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PubMed1993

Molecular evolution of P450 superfamily and P450-containing monooxygenase systems.

This paper reviews the classification of the P450 superfamily which is mainly based on sequence homology. The widely accepted classification by Nebert et al. [(1991) DNA Cell Biol. 10, 1-14] as well as the results of a 'two-step' multiple sequence alignment technique show that the molecular evolution of P450s, in contrast to that of many protein families, does not follow phylogeny. The data suggest that during the evolution of P450s, gene duplications and gene fusions, horizontal gene transfer and intron loss events have occurred. 'Weak' and 'strong' hierarchies in the clustering of P450 sequences were revealed. A novel evolutionary tree of the P450 superfamily has been constructed using a multiple alignment of consensus sequences. The simple classification of known P450-containing monooxygenase systems into three-, two- and one-component systems is further discussed. Particularly, the multidomain enzyme, nitric oxide synthase (NOS), should be classified as an example of a eukaryotic one-component P450 system since its N-terminal (haem) domain exhibits similarity with microsomal P450s.

Amino Acid Sequence↗
PubMed2005

Cytogenetic and molecular aspects of lung cancer.

Lung cancer is one of the most common cancers worldwide and its pathogenesis is closely associated with tobacco smoking. Continuous exposure of smoking carcinogens results in the accumulation of several alterations of tumorigenesis related genes leading to neoplastic bronchial lesions. Lung cancer is divided in two main histological groups, non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep process in which a number of genetic events including alterations of oncogenes and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung cancer are very complex. However, a number of recurrent cytogenetic abnormalities have been identified. Many of these changes are common in both major histological groups of lung cancer while certain chromosomal abnormalities have been correlated with the stage or the grade of the tumors. In addition, several molecular alterations have been constantly found. Some of them are common in different histological subtypes of lung cancer and they appear to play an important role in the pathogenesis of lung cancer. A good understanding of the underlying genetic changes of lung tumorigenesis will provide new perspectives for early diagnosis and screening of high-risk individuals. In addition, a number of genetical prognostic factors have been identified as possibly helpful parameters in the evaluation of lung cancer patients. Further research is required in order to systematically investigate genetical alterations in lung cancer contributing to improvement of lung cancer classification and staging and to development of new molecular targeted therapies.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

Paediatric embryonic brain tumours. biological and clinical relevance of molecular genetic abnormalities.

Embryonal tumours constitute the largest group of malignant paediatric brain tumours. Their origin and histological classification remain somewhat controversial. However, in recent years real progress has been made in our understanding of the molecular genetic abnormalities that govern the initiation and/or progression of these tumours. A number of these abnormalities appear to involve alterations in signalling systems that control normal cerebellar development. Increasing our understanding of both the biology and clinical relevance of these molecular defects is a major challenge to the field of paediatric neuro-oncology. However, it likely represents the only means by which we will advance the management of these tumours, significantly reducing disease-related morbidity and mortality. This review focuses on the principal molecular genetic abnormalities so far identified in embryonal brain tumours and discusses their biological and clinical relevance.

Brain Neoplasms↗
PubMed2000

Use of conventional taxonomy, electrophoretic karyotyping and DNA-DNA hybridization for the classification of fermentative apiculate yeasts.

A taxonomic study was conducted that considered strains of the genera Hanseniaspora/Kloeckera held in the Industrial Yeasts Collection (DBVPG) of the Dipartimento di Biologia Vegetale of the Università di Perugia, Italy. Standard phenotypic as well as molecular criteria were considered in a effort to revisit the classification of these strains, some of which have been in the collection for about 50 years. Results of salient physiological tests showed that some of the DBVPG and type strains could not be identified by current taxonomic keys. Electrophoretic karyotypes were identical for some species, with the type strains of the seven accepted species showing only five distinct chromosomal patterns. DNA-DNA hybridization analyses, using a non-radioactive dot-blot technique, allowed for the distinction of taxa. The taxonomic implications of these results are discussed.

Chromosomes, Fungal↗
PubMed1996

Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization.

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of beta 4-integrin. The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as beta 4-integrin by its reaction with polyclonal and monoclonal antibodies to human beta 4-integrin. Sera from patients with bullous pemphigoid, pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding. These data strongly implicate a role for human beta 4-integrin in the pathogenesis of OCP. It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases. Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of cicatricial pemphigoid and help distinguishing them from bullous pemphigoid. This study highlights the function and importance of beta 4-integrin in maintaining the attachment of epithelial cells to the basement membrane.

Amino Acid Sequence↗
PubMed2003

Nodal marginal zone B-cell lymphoma with a novel t(X;5)(q28;q22): conventional and molecular cytogenetic analysis.

Cytogenetic studies provide important information for the diagnosis and classification of malignant lymphomas that in some cases also has prognostic significance. Furthermore, the investigation of isolated novel cytogenetic findings in malignant lymphoma has led to the discovery of many important oncogenes and tumor suppressor genes. For this reason, a case of nodal marginal zone B-cell lymphoma in a 72-year-old woman is described in which analysis by conventional and molecular cytogenetic techniques demonstrated the presence of a t(X:5)(q28;q22) as the sole chromosomal abnormality. This translocation has not been previously reported in the literature.

Aged↗
PubMed2003

Reflections on the classification of yeasts for different end-users in biotechnology, ecology, and medicine.

The approach to yeast identification has significantly changed in just a few decades due to the rapid increase in basic biological knowledge, increased interest in the practical applications and biodiversity of this important microbial group, and enormous technological advances. While some conventional methods can still be validly applied, many molecular techniques have been developed that allow for strain classification on all taxonomic levels. A critical evaluation of the actual scope of each identification procedure will in the end determine the most appropriate use of the many protocols now available. Nonetheless, the oldest tool of microbiology, the microscope, is still a fundamental accessory for studies involving yeast biology, biodiversity and taxonomy.

Biotechnology↗
PubMed2005

Angioedema.

UNLABELLED: Although first described more than 130 years ago, the pathophysiology, origin, and management of the several types of angioedema are poorly understood by most dermatologists. Although clinically similar, angioedema can be caused by either mast cell degranulation or activation of kinin formation. In the former category, allergic and nonsteroidal anti-inflammatory drug-induced angioedema are frequently accompanied by urticaria. Idiopathic chronic angioedema is also usually accompanied by urticaria, but can occur without hives. In either case, an autoimmune process leading to dermal mast cell degranulation occurs in some patients. In these patients, histamine-releasing IgG anti-FcepsilonR1 autoantibodies are believed to be the cause of the disease, removal or suppression by immunomodulation being followed by remission. Angiotensin-converting enzyme inhibitor-induced angioedema is unaccompanied by hives, and is caused by the inhibition of enzymatic degradation of tissue bradykinin. Hereditary angioedema, caused by unchecked tissue bradykinin formation, is recognized biochemically by a low plasma C'4 and low quantitative or functional C'1 inhibitor. Progress has now been made in understanding the molecular genetic basis of the two isoforms of this dominantly inherited disease. Recently, a third type of hereditary angioedema has been defined by several groups. Occurring exclusively in women, it is not associated with detectable abnormalities of the complement system. Angioedema caused by a C'1 esterase inhibitor deficiency can also be acquired in several clinical settings, including lymphoma and autoimmune connective tissue disease. It can also occur as a consequence of specific anti-C'1 esterase autoantibodies in some patients. We have reviewed the clinical features, diagnosis, and management of these different subtypes of angioedema. LEARNING OBJECTIVE: After completing this learning activity, participants should be aware of the classification, causes, and differential diagnosis of angioedema, the molecular basis of hereditary and non-hereditary forms of angioedema, and be able to formulate a pathophysiology-based treatment strategy for each of the subtypes of angioedema.

Acute Disease↗
PubMed1989

Molecular spectroscopy in forensic residue analysis: a general overview of reliability, applicability and cost effectiveness.

Classification of an analytical result for forensic purposes is briefly discussed, in addition to mandatory specificity and limits of appropriate analytical methods. Direct information on the molecular structure of the analyte is in general more reliable than indirect information. Direct information is obtained from molecular spectroscopic methods, in contrasts to chromatographic or immunochemical methods, which provide only indirect information. The cost effectiveness ratio as calculated per analyte is indicated for various analytical techniques.

Animals↗
PubMed2001

Translocations involving anaplastic lymphoma kinase (ALK).

Anaplastic large-cell lymphoma (ALCL) comprises a group of non-Hodgkin's lymphomas (NHLs) that were first described in 1985 by Stein and co-workers and are characterized by the expression of the CD30/Ki-1 antigen (Stein et al., 1985). Approximately half of these lymphomas are associated with a typical chromosomal translocation, t(2;5)(p23;q35). Much confusion about the exact classification and clinicopathological features of this subgroup of NHL was clarified with the identification of NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) as the oncogene created by the t(2;5) (Morris et al., 1994). With the discovery of NPM-ALK as the specific lymphoma gene mutation, this NHL subtype could be redefined on the molecular level. This achievement was enhanced by the availability of specific antibodies that recognize ALK fusion proteins in paraffin-embedded lymphoma tissues. Several excellent recent reviews have summarized the histopathological and molecular findings of ALCL and their use in the classification of this lymphoma entity (Anagnostopoulos and Stein, 2000; Benharroch et al., 1998; Drexler et al., 2000; Foss et al., 2000; Gogusev and Nezelof, 1998; Kadin and Morris, 1998; Ladanyi, 1997; Morris et al., 2001; Shiota and Mori, 1996; Skinnider et al., 1999; Stein et al., 2000). This review will focus on the molecular function and signal transduction pathways activated by ALK fusion oncogenes, with recent advances and possible clinical implications to be discussed.

Amino Acid Sequence↗
PubMedDate not supplied

[Highest level of division in the organism classification. 1. Prokaryotes and eukaryotes].

The works on the general classification of all organisms are considered as a convenient opportunity to sum up numerous data obtained in organic world studying. The present stage is characterized by rapid development of the molecular reconstructions that have already caused considerable changes in our classification practice. These changes look especially impressive at studying the organism cellular structure. The great massive of new data allow us to compare Prokaryotes and Eukaryotes on the nucleic acids and especially proteins whose number in Eukaryote cell approaches to several thousands. Basing on the structure of macromolecules one can hypothesize with great certainty about Prokaryote or Eukaryotes origin. The article presents the detailed characteristic of Prokaryotes or Eukaryotes with the emphasis placed on the comparative analysis of biological macromolecules. Among specially considered cellular structures and processes are cell wall, intracellular components, cellular cycle, nucleus, DNA compactness, replication, genome organization, transcription, posttranscriptional modifications, introns, ribosomes and translation, cytoskeleton, mitosis, cytokinesis, cellular organelles, intracellular membranes systems, modes of nutrition, sexual condition. The macromolecular analysis let to carry out the homology of structures and to find out some new connections. It was shown that typology considered as a search for morphological patterns within the biodiversity structure has almost exhausted the subject. It was directed mostly to distinguishing "main" group in contrast with intermediate and aberrant ones, which were considered as minor phenomenon. At present due to macromolecules systematics it is able to estimate the whole diversity of forms including typologically transitive.

Biodiversity↗
PubMed1989

Molecular characterization of the human beta 3-adrenergic receptor.

Since the classification of beta-adrenergic receptors (beta-ARs) into beta 1 and beta 2 subtypes, additional beta-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third beta-AR, here referred to as the "beta 3-adrenergic receptor." Exposure of eukaryotic cells transfected with this gene to adrenaline or noradrenaline promotes the accumulation of adenosine 3',5'-monophosphate; only 2 of 11 classical beta-AR blockers efficiently inhibited this effect, whereas two others behaved as beta 3-AR agonists. The potency order of beta-AR agonists for the beta 3-AR correlates with their rank order for stimulating various metabolic processes in tissues where atypical adrenergic sites are thought to exist. In particular, novel beta-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the beta 3-AR.

Adrenergic beta-Agonists↗
PubMed2000

Progress in the classification of hematological neoplasms. From REAL to WHO concept

Recent advances in immunology, molecular biology and cytogenetics as well as the development of new diagnostic techniques set out the necessity for the redefinition and reclassification of hematological malignancies. Therefore, WHO in 1995 assigned the Society of Hematopathology and European Association for Hematopathology to create a new classification of these neoplasms. The result of collaborative efforts of leading hematopathologists from both organizations is the World Health Organisation (WHO) classification of hematological neoplasms. WHO classification adopted basic concepts, defined criteria introduced by REAL classification of lymphoid neoplasms and extended them to myeloid, histiocytic and mastocytic neoplasms. WHO classification of hematological neoplasms is represented by a list of disease entities and its variants, opened for inclusion of new entities, updating of diagnostic criteria and changes of nomenclature. The clinical relevance of the proposed entities has been evaluated by the clinicians, members of Clinical Advisory Committee. The proposed classification is a challenge to the clinicians to create new treatment strategy, directed towards particular disease entities. The presentation of WHO classification in our review is limited to myeloid and lymphoid neoplasms.

Journal Article↗
PubMed2006

Statistical analysis of DNA microarray data in cancer research.

Microarray techniques have been widely used to monitor gene expression in many areas of biomedical research. They have been widely used for tumor diagnosis and classification, prediction of prognoses and treatment, and understanding of molecular mechanisms, biochemical pathways, and gene networks. Statistical methods are vital for these scientific endeavors. This article reviews recent developments of statistical methods for analyzing data from microarray experiments. Emphasis has been given to normalization of expression from multiple arrays, selecting significantly differentially expressed genes, tumor classifications, and gene expression pathways and networks.

Cluster Analysis↗
PubMed1996

Clinical and cytofunctional classification of pituitary adenomas: proposal of a new classification.

Recent methodological advances in immunohistochemistry, ultrastructural techniques, hormonal assays, resolution imaging and molecular biology techniques have provided new insights into the pathology, function and cytogenesis of pituitary adenomas. Pituitary adenomas have been classified historically on the basis of tinctorial affinities, followed by the basis of ultrastructure and immunohistochemistry. The current development of technologies necessitate the new classification of pituitary adenomas which integrates these numerous parameters as well as the clinical manifestations. For this purpose, we suggest a new clinico-cytofunctional classification of pituitary adenomas, which is based on these clinical manifestations and integrates the information on biology, imaging function and ultrastructure. This classification which corresponds to current advances will not only provide pertinent clinical data but facilitate better understanding of the biology and nature of these complexed lesions.

Adenoma↗
PubMed2006

Classification of atherosclerotic rabbit aorta samples with an infrared attenuated total reflection catheter and multivariate data analysis.

The strongly overlapping infrared absorption features of atherosclerotic and normal rabbit aorta samples as governed by their water, lipid, and protein content render the direct evaluation of molecular characteristics obtained from infrared (IR) spectroscopic measurements challenging for classification. We have successfully applied multivariate data analysis and classification techniques based on partial least squares regression (PLS), linear discriminant analysis (LDA), and principal component regression (PCR) to IR spectroscopic data obtained by using a recently developed infrared attenuated total reflectance (IR-ATR) catheter prototype for future in vivo diagnostic applications. Training data were collected ex vivo from atherosclerotic and normal rabbit aorta samples. The successful classification results on atherosclerotic and normal aorta samples utilizing the developed data evaluation routines reveals the potential of spectroscopy combined with multivariate classification strategies for the identification of normal and atherosclerotic aorta tissue for in vitro and, in the future, in vivo applications.

Algorithms↗
PubMed1997

Molecular genetics is revolutionizing our understanding of ophthalmic disease.

PURPOSE: To inform ophthalmologists of the extraordinary progress in molecular genetics that is revolutionizing our understanding of ophthalmic disease and of the crucial role of the clinician in facilitating genetic discovery. METHOD: Review of relevant articles. RESULTS: Genes for many mendelian-inherited eye diseases have been localized and some identified using three general approaches: positional cloning, which requires no knowledge of underlying pathophysiology; a candidate gene approach, which examines genes based on their likely function; and a positional candidate approach, which uses map location as well as candidate genes in the linked region to isolate a gene. In positional cloning, once linkage is obtained, the gene can eventually be isolated, cloned, and sequenced and mutations identified. Techniques in molecular biology and other disciplines can then be used to unravel the pathophysiology of a disease. CONCLUSIONS: Molecular genetics is advancing our understanding of the classification and pathophysiology of ophthalmic diseases. The present classification system, based largely on clinical description of disease, is being replaced with a more rational classification based on genetic causes. Future research will determine the function of known genes and identify susceptibility loci for complex diseases such as chronic open-angle glaucoma and age-related macular degeneration. More specific diagnostic, therapeutic, and preventive strategies for ophthalmic disease will be developed. Clinicians play a crucial role by inquiring about the family history of all patients, identifying individuals and families with a genetic trait, and, when appropriate, referring them for further investigation.

Chromosome Mapping↗
PubMed2003

Primary brain tumours in adults.

The most frequent primary brain tumours in adults are gliomas and primary CNS lymphomas. In gliomas, molecular genetic analysis plays an increasing part in classification and treatment planning, a feature well illustrated by the chemosensitive oligodendrogliomas. Unfortunately, management of glioblastoma is still mainly palliative. Incidence of primary CNS lymphoma has increased strikingly in the past 20 years; substantial progress has been achieved in patients who are immunocompetent with the addition of methotrexate-based chemotherapy to radiotherapy, but the potential neurotoxic effects of this combination in elderly patients is worrisome.

Adult↗