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PubMed1994

[Evaluation of multiple prognostic factors in colorectal cancer].

A multivariate stepwise discriminant analysis was performed to evaluate the prognostic value of DI, PI, AgNOR, p21D, CEAD and several clinicopathological features (age, sex, tumor location, histological grading, typing and staging) in 83 patients with colorectal cancer who underwent radical surgery. A fisher's discriminant function was established by using 6 selected items (staging, grading, DI, PI, AgNOR and p21D). It's efficiency, sensitivity and specificity were 91.28%, 87.18%, and 95.45% respectively. Correlative studies on DI, PI, AgNOR and p21D indicated that they are independent factors influencing prognosis. Therefore, in addition to Dukes's classification and histopathological grading of the tumor, these molecular biological factors can be considered as a new clue to evaluation of patients prognosis.

Adult↗
PubMed1993

The current management of thyroid tumors in childhood.

Thyroid cancer is a rare but intriguing malignancy when it occurs in childhood and adolescence. Although it often presents at a more advanced stage than similar adult thyroid tumors, the biologic behavior is more benign, accounting for improved survival. Therefore, pediatricians and surgeons have debated the wisdom of aggressive versus conservative surgical approaches. Although the final answers have not been achieved it has become increasingly clear that radical surgical approaches may be unnecessary. Further investigation of the tumor cell biology, genetics, and molecular biology of thyroid tumors may allow prospective classification of children so that the best operative and adjuvant management can be selected for each individual.

Child↗
PubMed1993

Confirmation of the taxonomic position of Callimico goeldi (Primates, Platyrrhini) on the basis of its highly repeated DNA patterns.

The systematic position of Callimico goeldi has been analyzed by comparison of its highly repeated DNA fragments with those of three species of Callithricidae and two species of Cebidae. Our data, in agreement with those obtained by other authors by means of cytogenetic and molecular biology techniques, are in favour of the classification of C. goeldi in the family Callithricidae.

Animals↗
PubMed1997

[Dyscromic neurocutaneous syndromes].

Discromic neurocutaneous syndromes are an heterogeneous group of genetic diseases which associate pigmentary anomalies to nervous system disturbances. Development of molecular biology has allowed a better understanding and classification of this diseases. In this article we review this entities with an emphasis on the last clinical and genetic discoveries.

Angiofibroma↗
PubMed2006

Classification of sporadic Creutzfeldt-Jakob disease revisited.

The sporadic form of Creutzfeldt-Jakob disease (sCJD) has been classified on the basis of the molecular mass of the protease-resistant scrapie prion protein (PrP(Sc)), which can be type 1 or type 2, and the genotype at the methionine (M)/valine (V) polymorphic codon 129, which can be MM, MV or VV. In one classification proposed by 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: 224-33.] the most common subtype of sCJD, designated sCJDMM1, is viewed as a single entity. Two other classifications proposed by Collinge et al. [Collinge J, Sidle KC, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383: 685-90.] and Zanusso et al., [Zanusso G, Farinazzo A, Fiorini M, Gelati M, Castagna A, Righetti PG, Rizzuto N, Monaco S . pH-dependent prion protein conformation in classical Creutzfeldt-Jakob disease. J Biol Chem 2001; 276: 40377-80.] respectively, subdivide sCJDMM1 into two subtypes on the basis of the different molecular mass and phenotypic characteristics, primarily disease duration. To resolve this discrepancy, we divided a group of 22 subjects with confirmed sCJDMM1 according to Parchi et al. into two sub-populations according to whether the disease duration was <5 months (short-duration subjects) or >7 months (long-duration subjects). We then examined the PrP(Sc) molecular mass under the conditions that allowed wide variability of the pH of the PrP(Sc) preparations as well as under stringent pH conditions, using high-resolution gel electrophoresis. We also compared the characteristics of the PrP(Sc) associated with the short- and long-duration subjects using two-dimensional immunoblot, conformational stability immunoassay and sucrose gradient fractionation. Finally, the two sub-populations were also compared with regard to their clinical and pathological features including the lesion profiles. When sample homogenization and protease digestion were performed under stringent pH conditions, the PrP(Sc) molecular mass did not differ between short- and long-duration sCJDMM1 subjects. The conformational characteristics of the protease-resistant PrP(Sc) as well as the clinical and pathological phenotypes were also homogeneous except for the more severe lesions of the long-duration cases. We therefore conclude that the variability of the PrP(Sc) molecular mass underlying the division of sCJDMM1 into two subtypes is largely due to pH variations during tissue preparation, and sCJDMM1 with short and long disease duration have similar phenotypes and PrP(Sc) characteristics. These data indicate that the differentiation of sCJDMM1 into two subgroups is not currently justified.

Aged↗
PubMed1996

Molecular biology in ophthalmology. A review of principles and recent advances.

Molecular biology is a young scientific discipline that has already had a profound impact on biomedical science, including basic and clinical eye research. In the coming years, molecular advances will increasingly influence aspects of diagnosis, prognosis, and therapy in clinical ophthalmology. Our current understanding of ocular pathophysiology and classification of eye disease will be advanced and challenged by new discoveries in molecular biology. A knowledge of genotype can clarify apparent phenotype. At the present time, diagnostic tests in ophthalmology for both acquired and inherited diseases are being revolutionized by molecular technology. The molecular genetics of ocular disease is currently the subject of intense investigation using techniques of gene mapping and isolation. Rapid progress in understanding the molecular basis of eye diseases will advance the treatment of these conditions, including the potential for gene therapy.

Amino Acid Sequence↗
PubMed2001

A phylogeny of the land snails (Gastropoda: Pulmonata).

We have undertaken the first large-scale molecular phylogenetic analysis of the Stylommatophora. Sequences of the ribosomal RNA gene-cluster were examined in 104 species of snails and slugs from 50 families, encompassing all the currently recognized major groups. It allows an independent test of the present classification based on morphology. At the level of families our molecular phylogeny closely supports the current taxonomy, but the deep branches within the tree do not. Surprisingly, a single assemblage including the families Achatinidae, Subulinidae and Streptaxidae lies near the base of the tree, forming a sister group to all remaining stylommatophorans. This primary division into 'achatinoid' and 'non-achatinoid' taxa is unexpected, and demands a radical reinterpretation of early stylommatophoran evolution. In particular, the Orthurethra appear to be relatively advanced within the 'non-achatinoid clade', and broadly equivalent to other super-familial clusters. This indicates that supposedly primitive features such as the orthurethran kidney are derived. The molecular tree also suggests that the origin of the Stylommatophora is much earlier than the main period of their diversification.

Animals↗
PubMed1998

Molecular genetics of the hereditary ataxias.

One of us (MP) learned about the mapping of Huntington disease gene to chromosome 4 from the late Dr. Anita Harding. She got the news over the phone from her London office during a visit to Italy for a meeting on hereditary ataxias. In Britain, they receive Nature at least a week earlier than us. Dr. Harding was very excited, and she immediately said that that was the way to go if we wanted to understand the causes of hereditary ataxias, classify these diseases in a rational way, and eventually find a treatment. At that time, the challenge seemed, and indeed was, formidable. No clue was then available about the genetic basis of what Dr. Harding aptly called "hereditary ataxias of unknown cause," their classification was confused and controversial, and all attempts to find specific biochemical abnormalities had failed. Fourteen years later, the success of the molecular genetic studies is astounding. The defective genes have been identified for Friedreich ataxia, the major recessive "hereditary ataxia of unknown cause," and for five dominantly inherited "hereditary ataxias of unknown cause." Three more dominant ataxia genes have been mapped. The molecular pathogenesis of the dominant ataxias begins to be unraveled and animal models have been and are being developed. Information is also quickly accumulating about the defective protein in Friedreich ataxia. Direct molecular diagnosis is now possible. Classification has been revolutionized. Diagnostic criteria are being redefined in the light of the molecular discoveries. The goal of this review, dedicated to the memory of the late Dr. Harding, is to offer a concise summary of current knowledge about the molecular genetics of some of the hereditary ataxias that used to be classified as of "unknown cause."

Ataxia↗
PubMed2005

Study on the pathophysiologic basis of classification of 'spleen' deficiency in chronic gastritis.

BACKGROUND: Most of the studies on traditional Chinese medicine (TCM) 'spleen' deficiency syndrome in the recent 30 years were conducted only on the basis of single functional index, neglecting the study on the pathophysiologic internal relationship between spleen deficiency syndrome and gastric diseases in modern medicine. But it was at the subcellular molecular biological level that we explored the pathophysiologic basis of classification of spleen deficiency in chronic gastritis by detecting the bioactive substances in gastric mucosa nuclei and mitochondria. METHODS: By means of optical microscope, scanning electron microscope (SEM), transmission electron microscopy (TEM) and histochemical staining, we conducted histopathological, subcellular ultrastructural analysis and nuclei and mitochondrial ultrastructural analysis of gastric mucosa of 188 spleen deficiency patients and of 42 voluntary blood donors. At the same time, bioactive substances were measured by means of X-ray energy dispersive analysis system (EDAX) image analysis system, radioimmunoassay method and chemiluminescence method. RESULTS: The content of cAMP, superoxide dismutase (SOD), Zn and Cu in gastric mucosa, and the content of Zn and Cu in mitochondria decreased progressively in order of groups: healthy control (HC), spleen Qi deficiency without organic lesion (F-SQD), spleen Yang deficiency without organic lesion (F-SyangD), disease without symptoms group, spleen Qi deficiency with organic lesion (G-SQD), spleen Yang deficiency with organic lesion (G-SyangD), spleen Yin deficiency (SyinD) and spleen deficiency with Qi stagnation (SDQS), chronic spleen deficiency gastritis (CSG) and chronic atrophic gastritis (CAG); decreased in order of HC, intestinal metaplasia (IM)Ia, IMIb, IMIIa and IMIIb, P < 0.05. The content of DNA, Zn and Cu in nuclei progressively increased in order mentioned above, P < 0.05. CONCLUSIONS: The quantitative changes of gastric mucosal cAMP, SOD, Zn, Cu, of mitochondrial Zn, Cu and of nuclear DNA, Zn and Cu are not only the substance base on which the lesion of gastric mucosa tissue structure occurs, but also the substance base on which spleen deficiency is classified. G-SQD and G-SyangD were more likely to be found in low-grade or middle-grade CSG and CAG, while SyinD and SDQS in middle-grade or high-grade CSG, CAG and IMIIb.

Adult↗
PubMed2003

Microarrays: new tools for transplantation research.

The advent of DNA microarray technology has greatly enhanced our potential to understand the molecular basis of human diseases and to aid in more accurate classification, diagnosis and/or prognosis. This powerful, flexible and highly informative technique has been adopted by many biomedical research disciplines. The use of DNA microarrays for gene expression profiling of patients undergoing organ transplantation has diagnostic and therapeutic potential. By generating global views of the gene expression changes in renal graft function post transplantation, DNA microarray technology will provide important information to improve our understanding of the molecular basis of various causes of graft dysfunction, and therefore suggest improved diagnosis, disease classification, and treatment.

Child↗
PubMed1998

The morphologic and molecular genetic categories of posttransplantation lymphoproliferative disorders are clinically relevant.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PT-LPDs) are a well-known complication of immunosuppression associated with solid organ transplantation. The clinical course of PT-LPDs is unpredictable; some patients experience regression of all lesions with a reduction in immunosuppression, whereas other patients, despite chemotherapy, radiation therapy, or surgery, rapidly die of their disease. In this study, the authors attempted to establish whether the previously described morphologic and molecular genetic categories of PT-LPD--plasmacytic hyperplasia (PH), polymorphic PT-LPD (polymorphic), and malignant lymphoma/multiple myeloma (ML/MM)--are clinically relevant and helpful in predicting the clinical outcome of patients who develop these lesions. METHODS: To determine the clinical significance of the morphologic and molecular genetic categories of PT-LPDs, the clinical characteristics of 32 solid organ transplant recipients (26 heart, 5 kidney, and 1 lung), including age, time from transplantation to development of PT-LPD, stage of disease, and clinical outcome, were compared with the morphologic and molecular genetic features of the 41 PT-LPDs that they developed (15 PH in 12 patients, 19 polymorphic in 16 patients, and 7 ML/MM in 6 patients). Clinical outcome was defined by the following categories: 1) regression (after a reduction in immunosuppression) and surgical resolution (by surgical excision, with or without a reduction in immunosuppression); 2) medical resolution (by chemotherapy and/or radiation therapy); and 3) no response. RESULTS: Although there was no difference in the time from transplantation to PT-LPD development among patients belonging to the three morphologic and molecular genetic categories, there was a significant difference in patient age at the time of PT-LPD development (P < 0.0098). Younger patients developed PH (mean age of 19 years), whereas older patients developed polymorphic PT-LPD (mean age of 35 years) and ML/MM (mean age of 56 years). Patients with PH presented with lower stages of disease (Stages I-II) than patients with ML/MM (P < 0.0004). Furthermore, there was a statistically significant trend between morphologic and molecular genetic category and clinical outcome, with decreased likelihood that lesions categorized as PH, polymorphic, or ML/MM would regress with a reduction in immunosuppression or be resolved by surgery, whereas those classified as ML/MM were more likely to exhibit no response to aggressive clinical intervention (P < 0.00006). Furthermore, no patients with PH died, whereas 20% with polymorphic PT-LPD and 67% with ML/MM died as a direct result of their PT-LPDs. CONCLUSIONS: This study strongly suggests that classification of PT-LPDs into the morphologic and molecular genetic categories PH, polymorphic, PT-LPD and ML/MM is clinically relevant.

Adult↗
PubMed1997

Molecular biology of acute lymphocytic leukemia.

Acute lymphoblastic leukemia (ALL) has been extensively studied and characterized at a molecular level. The identification and characterization of molecular lesions associated with ALL has led to advances in classification and prognosis of ALL, which in turn has been useful in stratifying ALL patients for treatment purposes. However, perhaps of greater long-term significance are insights into the mechanisms of leukemogenesis that have been provided by characterization of ALL at a molecular level. This review focuses on general themes and mechanisms of disease, concentrating on recent advances in the field, including the relationship of deregulated transcription factors to ALL, probable mechanisms of lymphoid translocations, and newly characterized genetic lesions, such as those involving tumor suppressor genes, 11q23 abnormalities, and 12p12 abnormalities.

Burkitt Lymphoma↗
PubMed1988

Molecular genetics and structure of the human immunodeficiency virus.

A novel human lymphotropic virus capable of crippling the immune system by infecting and destroying T4 antigen-positive cells is now known to be the etiologic agent of the acquired immune deficiency syndrome (AIDS). The AIDS or human immunodeficiency virus (HIV) belongs to a family of RNA viruses called retroviruses. Several strains of HIV have been molecularly cloned, and DNA sequence comparisons have established that the proviral DNA genome is 9.7 kilobase pairs. The genome possesses characteristic retrovirus features including structural genes, flanked by long terminal repeats, in the order gag, pol, and env and, in addition, four unique nonstructural genes, several of which appear to be essential in regulating virus replication. Electron microscopy has played an important role in elucidating structural, genetic, and molecular properties of HIV and has aided in its classification as a member of the Lentivirnae retrovirus subfamily. Heteroduplex mapping methodologies pertinent to these findings are described. Although the relationships show considerable divergence, the similarities between HIV and lentiviruses are profound and encompass an indistinguishable morphology, genome sequence homology and topography, genomic diversity, and overlapping biology, including a preference for infecting cells of the immune system, a cytopathic effect in vitro, and the ability to produce a persistent, slowly progressing, degenerative disease in vivo. The newest HIV class (HIV-2) has recently been molecularly characterized. HIV-2 also bears all the hallmarks of a lentivirus but is more closely related to simian immunodeficiency viruses than the previously described HIV-1, despite a similar biology. The HIV-lentivirus phylogenetic relationship has broad implications for the AIDS disease process and has given new importance to the study of the natural history and pathogenesis of animal lentiviruses in searching for clues to prevent the spread of AIDS.

Amino Acid Sequence↗
PubMedDate not supplied

Resolution of a taxonomic conundrum: an ultrastructural and molecular description of the life cycle of Pleistophora mulleri (Pfeiffer 1895; Georgevitch 1929).

The classification of a microsporidian parasite observed in the abdominal muscles of amphipod hosts has been repeatedly revised but still remains inconclusive. This parasite has variable spore numbers within a sporophorous vesicle and has been assigned to the genera Glugea, Pleistophora, Stempellia, and Thelohania. We used electron microscopy and molecular evidence to resolve the previous taxonomic confusion and confirm its identification as Pleistophora mulleri. The life cycle of P. mulleri is described from the freshwater amphipod host Gammarus duebeni celticus. Infection appeared as white tubular masses within the abdominal muscle of the host. Light and transmission electron microscope examination revealed the presence of an active microsporidian infection that was diffuse within the muscle block with no evidence of xenoma formation. Paucinucleate merogonial plasmodia were surrounded by an amorphous coat immediately external to the plasmalemma. The amorphous coat developed into a merontogenetic sporophorous vesicle that was present throughout sporulation. Sporogony was polysporous resulting in uninucleate spores, with a bipartite polaroplast, an anisofilar polar filament and a large posterior vacuole. SSU rDNA analysis supported the ultrastructural evidence clearly placing this parasite within the genus Pleistophora. This paper indicates that Pleistophora species are not restricted to vertebrate hosts.

Animals↗
PubMed2004

Primary immunodeficiency diseases: an update.

Although relatively rare, primary immune deficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into humoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known primary immunodeficiency diseases was created by a committee convened by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 100 PIDs has been elucidated. This update results from the latest meeting of this committee in Sintra, Portugal, June 2003, which followed 2(1/2) days of scientific discussions.

Animals↗
PubMed2004

Kohonen maps for prediction of binding to human cytochrome P450 3A4.

The drug development process utilizes the parallel assessment of activity at a therapeutic target as well as absorption, distribution, metabolism, excretion, and toxicity properties of molecules. The development of novel, reliable, and inexpensive computational methods for the early assessment of metabolism and toxicity is becoming increasingly an important part of this process. We have used a computational approach for the assessment of drugs and drug-like compounds which bind to the cytochromes P450 (P450s) with experimentally determined Km values. The physicochemical properties of these compounds were calculated using molecular descriptor software and then analyzed using Kohonen self-organizing maps. This approach was applied to generate a P450-specific classification of nearly 500 drug compounds. We observed statistically significant differences in the molecular properties of low Km molecules for various P450s and suggest a relationship between 33 of these compounds and their CYP3A4-inhibitory activity. A test set of additional CYP3A4 inhibitors was used, and 13 of 15 of these molecules were colocated in the regions of low Km values. This computational approach represents a novel method for use in the generation of metabolism models, enabling the scoring of libraries of compounds for their Km values to numerous P450s.

Cytochrome P-450 CYP3A↗
PubMed1984

Tabernaemontana L. (Apocynaceae): a review of its taxonomy, phytochemistry, ethnobotany and pharmacology.

The taxonomy, phytochemistry, ethnobotany, and pharmacology of the genus Tabernaemontana L. (Apocynaceae) is reviewed. The genus is currently being revised taxonomically; most of the segregate genera are being reunited with it and the number of species that will ultimately be recognized will probably be about 100. All the names encountered in the chemical and ethnobotanical literature have been evaluated as far as possible, and a list is presented of the recognized species and their synonyms. The biogenesis and classification of the indole alkaloids found in Tabernaemontana species is set out and some problems in the determination of their stereochemistry are discussed. To facilitate access to the information, three lists have been compiled: the alkaloids in alphabetical order; the alkaloids in order of increasing molecular weight; and the alkaloids grouped according to their biogenetic classification, together with the species and plant part(s) in which they are known to occur. Biogenetic and chemotaxonomic aspects are briefly considered. A table of the non-alkaloidal constituents is also included. The ethnobotany of individual Tabernaemontana species is outlined and an overall assessment made. Likewise, information on the pharmacology of crude extracts and individual alkaloids from Tabernaemontana species has been assembled and appraised.

Alkaloids↗
PubMed2002

A classification of covalent, ionic, and metallic solids based on the electron density.

The electron density of crystals contains all of the information required to complete a classification of their bonding types. We propose here a set of three different indexes, flatness, charge transfer, and molecularity, easily obtained from the experimental or theoretical electron density, which give rise to a classification in close resemblance to the classical van Arkel-Ketelaar diagrams.

Journal Article↗