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PubMed1991

Oncogene rearrangements in chronic B-cell leukemia.

Forty-four B-chronic lymphocytic leukemias (CLL) were studied by Southern blot analysis using probes for the Ig genes and bcl-1, bcl-2 (major, minor and 5' breakpoint region), bcl-3, c-myc, and retinoblastoma (Rb) loci. Eight cases had three or more rearranged JH bands, indicating oligoclonality, clonal evolution, or chromosomal translocation. One case had a rearrangement of the bcl-1 locus and three of the bcl-2 locus. In the first case, comigration of the rearranged bcl-1 and JH sequences indicated a t(11;14)(q13;q32) translocation, which, in contrast to previously described cases, seems to be completely reciprocal. One case with a bcl-2 rearrangement showed comigration of the bcl-2 major breakpoint region and a rearranged JH band. This indicates a t(14;18) (q32;q21). The two other cases showed rearrangements of the bcl-2 5' breakpoint region without apparent comigration. No rearrangements were detected of c-myc and bcl-3, located at chromosome 19, nor was a deletion of Rb found. All but three cases had CD5 expression. The exceptions included the t(11;14) and the t(14;18) cases. Our results confirm recent data on rearrangements at the 5' site of bcl-2 in CLL. Additionally, they corroborate the presumption that CD5-negative chronic B-cell leukemias should be considered apart from classical CLL.

Antigens, CD↗
PubMed1967

Ultrastructure of molar trophoblast. Observations on hydatidiform mole and chorioadenoma destruens.

The ultrastructure of molar trophoblast is described in hydatidiform mole and chorioadenoma destruens. Villous molar trophoblast exhibits only minor deviations from normal early villous trophoblast. Invasive trophoblast of chorioadenoma destruens shows features of more-active cell growth, multiplication, differentiation, and degradation. Evidence for evolution of highly differentiated syncytial trophoblast via intermediate stages from primitive undifferentiated cytotrophoblast is confirmed. Cytoplasmic inclusions resembling virus-like particles, observed in chorioadenoma destruens, have not been hitherto described in normal or pathologic trophoblast.

Chorionic Villi↗
PubMed2001

EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy.

BACKGROUND: Although so-called "benign" epilepsy with centrotemporal spikes (BECTS) always has an excellent prognosis with regard to seizure remission, behavioral problems and cognitive dysfunctions may sometimes develop in its course. To search for clinical or EEG markers allowing early detection of patients prone to such complications, the authors conducted a prospective study in a cohort of unselected patients with BECTS. METHODS: In 35 children with BECTS, academic, familial, neurologic, neuropsychological, and wake and sleep EEG evaluations were repeated every 6 to 12 months from the beginning of the seizure disorder up to complete recovery. RESULTS: In 25 of 35 patients (72%), behavioral and intellectual functioning remained unimpaired. In 10 of 35 patients (28%), educational performance and familial maladjustment occurred. These sociofamilial problems were correlated with impulsivity, learning difficulties, attention disorders, and minor (7/35 cases, 20%) or serious (3/35 cases, 8%) auditory-verbal or visual-spatial deficits. Worsening phases started 2 to 36 months after onset and persisted for 9 to 39 months. Occurrence of atypical evolutions was significantly correlated with five qualitative and one quantitative interictal EEG pattern: intermittent slow-wave focus, multiple asynchronous spike-wave foci, long spike-wave clusters, generalized 3-c/s "absence-like" spike-wave discharges, conjunction of interictal paroxysms with negative or positive myoclonia, and abundance of interictal abnormalities during wakefulness and sleep. Clinical deterioration was not linked with seizure characteristics or treatment. CONCLUSION: Different combinations of at least three of six distinctive interictal EEG patterns and their long-lasting (> or =6-month) persistence seem to be the hallmarks of patients with BECTS at risk for neuropsychological impairments.

Adolescent↗
PubMed1996

Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution.

Translation of aphthovirus RNA is initiated at an internal ribosome entry site (IRES) element, preceding the first functional AUG initiation codon. The effect of mutations at the base of domain 3 of the aphthovirus IRES on translation activity has been analyzed by site-directed mutagenesis and expression of bicistronic RNAs in transfected cells. The results have shown that the enhanced IRES activity associated with a single pyrimidine transition fixed in a persistent aphthovirus variant (E. Martínez-Salas, J. C. Sáiz, M. Dávila, G. J. Belsham, and E. Domingo, J. Virol. 67:3748-3755, 1993) is base specific. Mutations predicted to destabilize the base of domain 3 were detrimental to IRES function, but subsequent restoration of the RNA structure gave rise to fully competent IRES. In contrast, single or multiple mutations that did not affect predicted helical structures modified the relative efficiency of translation by at most 10-fold, suggesting that primary sequence also plays a role in IRES activity. A correlation between the energy of stabilization of the IRES structure and the efficiency of translation has been noted. None of the 15 mutations studied reached a level of initiation of translation comparable to that of the IRES from the persistent variant. The results indicate a critical participation of the base of domain 3 in the activity of the aphthovirus IRES, with a strong effect of secondary or higher-order structures and minor effects of primary structure.

Animals↗
PubMed2003

Evolution of cis-regulatory regions versus codifying regions.

Efforts to understand the genetic basis of evolutionary change have concentrated on proteins and their encoding DNA sequences. These studies have brought to light patterns and processes at the nucleotide level, yet the complex functional relationships between genetic variants and phenotypes remain poorly known. The realization that even a complete description of proteins and the effects of their activity will not suffice to understand the conditions under which they are time- and tissue-specifically expressed or repressed during development has refocused attention on cis-regulatory regions. In particular, promoter sequences are thought to hold the key for understanding the evolution of phenotypic differences between species. This is because of their complex organization into independent modules such that, unlike coding sequences in which mutations affect protein function every time the protein is expressed, mutations in cis-regulatory sequences may have minor or no pleiotropic effects. Complex information-encoding makes cis-regulatory regions poorly amenable to comparative methods designed for coding sequences. Some general conclusions are emerging as to how genetic variation is distributed across regulatory networks and the processes modulating the structure of this variation. We bring into this emerging scenario several recent findings pointing to different ways in which spliceosomal introns, pseudogenes and patterns of point mutation can be active players for the evolution of novel transcriptional profiles.

Animals↗
PubMed1999

A novel 8-bp insertion in codon 281 of p53 in a patient with acute lymphoblastic leukaemia and 2 separate leukaemic clones. Mutations in brief no. 219. Online.

We report a novel p53 insertion in a case of aggressive acute lymphoblastic leukaemia in a 16 year old male, in which 2 separate leukaemic clones were previously identified by T-cell receptor sigma and immunoglobulin heavy chain gene rearrangement studies. Initial p53 mutation screening of blast cells from 29 patients with acute leukaemia by PCR-denaturing gradient gel electrophoresis showed that 2 had a silent codon 213 polymorphism and only the index case had a somatic mutation identified to be an 8 bp insertion in codon 281 (5'CCGGGGGG-3'). This insertion was associated with the second, more aggressive clone which underwent clonal evolution and became resistant to cytotoxic chemotherapy. With an allele-specific primer in PCR, we were able to demonstrate the presence of this clone as a minority at disease presentation, and in 2 of 3 collections of peripheral blood progenitor cells.

Adolescent↗
PubMed2000

Recoupling of heteronuclear dipolar interactions with rotational-echo double-resonance at high magic-angle spinning frequencies.

Heteronuclear dipolar recoupling with rotational-echo double-resonance (REDOR) is investigated in the rapid magic-angle spinning regime, where radiofrequency irradiation occupies a significant fraction of the rotor period (10-60%). We demonstrate, in two model (13)C-(15)N spin systems, [1-(13)C, (15)N] and [2-(13)C, (15)N]glycine, that REDOR DeltaS/S(0) curves acquired at high MAS rates and relatively low recoupling fields are nearly identical to the DeltaS/S(0) curve expected for REDOR with ideal delta-function pulses. The only noticeable effect of the finite pi pulse length on the recoupling is a minor scaling of the dipolar oscillation frequency. Experimental results are explained using both numerical calculations and average Hamiltonian theory, which is used to derive analytical expressions for evolution under REDOR recoupling sequences with different pi pulse phasing schemes. For xy-4 and extensions thereof, finite pulses scale only the dipolar oscillation frequency by a well-defined factor. For other phasing schemes (e.g., xx-4 and xx-4) both the frequency and amplitude of the oscillation are expected to change.

Algorithms↗
PubMed1997

Two divergent intragenomic rDNA ITS2 types within a monophyletic lineage of the fungus Fusarium are nonorthologous.

The evolutionary history of the phytopathogenic Gibberella fujikuroi complex of Fusarium and related species was investigated by cladistic analysis of DNA sequences obtained from multiple unlinked loci. Gene phylogenies inferred from the mitochondrial small subunit (mtSSU) rDNA, nuclear 28S rDNA, and beta-tubulin gene were generally concordant, providing strong support for a fully resolved phylogeny of all biological and most morphological species. Discordance of the nuclear rDNA internal transcribed spacer 2 (ITS2) gene tree is due to paralogous or xenologous ITS2 sequences. PCR and sequence analysis demonstrated that every strain of the ingroup species tested possesses two highly divergent nonorthologous ITS2 types designated type I and type II. Only the major ITS2 type, however, is discernable when PCR products are amplified and sequenced directly with conserved primers. The minor ITS2 type was recovered using ITS2 type-specific PCR primers. Distribution of the major ITS2 type within the species lineages exhibits a homoplastic pattern of evolution, thus obscuring true phylogenetic relationships. The results suggest that the ancestral ITS2 types may have arisen following an ancient interspecific hybridization or gene duplication which occurred prior to the evolutionary radiation of the Gibberella fujikuroi complex and related species of Fusarium. The results also indicate that current morphological-based taxonomic schemes for these fungi are unnatural and a new classification is required.

Base Sequence↗
PubMed1978

Kinetic factors and form determination of the head of bacteriophage T4.

The form of the bacteriophage T4 prehead is described by its icosahedral symmetry, its diameter, and its length. We show how each of these parameters is regulated during prehead formation and ascribe specific form-determining functions to the prehead proteins. The major protein of the head shell can assemble in several different forms. The structure produced in vivo depends on the rate of synthesis of the major protein relative to the rates of synthesis of minor shell proteins and the major core protein. From our observations, we propose a model for form determination of the prehead and suggest a pathway for the evolution of its prolate shape.

Biological Evolution↗
PubMed1996

A simplified T2-T3 thoracoscopic sympathicolysis technique for the treatment of essential hyperhidrosis: short-term results in 100 patients.

A simplified one-time bilateral thoracoscopic T2-T3 sympathicolysis technique using single-lumen endotracheal intubation with high frequency jet ventilation and electrocautery destruction ("sympathicolysis") of the sympathetic ganglia was applied in 100 consecutive patients with severe essential hyperhidrosis (EH). Providing a pleural space can be created, this technique was proven simple and safe, and short-term clinical results were excellent: palmar hyperhidrosis was cured in 98% of patients, and axillar and plantar improvement was achieved in 62 and 65% of patients, respectively. Side-effects and complications were minor (compensatory hyperhidrosis) or self-limiting (pain). These data confirm the safety and efficacy of thoracoscopic sympathetic interventions for the treatment of EH, and support the evolution toward simplified methodologies.

Adolescent↗
PubMed1988

Do woody plants operate near the point of catastrophic xylem dysfunction caused by dynamic water stress? : answers from a model.

We discuss the relationship between the dynamically changing tension gradients required to move water rapidly through the xylem conduits of plants and the proportion of conduits lost through embolism as a result of water tension. We consider the implications of this relationship to the water relations of trees. We have compiled quantitative data on the water relations, hydraulic architecture and vulnerability of embolism of four widely different species: Rhizophora mangle, Cassipourea elliptica, Acer saccharum, and Thuja occidentalis. Using these data, we modeled the dynamics of water flow and xylem blockage for these species. The model is specifically focused on the conditions required to generate ;runaway embolism,' whereby the blockage of xylem conduits through embolism leads to reduced hydraulic conductance causing increased tension in the remaining vessels and generating more tension in a vicious circle. The model predicted that all species operate near the point of catastrophic xylem failure due to dynamic water stress. The model supports Zimmermann's plant segmentation hypothesis. Zimmermann suggested that plants are designed hydraulically to sacrifice highly vulnerable minor branches and thus improve the water balance of remaining parts. The model results are discussed in terms of the morphology, hydraulic architecture, eco-physiology, and evolution of woody plants.

Journal Article↗
PubMedDate not supplied

Evolution of migraine after a 10-year follow-up.

OBJECTIVE: To assess the evolution of headaches in a workplace cohort over a 10-year period. BACKGROUND: Migraine headaches are associated with significant handicap in everyday activities and poor quality of life. The prevalence of migraine shows a bell-shaped age distribution with a peak during the third and fourth decades. However, there is little longitudinal data available on the natural history of this condition. A prospective health survey undertaken in a large workplace cohort since 1989 provides an opportunity to assess the evolution of migraine and other headache syndromes over a 10-year period. METHODS: A sample of 2500 subjects who reported regular headaches was chosen at random from those with headache identified in a cohort of 46,244 employees of the French national power company aged between 35 and 50 years in 1989 participating in a yearly health survey. In 1993, all subjects were sent a headache questionnaire to complete and return. In 2003, an identical questionnaire was sent to all subjects who had returned exploitable data in 1993. Headache diagnosis was assigned retrospectively using the International Headache Society (IHS) criteria to migraine (IHS categories 1.1 and 1.2), migrainous disorder (IHS category 1.7), or other episodic headaches. RESULTS: Of 2500 subjects sampled, 2051 (82%) returned exploitable data for the first questionnaire in 1993. In 2003, 1250 (61%) of these provided a second data set. In 1993, 623 (30.4%) of subjects fulfilled diagnostic criteria for migraine. However, only 37% of these retained the diagnosis 10 years later. In contrast, the proportion of subjects with other forms of episodic headache rose from 23.7% to 31.6%. In 2003, 9.5% of the sample were headache-free. Retention or acquisition of a diagnosis of migraine was more common in women than in men, and age was associated with evolution to a less severe headache syndrome. In those subjects who continued to have headaches, frequency and severity were lower at the second assessment. CONCLUSIONS: Only a minority of subjects diagnosed with migraine or migrainous disorder retain the diagnosis 10 years later, with most subjects evolving to a less disabling headache type.

Adult↗
PubMed2002

Investigating evolutionary lines of least resistance using the inverse protein-folding problem.

We present a polynomial time algorithm for estimating optimal HP sequences that fold to a specified target protein conformation based on Sun et al's Grand Canonical (GC) model. Application of the algorithm to related proteins taken from the PDB allows us to explore the nature of the protein genotype:phenotype map. Results suggest: (1) that the GC model captures important biological aspects of the mapping between protein sequences and their corresponding structures, and (2) the set of sequences that map to a target structure with optimal energy is affected by minor differences in structure.

Algorithms↗
PubMed2005

Allergy to mammal's meat in adult life: immunologic and follow-up study.

UNLABELLED: Allergy to bovine meat and Bovine serum albumin (BSA) is exceptional, especially in the adult life. BSA is considered a minor allergen in cow's milk allergy, but there is little information about this antigen in reactions produced by other beef products as meat. To our knowledge, evolutive studies of beef's allergic patients have not been reported. OBJECTIVE: To present one patient with several allergic reactions (urticaria-angioedema) after eating different mammals' meat. METHODS: The patient underwent allergy testing through skin prick test (SPT), specific IgE detection and SDS-PAGE Immunoblotting and Immunodot inhibition studies. Periodic determinations of specific IgE to meats and epithelia were performed. RESULTS: Routine studies for chronic urticaria were normal or negative. SPT showed positive responses to pork, cow, rabbit and lamb meat, and dog, pork, sheep and cow epithelia. It was negative to cat, horse, guinea pig, rabbit, lamb, mouse epithelia, mixture of feathers, cow milk, soybean, mustard, mites and chicken meat and Anisakis simplex. Intradermal testing to BSA was positive. Determinations of specific IgE were positive to beef meat, lamb meat, pork meat and rabbit meat, dog, cat, cow, sheep and pork dander, cow's milk, and negative to chicken meat. Immunoblot and immunodot studies showed IgE recognition bands to bovine and lamb meat which were totally inhibited by BSA. A progressive reduction of the total and specific IgE, the latter until its total negativization, has been observed in the following three-year period. CONCLUSION: We report a case of IgE-mediated urticaria-angioedema due to BSA hypersensitivity, possibly induced by a subclinical sensitivity to dog and cat epithelium. The exclusion diet in patients allergic to these foods may be a progressive loss of clinical allergy.

Angioedema↗
PubMed1987

Thymopentin (TP-5) therapy during lymphadenopathy syndrome (LAS/ARC): preliminary report.

Persistent generalized lymphadenopathy during HIV infection is now a well classified syndrome featuring multiple chronic lymph node enlargement frequently associated with further symptoms (diarrhea, nocturnal sweating, loss of weight, fever): it is invariably accompanied by serious alterations of the cell-mediated immunity including lymphopenia, reduced number of helper lymphocytes in circulation, inversion of the helper/suppressor ratio, lower proliferative response in vitro and deficient delayed skin sensitivity tests. Minor opportunistic infections are also more frequent, the most widespread being chronic oral candidiasis. Whenever several of these signs are associated in a single patient, especially if the immunitary deficit is severe, an immunomodulating treatment is indicated to improve the lymphocyte functionality and finally to modify any evolutive tendency. The Authors give the preliminary results of a pilot study carried out on 12 patients with LAS/ARC treated with Thymopentin at a dosage of 50 mg by intra muscular injection on alternate days for cycles of 30 days. Compared with 14 untreated patients, the subjects receiving therapy showed a more stable immunological picture, and improvement in subjective symptoms and a better therapeutic response to minor opportunistic infections.

AIDS-Related Complex↗
PubMed1993

[Phylogenesis of the extracellular matrix].

The extracellular matrix constitutes a highly organized intercellular medium. In multicellular animals, it plays important functions for cell cohesion and for the modulation of cell differentiation and behaviour as well. All the investigations conducted in non-vertebrate species have shown that the extracellular matrix is present at the onset of the multicellular life and throughout the animal kingdom. The collagen fibrils are the most constant element. Recent data on the structure of fibrillar collagen molecules and on the organization of the corresponding genes, obtained in sponges and sea-urchins have shown the remarkable conservation of these fibrillar collagens during evolution. This even emphasize their very likely fundamental function. These results, associated with data provided by morphological and biochemical informations obtained in cnidarians suggest that these primitive fibrillar collagens are the direct precursors of some vertebrate minor fibrillar collagens such as type V. Other collagens, with interrupted triple helix, are more variable and their characterization in sponges leads to consider these non-fibrillar collagens as precursors of basement membrane collagens, of fibril-associated collagens (the FACITs collagens), of the so-called "epithelial" collagens. They were probably used as sticking devices, anchoring the animal to its substratum, or as covering layers (cuticles, sheaths), and even as skeletons (i.e. the bath sponge). Adhesive molecules of higher animals ensure the mediation of the interactions between cells (via their membrane receptors of the integrin type) and the fibrous network of the extracellular matrix. It is the same situation at the beginning of the evolution of the multicellular animals where fibronectin, tenascin and then laminin are present. Proteoglycans too are components of primitive extracellular matrices. At last, only collagen mineralized by calcium phosphate (in bone) and elastin (in elastic fibers and laminae) seem to be restricted to vertebrates.

Animals↗
PubMed1994

Evolution and selection of hepatitis C virus variants in patients with chronic hepatitis C.

It has been shown that hepatitis C virus (HCV) populations in vivo are composed of different but highly homologous HCV genomes (quasispecies) as shown in the hypervariable region (HVR) that exists in the N-terminal of the envelope 2 gene of HCV, and that the predominant sequence of the HVR of HCV genomes changes rapidly over time. To further investigate genetic backgrounds of the change in the HVR of HCV genomes, 45 plasma samples serially obtained from nine patients with chronic hepatitis C were studied using population-based analyses. Total RNA was recovered and the envelope gene containing the HVR was amplified by the reverse transcription and nested polymerase chain reaction. The amplified cDNA was examined by the single strand conformation polymorphism (SSCP) analysis. Furthermore, 43 HCV sequences, separated by the SSCP analysis from three patients were determined by the dideoxy chain termination method, and the phylogenetic analysis was performed using the neighbor joining method. The SSCP analysis demonstrated that HCV population within each individual were composed of 1 to 6 quasispecies. These quasispecies populations in vivo changed sequentially in eight of nine patients. Gradual selections of coexisting quasispecies were observed over 6- to 18-month periods in three patients, whereas complete replacements of previous quasispecies by new quasispecies were repeatedly observed over few-month intervals in five patients. The phylogenetic analysis on these quasispecies revealed the continuous accumulation of mutations in two patients and discontinuous appearance of evolutionarily distant quasispecies in one patient. These results indicate that HCV genomes in vivo form quasispecies populations, and that these quasispecies populations change during the natural course of chronic infection. Genetic mechanisms underlining the change of the HVR of HCV genome appear to be either continuous accumulation of mutations or selective overgrowth of preexisting minor variants from the large spectrum of quasispecies populations.

Aged↗
PubMed2006

Sudden origins: a general mechanism of evolution based on stress protein concentration and rapid environmental change.

A major theme in Darwinian evolutionary theory is that novelty arises through a process in which organisms and their features are gradually transformed. Morgan provided Darwinism and the evolutionary synthesis with the idea that minor mutations produce the minuscule morphological variations on which natural selection then acts, and that, although mutation is random, once a process of gradual genetic modification begins, it becomes directional and leads to morphological, and consequently organismal, transformation. In contrast, studies on the role of cell membrane physical states in regulating the expression of stress proteins in response to environmental shifts indicate the existence of a downstream mechanism that prevents or corrects genetic change (i.e., maintains "DNA homeostasis"). However, episodic spikes in various kinds of environmental stress that exceed an organism's cells' thresholds for expression of proper amounts of stress proteins responsible for protein folding (including stochastically occurring DNA repair) may increase mutation rate and genetic change, which in turn will alter the pattern of gene expression during development. If severe stress disrupts DNA homeostasis during meiosis (gametogenesis), this could allow for the appearance of significant mutational events that would otherwise be corrected or suppressed. In evolutionary terms, extreme spikes in environmental stress make possible the emergence of new genetic and consequent developmental and epigenetic networks, and thus also the emergence of potentially new morphological traits, without invoking geographic or other isolating mechanisms.

Animals↗