accuracy as compared with an intuitive approach based on fragmentary data. The author describes individual lesions of soft tissue as clinicopathologic entities and believes that they can be more accurately diagnosed and appropriately treated with the help of data generated by a multidisciplinary team. In addition, this article emphasizes the need to use emerging molecular techniques that can provide important clues for both diagnosis and prognosis.

Clinical Trials as Topic↗
PubMed2006

Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease.

To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM1 patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2.

14-3-3 Proteins↗
PubMed1996

FGFR2 mutation in clinically nonclassifiable autosomal dominant craniosynostosis with pronounced phenotypic variation.

We describe a mutation in the FGFR2 gene in affected members of a large family with inherited autosomal dominant craniosynostosis. The mutation is a G1044A transition at codon 344 of exon B of the gene and results in abnormal splicing of the FGFR2 transcript. The phenotypic effect of the mutation varies greatly. It ranges from minor anomalies such as slight hypertelorism and maxillary hypoplasia to severe manifestations such as brachycephaly and dolichocephaly. The severe cases required surgery because of increased intracranial pressure. The patients cannot be assigned clinically to one of the known craniosynostotic syndromes with mutations in FGFR2, e.g., Crouzon, Pfeiffer, or Jackson-Weiss. This study demonstrates that FGFR2 mutations can result in a spectrum of craniofacial abnormalities even within one family. The known eponymic syndromes of Crouzon, Pfeiffer, or Jackson-Weiss only describe phenotypic extremes of this spectrum. Therefore, the clinical classification should be abandoned and replaced by a molecular one such as "FGFR-associated craniosynostosis syndromes."

Adolescent↗
PubMed1995

Childhood cancer.

BACKGROUND: Cancers of individual organs generally are composed of various histologic types, each with its own frequency and demographic patterns. For childhood cancers in particular, a classification of cancers by histologic type is important for understanding the etiology and progression of the disease. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Program on 9308 microscopically confirmed malignant neoplasms in children younger than age 15, newly diagnosed during 1973-1987, were made available for analysis. Tumors were grouped histologically according to a classification previously utilized in an international volume of childhood cancer incidence. RESULTS: The most frequent histologic types were acute lymphocytic leukemia (23.6%), astrocytoma (9.6%), neuroblastoma (6.6%), and Wilms' tumor (6.4%). Acute lymphocytic leukemia accounted for 75% of childhood leukemia. The most common form of Hodgkin's disease was the nodular sclerosing subtype, which was diagnosed in 56% of all cases. Burkitt's and Burkitt-like disease accounted for approximately one third of non-Hodgkin's lymphoma, the sex ratio (male to female) being unusually high (5.7). Among the brain tumors, glioma was of interest because 198 cases (excluded from this analysis) were diagnosed without histologic confirmation--due, no doubt, to their inaccessibility for biopsy because they were located in the brain stem. The most common histologic type of soft tissue sarcoma was rhabdomyosarcoma, which accounted for 51% of the total, more than half of which were of the embryonal type. To the authors' knowledge, this report offers for the first time the relative frequencies of rare types of leukemias, such as megakaryoblastic leukemia, in childhood. This report also includes the frequencies of 21 rarer forms of soft tissue sarcoma. Five forms of childhood cancer had a 5-year relative survival rate of 85% or better. Of the cancers with the poorest outcome, three had relative survival rates of 46.5-49%; the relative survival rate of acute myelogenous leukemia was only 26.4%. The trends in survival over time for 21 types of childhood cancer also are included in this report. CONCLUSIONS: Further refinements in classification now are available through laboratory techniques utilizing molecular biology, immunology, and cytogenetics, which are of importance in etiologic studies, diagnosis, treatment, and prognosis. It would be important in the future for cancer registries to record the results of relevant laboratory tests for further analysis by subtype.

Adolescent↗
PubMed1999

A quadratic discriminant analysis of protein structure classification based on the Helix/Strand content.

Based on the 210 non-homologous proteins (domains) classified manually by Michie et al. (J. Mol. Biol. 262, 168-185, 1996), a new structure classification criterion of globular proteins relying on the content of helix/strand has been proposed, using a quadratic discriminant method. Each protein is classified into one of the three classes, i.e. those of alpha class, beta class and alphabeta class (including alpha/beta and alpha+beta classes). According to the new structure classification criterion, of the 210 proteins in the training set, 207 are correctly classified and thus the accuracy is 207/210=98.57%. Multiple cross-validation tests are performed. The jackknife test shows that of the 210 proteins 207 are correctly classified with an accuracy of 98.57%. To test the method further, of 3577 proteins (domains) extracted from SCOP, 91.39% of them are correctly reclassified by the new classification criterion. On average, the accuracy of the new criterion is about 8 percentage points higher than that of the criterion proposed by Nakashima et al. (J. Biochem. 99, 153-162, 1986). Our result shows that the classification based solely on structures is basically consistent with that combining both structural and evolutionary information. Further complete automated classification scheme should consider both structures and evolutionary relationship. The methodology presented provides an appropriate mathematical format to reach this goal.

Animals↗
PubMed2000

Testing morphological concepts of orders of pleurocarpous mosses (Bryophyta) using phylogenetic reconstructions based on TRNL-TRNF and RPS4 sequences.

The ordinal classification of pleurocarpous mosses rests on characters such as branching mode and architecture of the peristome teeth that line the mouth of the capsule. The Leucodontales comprise mainly epiphytic taxa, characterized by sympodial branching and reduced peristomes, whereas the Hypnales are primarily terricolous and monopodially branching. The third order, the Hookeriales, is defined by a unique architecture of the endostome. We sampled 78 exemplar taxa representing most families of these orders and sequenced two chloroplast loci, the trnL-trnF region and the rps4 gene, to test the monophyly and relationships of these orders of pleurocarpous mosses. Estimates of levels of saturation suggest that the trnL-trnF spacer and the third codon position of the rps4 gene have reached saturation, in at least the transitions. Analyses of the combined data set were performed under three optimality criteria with different sets of assumptions, such as excluding hypervariable positions, downweighting the most likely transformations, and indirect weighting of rps4 codon positions by including amino acid translations. Multiple parallelism in nonsynonymous mutations led to little or no improvement in various indices upon inclusion of amino acid sequences. Trees obtained under likelihood were significantly better under likelihood than the trees derived from the same matrix under parsimony. Our phylogenetic analyses suggest that (1) the pleurocarpous mosses, with the exception of the Cyrtopodaceae, form a monophyletic group which is here given formal recognition as the Hypnidae; (2) the Leucodontales are at least paraphyletic; and (3) the Hypnales form, with most members of the Leucodontalean grade, a monophyletic group sister to a Hookerialean lineage. The Hypopterygiaceae, Hookeriales, and a clade composed of Neorutenbergia, Pseudocryphaea, and Trachyloma likely represent a basal clade or grade within the Hypnidae. These results suggest that mode of branching and reduced peristomes are homoplastic at the ordinal level in pleurocarpous mosses.

Base Sequence↗
PubMed2000

The molecular basis of persistent hyperinsulinemic hypoglycemia of infancy and its pathologic substrates.

Recent advances in molecular genetics have established a molecular basis for persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and resulted in the identification of a number of well-defined genetic defects. On the basis of the available information on the molecular changes so far described, an attempt has been made to classify PHHI patients according to their genotype and phenotype, with reference to molecular genetics, pancreatic pathology and clinical appearance. This classification has resulted in the differentiation of three groups of PHHI patients, two with diffuse beta cell hyperfunction and one with focal beta cell hyperfunction.

Female↗
PubMed2006

Gastric Burkitt lymphoma is a distinct subtype that has superior outcomes to other types of Burkitt lymphoma/leukemia.

Burkitt lymphoma/leukemia (BL) is a highly aggressive non-Hodgkin's lymphoma (NHL) often presenting in extranodal sites or as an acute leukemia. Because of the shared molecular and genetic features, the World Health Organization classification of lymphoid diseases recognizes the lymphomatous and leukemic phases of BL as a single entity: a mature B cell neoplasm, subtype Burkitt lymphoma/Burkitt cell leukemia. Because BL frequently appears in the stomach, we investigated the clinical presentation and outcome of gastric BL. We discovered 21 patients with gastric BL through a survey of our NHL registry, and retrospectively analyzed the distinct features of BL, including the St Jude/Murphy staging, other extranodal involvement, morphology and immunophenotype, response to treatment, and clinical outcome. The patients' median age was 48 years (range, 7-75), and the male-to-female ratio was 2.5. Stage 1 was found in five patients, stage 2 in five patients, and stage 4 in 11 patients. The stomach body and antrum were most frequently involved. All 21 patients were treated with systemic intensive chemotherapy, producing a 71% (15/21) rate of complete response (CR) to chemotherapy. Both the 2-year disease-free and overall survival rates were 55%. All ten patients in BL stages 1 and 2 showed outstanding outcomes, and nine of the ten patients exhibited CR and long-term survival. These data show that a high proportion of patients with gastric BL have a localized disease that is limited to stage 1 and 2, and that these localized BLs have outstanding outcomes. These findings suggest that these BLs could represent a distinct subtype that might have a different biology, which needs to be defined.

Adolescent↗
PubMed1999

Spinocerebellar ataxias in Spanish patients: genetic analysis of familial and sporadic cases. The Ataxia Study Group.

Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. Five spinocerebellar ataxia genes (SCA1, SCA2, SCA3, SCA6 and SCA7) and another related dominant ataxia gene (DRPLA) have been cloned, allowing the genetic classification of these disorders. We present here the molecular analysis of 87 unrelated familial and 60 sporadic Spanish cases of spinocerebellar ataxia. For ADCA cases 15% were SCA2, 15% SCA3, 6% SCA1, 3% SCA7, 1% SCA6 and 1% DRPLA, an extremely rare mutation in Caucasoid populations. About 58% of ADCA cases remained genetically unclassified. All the SCA1 cases belong to the same geographical area and share a common haplotype for the SCA1 mutation. The expanded alleles ranged from 41 to 59 repeats for SCA1, 35 to 46 [corrected] for SCA2, 67 to 77 for SCA3, and 38 to 113 for SCA7. One SCA6 case had 25 repeats and one DRPLA case had 63 repeats. The highest CAG repeat variation in meiotic transmission of expanded alleles was detected in SCA7, this being of +67 units in one paternal transmission and giving rise to a 113 CAG repeat allele in a patient who died at 3 years of age. Meiotic transmissions have also shown a tendency to more frequent paternal transmission of expanded alleles in SCA1 and maternal in SCA7. All SCA1 and SCA2 expanded alleles analyzed consisted of pure CAG repeats, whereas normal alleles were interrupted by 1-2 CAT trinucleotides in SCA1, except for three alleles of 6, 14 and 21 CAG repeats, and by 1-3 CAA trinucleotides in SCA2. No SCA or DRPLA mutations were detected in the 60 sporadic cases of spinocerebellar ataxia, but one late onset patient was identified as a recessive form due to GAA-repeat expansions in the Friedreich's ataxia gene.

Adult↗
PubMed1989

Conformation of beta-hairpins in protein structures. A systematic classification with applications to modelling by homology, electron density fitting and protein engineering.

A systematic classification of beta-hairpin structures which takes into account the polypeptide chain length and hydrogen bonding between the two antiparallel beta-strands is described. We have used this classification of beta-hairpin structures and their specific sequence pattern to derive rules which demonstrate its usefulness in assisting modelling beta-hairpins. These rules can be applied to comparative model building, modelling into electron density and in the prediction of conformation of beta-hairpins to aid protein engineering.

Aspartic Acid Endopeptidases↗
PubMed1994

Cytogenetics in acute myeloid leukaemia.

A wealth of literature spanning 20 years describing cytogenetic abnormalities in acute myeloid leukaemia (AML) already exists. It ranges from single case reports of unusual abnormalities to large multicentre studies of hundreds of cases. A landmark publication was the Fourth International Workshop on Chromosomes in Acute Leukaemia which established a base line for diagnosis, prognosis and frequency of chromosome abnormalities in AML. Two large sources of information are a book, 'The Chromosomes in Human Cancer and Leukemia' and a catalogue of chromosome abnormalities, which aims to list all chromosome abnormalities described in the scientific and medical literature from 1973, when the widespread use of banding techniques, enabled the precise definition of the chromosome breakpoints. In this review the common cytogenetic abnormalities seen in AML with reference to associations with the French-American-British (FAB) classification, their possible prognostic significance and their associated molecular biology are summarized.

Acute Disease↗
PubMed1996

The genetics of idiopathic generalized epilepsy: implications for the understanding of its aetiology.

Epilepsy is one of the most common neurological disorders. Both inherited and acquired factors contribute to its multifactorial pathogenesis. A genetic predisposition plays a major role in the aetiology of the common idiopathic generalized epilepsies. Susceptibility genes for two syndromes of idiopathic generalized epilepsies, the benign familial neonatal convulsions and juvenile myoclonic epilepsy, have been assigned to the chromosomal regions 20q13 (EBN1), 8q24 (EBN2) and 6p21 (EJM1). Positional cloning of the mutations causing these traits will help to elucidate the molecular pathways of epileptogenesis and will imply a classification on a neurobiological basis. Insights into the underlying impairment of neuronal excitability should provide new concepts for the development of rational treatment strategies.

Animals↗
PubMed2006

The neuronal ceroid-lipofuscinoses: from past to present.

The neuronal ceroid-lipofuscinoses (NCLs) are inherited lysosomal storage diseases and constitute the most common group of children's progressive encephalopathies. Most childhood forms of NCL are clinically characterized by progressive loss of vision as well as mental and motor deterioration, epileptic seizures, and premature death, while the rare adult forms are dominated by dementia. All forms of NCL share common pathomorphological features. Autofluorescent, periodic acid-Schiff- and Sudan black B-positive granules, resistant to lipid solvents, accumulate in the cytoplasm of most nerve cells, and there is progressive and remarkably selective neuronal degeneration and loss. For a long time, the NCLs were grouped under the heading of the "amaurotic family idiocies" and conceived as lipidoses. However, in the late 1980s and 1990s the NCL storage cytosomes were shown to consist largely of two hydrophobic proteins: either subunit c of mitochondrial ATP synthase or sphingolipid activator proteins A and D. Since 1995 numerous mutations in at least seven different genes have been shown to underlie the multiple human and animal forms of NCL. This review discusses the historical evolution of the NCL concept and the impact of the recent biochemical and molecular genetic findings on our views on the classification and pathogenesis of these devastating brain disorders.

Cerebellar Cortex↗
PubMed2006

Whatever happened to "neonatal hepatitis"?

'Idiopathic neonatal hepatitis' is a term that has traditionally been used to denote a clinical syndrome manifest by prolonged jaundice in the neonate. This description is now used much less frequently because recent studies unite well-defined clinical, biochemical and molecular features of intrahepatic cholestasis into specific syndromes. Advances in the understanding of the molecular basis of cholestatic syndromes now enable the classification of syndromes based on biology and offer an opportunity to develop new diagnostic approaches and treatment strategies that take into account the genetic make-up of the child with cholestasis.

Bile↗
PubMedDate not supplied

Palmoplantar keratodermas.

The palmoplantar skin is a highly specialized tissue which is able to resist mechanical trauma and other physical stress. In recent years the more descriptive classification of keratodermas has switched to an exact molecular genetic view where gene functions are considered. Palmoplantar keratodermas can be separated in the following functional subgroups: disturbed gene fuctions in structural proteins (keratins), cornified envelope (loricrin, transglutaminase), cohesion (plakophilin, desmoplakin, desmoglein1), cell-to-cell communication (connexins), and transmembrane signal transduction (cathepsin C). This review intends to emphasize the typical clinical aspects and symptom complexes associated with palmoplantar keratodermas which enable the astute dermatologist to make a clinical diagnosis. In addition the molecular genetic knowledge on the topic is given which is necessary to confirm the clinical diagnosis.

Biopsy, Needle↗
PubMed2006

A new parasite that infects eggs of the mud crab, Scylla serrata, in Australia.

The mud crab, Scylla serrata, is currently being evaluated for its feasibility for mass aquaculture in Australia. As part of the evaluation process, pathogens that can affect this species need to be identified. This research note describes a possible new parasite that infects the eggs of S. serrata. The parasite was discovered in two separate cases (three months apart) in a broodstock research program and appears to cause 100% egg mortality. The parasite consists of a cluster of cells with rhizoids that appear to function as an anchorage and a feeding organ. The individual cells range from 3 to 6 microm with a single nucleus. The parasite could not be classified to a phylum by morphology alone. However, BLAST analysis of the DNA sequence from a PCR amplicon generated using universal 18S ribosomal RNA gene primers indicated similarity to pathogenic thraustochytrids, Dermocystidium sp. and Rhinosporidium seeberi. All except R. seeberi are protistan parasites of fish and crustaceans. A neighbour-joining phylogenetic tree confirmed the homology with the thraustochytrids; however, further molecular techniques need to be exploited for absolute classification of this new parasite.

Animals↗
PubMed2006

RhoA protein expression correlates positively with degree of malignancy in astrocytomas.

Astrocytic tumors are the most common intracranial neoplasms. Their prognoses correlate with a conventional morphological grading system that suffers from diagnostic subjectivity and hence, inter-observer inconsistency. A molecular marker that provides an objective reference for classification and prognostication of astrocytic tumors would be useful in diagnostic pathology. RhoA, a GTPase protein involved in cell migration and adhesion, has been shown to be upregulated in a variety of human cancers. Based on direct analysis of clinical materials, our study demonstrates increased expression of RhoA in high-grade astrocytomas. This observation may be relevant to astrocytoma biology and the development of potential therapeutics against high-grade astrocytomas. Of more immediate consequence, utilization of this marker may aid in the routine pathological grading (and hence prognostication) of astrocytomas.

Adolescent↗