Biological Features (biological + feature)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Role of ancillary techniques in diagnosing and subclassifying non-Hodgkin's lymphomas on fine needle aspiration cytology

P. DeyArticle first published online: 8 SEP 200
Non-Hodgkin's lymphomas (NHL) are tumours of the lymphoid cells. During the process of development of lymphoid cells, neoplasia may evolve at any point. Neoplastic cells usually carry the imprint of cell of origin at the stage of origin. Various types of NHL may have similar morphology with wide variation in origin, immunophenotype and other biological features. Different ancillary laboratory techniques may help to overcome the limitations of morphology in this aspect. The commonly used ancillary techniques in lymphomas are immunocytochemistry (IC), flow cytometry, Southern blot (SB) technique, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In addition, laser scanning cytometry (LSC) and DNA microarray technologies are in the research phase. Various laboratory techniques are used for immunophenotyping, demonstration of monoclonality, identification of chromosomal translocation, assessment of cell kinetics and expression of mRNA in the tumour cells. Flow cytometry helps in rapid immunophenotying of NHL and it has an added advantage over IC in recognizing the co-expression of CD markers. Fine needle aspiration cytology (FNAC) combined with flow immunophenotyping may help us to diagnose and subclassify certain NHLs, such as follicular lymphoma and mantle cell lymphoma, which were previously recognized as pure morphological entities. Loss of morphology is one of the important limitations of flow cytometry. LSC can overcome this limitation by studying morphology along with the immunophenotyping pattern of individual cells. Chromosomal changes in NHL can be identified by SB, PCR and FISH. Molecular diagnosis of NHL helps in diagnosis, subclassification, prognostic assessment and even in planning of therapy. DNA microarray is a relatively newer and promising technology. It gives information about the expression of several thousands of genes in a tumour in a single experiment. In the near future, FNAC combined with ancillary techniques may play a major role in diagnosis, subclassification and management of lymphomas. [source]

Validity of ,post-traumatic stress disorder with secondary psychotic features': a review of the evidence

M. H. Braakman
Objective:, To review the evidence from empirical studies regarding the validity of ,post-traumatic stress disorder with secondary psychotic features' (PTSD-SP) as a separate diagnostic entity. Method:, The authors performed a review tracing publications between 1980 and January 2008. Results:, Twenty-four comparative studies were included. These studies indicate that PTSD-SP is a syndrome that comprises PTSD-symptoms followed in time by the additional appearance of psychotic features. The psychotic features are not confined to episodes of re-experiencing, but remain present continuously. PTSD-SP seems to have some biological features differentiating it from schizophrenia and PTSD, e.g. there are differences in smooth pursuit eye movement patterns, concentrations of corticotropin-releasing factor and dopamine ,-hydroxylase activity. Conclusion:, There is currently not yet full support for PTSD-SP as a nosological entity. However, the delineation of PTSD-SP from other psychiatric syndromes is notable and biological studies seem to support the validity as a separate diagnostic entity. [source]

Nucleotide-binding domain 1 of cystic fibrosis transmembrane conductance regulator

FEBS JOURNAL, Issue 17 2000
Production of a suitable protein for structural studies
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This protein belongs to the large ATP-binding cassette (ABC) family of transporters. Most patients with cystic fibrosis bear a mutation in the nucleotide-binding domain 1 (NBD1) of CFTR, which plays a key role in the activation of the channel function of CFTR. Determination of the three dimensional structure of NBD1 is essential to better understand its structure,function relationship, and relate it to the biological features of CFTR. In this paper, we report the first preparation of recombinant His-tagged NBD1, as a soluble, stable and isolated domain. The method avoids the use of renaturing processes or fusion constructs. ATPase activity assays show that the recombinant domain is functional. Using tryptophan intrinsic fluorescence, we point out that the local conformation, in the region of the most frequent mutation ,F508, could differ from that of the nucleotide-binding subunit of histidine permease, the only available ABC structure. We have undertaken three dimensional structure determination of NBD1, and the first two dimensional 15N- 1H NMR spectra demonstrate that the domain is folded. The method should be applicable to the structural studies of NBD2 or of other NBDs from different ABC proteins of major biological interest, such as multidrug resistance protein 1 or multidrug resistance associated protein 1. [source]

Penicillin Binding Proteins: key players in bacterial cell cycle and drug resistance processes

Pauline Macheboeuf
Abstract Bacterial cell division and daughter cell formation are complex mechanisms whose details are orchestrated by at least a dozen different proteins. Penicillin-binding proteins (PBPs), membrane-associated macromolecules which play key roles in the cell wall synthesis process, have been exploited for over 70 years as the targets of the highly successful ,-lactam antibiotics. The increasing incidence of ,-lactam resistant microorganisms, coupled to progress made in genomics, genetics and immunofluorescence microscopy techniques, have encouraged the intensive study of PBPs from a variety of bacterial species. In addition, the recent publication of high-resolution structures of PBPs from pathogenic organisms have shed light on the complex intertwining of drug resistance and cell division processes. In this review, we discuss structural, functional and biological features of such enzymes which, albeit having initially been identified several decades ago, are now being aggressively pursued as highly attractive targets for the development of novel antibiotherapies. [source]

Interaction between wind-induced seiches and convective cooling governs algal distribution in a canyon-shaped reservoir

Summary 1. Wind is considered the dominant factor controlling phytoplankton distribution in lentic environments. In canyon-shaped reservoirs, wind tends to blow along the main axis generating internal seiches and advective water movements that jointly with biological features of algae can produce a heterogeneous phytoplankton distribution. Turbulence generated by wind stress and convection will also affect the vertical distribution of algae, depending on their sinking properties. 2. We investigated the vertical and horizontal distribution of phytoplankton during the stratification period in Sau Reservoir (NE Spain). Sites along the main reservoir axis were sampled every 4 h for 3 days, and profiles of chlorophyll- a and temperature were made using a fluorescent FluoroProbe, which can discriminate among the main algal groups. Convective and wind shear velocity scales, and energy dissipation were calculated from meteorological data, and simulation experiments were performed to describe non-measured processes, like vertical advection and sinking velocity of phytoplankton. 3. Wind direction changed from day to night, producing a diel thermocline oscillation and an internal seiche. Energy dissipation was moderate during the night, and mainly attributed to convective cooling. During the day the energy dissipation was entirely attributed to wind shear, but values indicated low turbulence intensity. 4. The epilimnetic algal community was mainly composed of diatoms and chlorophytes. Chlorophytes showed a homogeneous distribution on the horizontal and vertical planes. Diatom horizontal pattern was also homogeneous, because the horizontal advective velocities generated by wind forcing were not high enough to develop phytoplankton gradients along the reservoir. 5. Diatom vertical distribution was heterogeneous in space and time. Different processes dominated in different regions of the reservoir, due to the interaction between seiching and the daily cycle of convective-mediated turbulence. As the meteorological forcing followed a clear daily pattern, we found very different diatom sedimentation dynamics between day and night. Remarkably, these dynamics were asynchronous in the extremes of the seiche, implying that under the same meteorological forcing a diatom population can show contrasting sedimentation dynamics at small spatial scales (approximately 103 m). This finding should be taken into account when interpreting paleolimnological records from different locations in a lake. 6. Vertical distribution of non-motile algae is a complex process including turbulence, vertical and horizontal advection, variations in the depth of the mixing layer and the intrinsic sinking properties of the organisms. Thus, simplistic interpretations considering only one of these factors should be regarded with caution. The results of this work also suggest that diatoms can persist in stratified water because of a synergistic effect between seiching and convective turbulence. [source]

The biology and ecology of lotic rotifers and gastrotrichs

Claudia Ricci
Summary 1The occurrence of Rotifera and Gastrotricha in the meiobenthos of lotic habitats is reviewed. About 150 rotifer and 30 gastrotrich species are reported in such habitats worldwide. 2The two phyla share some morphological and biological features that might account for their presence in the meiofauna. Small-size, a soft and elongate body, adhesive glands on the posterior body end, movement through cilia, relatively short life cycles, parthenogenesis and dormant stages are common characteristics. 3Most species of both taxa inhabiting the superficial sediments in streams and rivers may move downward into the hyporheos in response to both biotic (predation) and abiotic (spates, erosion, desiccation) disturbances. [source]

Pyothorax-associated lymphoma (PAL): a western case with marked angiocentricity and review of the literature

A Androulaki
Aims :,To report a case of pyothorax-associated lymphoma in a non-immunocompromised 78-year-old man with a 45-year history of tuberculous pleuritis and left pleural effusion. Pyothorax-associated lymphoma is a high-grade non-Hodgkin's lymphoma occurring in 2% of patients with long-standing tuberculous pleuritis and pyothorax. Pyothorax-associated lymphoma is frequently Epstein,Barr virus (EBV)-associated, mainly reported in Japan but exceedingly rare in western countries. Methods and results :,Histology revealed a high-grade, diffuse large B-cell lymphoma with immunoblastic and plasmacytoid features and marked angiocentricity with focal destruction of the vessel walls. Immunohistochemistry revealed a post germinal B-cell phenotype. RNA in-situ hybridization and molecular analysis showed a latent EBV infection and absence of human herpes virus-8 (HHV-8). Conclusions :,Pyothorax-associated lymphoma represents a rare but distinctive type of diffuse large B-cell lymphoma, with characteristic clinico-epidemiological, immunohistological, and biological features. [source]

Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry

Abstract Background: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms. Methods: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non-functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin-embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used an ,-centromeric enumeration probe for chromosome 17. Results: The mean Ki-67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein. Conclusions: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor. [source]

How important is climate?

Effects of warming, fish on phytoplankton in shallow lake microcosms, nutrient addition
Summary 1Climate is changing. Predictions are for at least a 3 °C rise in mean temperature in northern Europe over the next century. Existing severe impacts of nutrients and inappropriate fish stocking in freshwater systems remain. 2Effects of warming by 3 °C above ambient, nutrient addition and the presence or absence of sticklebacks Gasterosteus aculeatus were studied in experimental microcosms dominated by submerged plants, mimicking shallow lake ecosystems. 3Warming had considerably smaller effects on the phytoplankton community than did fish and nutrients. It had very minor effects on chlorophyll a and total phytoplankton biovolume. However, it significantly decreased the biovolumes of Cryptophyceae (a major component in the controls) and Dinophyceae. Contrary to expectation, warming did not increase the abundance of blue-green algae (cyanophytes). Warming decreased the abundances of Cryptomonas erosa (Cryptophyceae) and Oocystis pusilla (Chlorophycota) and increased those of two other green algae, Tetraedron minimum and Micractinium pusillum. It had no effect on a further 17 species that were predominant in a community of about 90 species. 4Fish and nutrients, either together or separately, generally increased the crops of most of the 21 abundant species and of the algal groups. Exceptions were for diatoms and chrysophytes, which were very minor components of the communities. Fish, but neither nutrients nor warming, increased the number of species of phytoplankton detected. This was probably through removal of zooplankton grazers, and parallels terrestrial studies where the presence of top predators, by controlling herbivores, leads to increased plant diversity. 5There was no particular pattern in the taxonomy or biological characteristics of those species affected by the treatments. In particular, there was no link between organism size (a surrogate for many important biological features of phytoplankton species) and the effects of warming, nutrient addition or presence or absence of fish. However, all species were relatively small and potentially vulnerable to grazing. 6Synthesis and applications. The results suggest that fears of an increasing abundance of cyanophytes with current projections of global warming may be unrealized, at least in shallow unstratified lakes still dominated by macrophytes. However, they emphasize that eutrophication and fish manipulations remain very important impact factors that determine the abundance of phytoplankton and subsequent problems caused by large growths. [source]

Large-scale geographical trends in fruit traits of vertebrate-dispersed temperate plants

Arndt Hampe
Abstract Aim, To assess large-scale geographical trends in the character of fleshy, vertebrate-dispersed fruits. Location, Europe between central Sweden and southern Spain. Methods, Analyses of fruit of sixty-three plant species from twenty-nine families were compiled from four regional data sets. Four structural and five chemical fruit traits were analysed intraspecifically to control rigorously for phylogenetic lineage effects. Trends were examined in relation to various biological features of the considered species. Results, Contents of soluble carbohydrate and lipids decreased markedly northwards. Fruit diameter and fresh mass peaked at the wettest site, while the pulp water content remained more constant throughout the gradient than any other fruit trait. Ash content, seed number and seed mass did not change, while the nitrogen content showed conflicting trends. No relation was detected between observed variation in fruit traits and fruit type, fruit colour, ripening season, plant growth form, leaf longevity, or geographical distribution of the considered plant species. Main conclusions, Considerable intraspecific variability exists in vertebrate-dispersed fruits on large geographical scales. Climate presumably affects particularly those traits related to carbon and water gain and storage. Most research on fruit,frugivore interactions has been carried out on small spatial scales and failed to find matchings between frugivore communities and the character of fleshy fruits. I suggest that explicitly addressed large-scale surveys on the geographical variability of fruits and their disperser assemblages are needed to elucidate their spatial patterns and to determine the extent to which fleshy fruit traits are shaped by animals and/or abiotic factors. [source]

Gorham-Stout Syndrome: A Monocyte-Mediated Cytokine Propelled Disease,

Silvia Colucci
Abstract We studied the biological features and the immunophenotype of a cell culture established from the lesion of soft tissues of a woman affected by Gorham-Stout syndrome. We found that these cells belonged to a monocytic lineage with some characteristics of immature osteoclasts and were able to release large amounts of osteoclastogenic and angiogenic molecules that may contribute to disease progression. Introduction: Gorham-Stout syndrome is a rare disease characterized by osteolysis and proliferation of vascular or lymphatic vessels, with a severe outcome. Its etiology and the identification of the cell types involved are completely unknown. Materials and Methods: A cell culture from a lesion of soft tissues was established, and its behavior in vitro and in immunodeficient mice was studied. We analyzed (1) the cell phenotype by flow cytometry; (2) the adhesive and migratory properties on different substrates; (3) the ability to differentiate into mature osteoclasts; (4) the production of osteclastogenic and angiogenic molecules; (5) the in vivo angiogenic activity of the cells subcutaneously implanted in mouse in a Matrigel plug; and (6) the ability to recapitulate the disease when transplanted in nude mice. Results and Conclusions: The established culture consisted of a morphologically homogeneous cell population belonging to a monocytic lineage having some features of an osteoclast-like cell type. Cells had an invasive phenotype, were angiogenic, and produced osteoclastogenic (IL-6, TGF-,1, IL-1,) and angiogenic (vascular endothelial growth factor-A {VEGF-A}, CXCL-8) molecules when challenged with inflammatory cytokines. Immunodeficient mice injected with these cells did not show any bone lesions or vascular alteration, but had high amounts of circulating human IL-6 and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of these findings. These data suggest that cells of monocyte-macrophage lineage play an essential role in the pathogenesis of Gorham-Stout disease, whose progression is propelled by cytokine circuits that accelerate angiogenesis and osteoclastogenesis. [source]

Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model

Isao Okayasu
Abstract Background: As an important mechanism underlying the increased risk of colorectal carcinoma development in patients with long-standing ulcerative colitis, promotion as a result of the regenerative process has been proposed. In the present study, a dysplasia-carcinoma sequence in a novel repeated colitis model in mice is documented. Methods: Repeated colitis was induced by nine administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54 000): each administration cycle comprised 3% DSS for 7 days followed by distilled water for the subsequent 14 days, to give conditions similar to the clinically observed active and remission phases in humans. Results: Multiple colorectal tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in 25 mice. These neoplastic lesions consisted of tubular structures, presenting as various types of elevated, flat and depressed tumor, similar to those in ulcerative colitis patients. A time-course study with assessment of the severity of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS administration cycle revealed a high level of regenerative activity in the colitis-affected mucosal epithelia. Conclusion: Thus, with the present repeated colitis model, regeneration and neoplastic lesions were apparent, the biological features of which provide evidence of a colorectal dysplasia,invasive carcinoma sequence in ulcerative colitis. [source]


Corinne R. Lehr
The unicellular eukaryotic algae Cyanidium, Galdieria, and Cyanidioschyzon (herein referred to as "cyanidia") are the only photoautotrophs occurring in acidic (pH<4.0) geothermal environments at temperatures above 40°C. In Yellowstone National Park (YNP), we examined an annual event we refer to as "mat decline," where cyanidial mats undergo a seasonably defined color fading. Monthly sampling of chemical, physical, and biological features revealed that spring aqueous chemistry was essentially invariant over the 1-year sampling period. However, multiple regression analysis suggested that a significant proportion of algal most probable number (MPN) count variation could be explained by water temperature and UV,visible (VIS) light exposure. Irradiance manipulations (filtering) were then coupled with 14CO2 incorporation experiments to directly demonstrate UV inhibition of photosynthesis. Population dynamics were also evident in 18S rDNA PCR clone libraries, which were different in composition at MPN maxima and minima, and again evident in PCR-amplified chloroplast genomic short sequence repeat (SSR) analysis. PCR-cloned SSRs of the YNP isolates and mats were very similar to Cyanidioschyzon merolae Luca, Taddei et Varano, although distance analysis could distinguish the YNP cyanidia from the genome sequenced C. merolae that was isolated in Italy. Unexpectedly, while phylogenetic analysis of 18S rDNA sequences and SSR sequences derived from YNP cyanidial mats and pure cultures suggested these algae are most closely related to C. merolae (99.7% identity), cell morphology was consistent with the genera Galdieria and Cyanidium. [source]

Individualized and time-variant model for the functional link between thermoregulation and sleep onset

Summary This study makes use of control system model identification techniques to examine the relationship between thermoregulation and sleep regulation. Specifically, data-based mechanistic (DBM) modelling is used to formulate and experimentally test the hypothesis, put forth by Gilbert et al. [Sleep Med. Rev.8 (2004) 81], that there exists a connection between distal heat loss and sleepiness. Six healthy sleepers each spent three nights and the following day in the sleep laboratory: an adaptation, a cognitive arousal and a neutral testing day. In the cognitive arousal condition, a visit of a television camera crew took place and subjects were asked to be interviewed. During each of the three 25-min driving simulator tasks per day, the distal-to-proximal gradient and the electroencephalogram are recorded. It is observed from these experimental data that there exists a feedback connection between thermoregulation and sleep. In addition to providing experimental evidence in support of the Gilbert et al. (2004) hypothesis, the authors propose that the nature of the feedback connection is determined by the nature of sleep/wake state (i.e. NREM sleep versus unwanted sleepiness in active subjects). Besides this, an individualized and time-variant model for the linkage between thermoregulation and sleep onset is presented. This compact model feeds on real-time data regarding distal heat loss and sleepiness and contains a physically meaningful parameter that delivers an individual- and time-depending quantification of a well known biological features in the field of thermoregulation: the thermoregulatory error signal Thypo(t),Tset(t). A validation of these physical/biological features emphasizes the reliability and power of DBM in describing individual differences related to the sleep process. [source]

Restoration of Lake Geneva: Expected versus observed responses of phytoplankton to decreases in phosphorus

Orlane Anneville
Abstract Long-term phytoplankton responses in Lake Geneva to a decline in phosphorus (P) loading are examined in terms of summer (July,September) biomass and community structure. With the rapid development of human activity on its banks and within its catchment area in the 1960s, this large subalpine hydrosystem shifted from oligotrophy to eutrophy within approximately one decade. Measures to reduce P loading were initiated successfully in the mid-1970s, when total P concentrations in the winter overturn altered from 90 ,g/L in 1980 to 40 ,g/L in 1998. Until the 1990s, algal descriptors improved as expected (biomass decline, reappearance of diatom species, increased contribution of nanoplankton). Then, paradoxically, and in contrast to the reappearance of oligotrophic species, summer algal biomass began to increase. Pre-summer (period prior to the beginning of the clear water phase) dissolved inorganic phosphorus concentrations and summer phytoplankton composition presented similar interannual trends. However, the succession of phytoplankton structure during the reoligotrophication phase differed greatly from that during the eutrophication period, and a recent abnormal upward trend in algal densities is mainly the result of the development of large species that formerly were only common from late September until November. This community change, mainly triggered by filamentous (Mougeotia gracillima, Tribonema) or motile forms (Dinobryon sociale, Cryptophycea), seems to have been induced by the earlier and greater deepening of the P-depleted layer. In addition to milder summers, this massive development of larger forms seems to be favoured by four of their biological features: tolerance to warm temperatures, tolerance to low-light intensity (might exploit deeper layers where P is not yet limiting), shapes not only providing a large surface to volume ratio or motility (adaptation to low-nutrient concentrations), but increasing resistance to zooplankton grazing. This paradoxical trend, perhaps reinforced by the decline on roach Rutilus rutilus abundance (an opportunistic planktivore), is likely to remain until the P-depleted zone is extended below the layers that can be frequently resupplied in nutrients by hydrodynamic processes. [source]

Hepatitis B viral X protein alters the biological features and expressions of DNA repair enzymes in LO2 cells

Bin Cheng
Abstract Objectives: This study aimed at examining the effects of hepatitis B viral X protein (HBx) on the biological features and the expression of DNA repair enzymes in non-tumour human hepatic LO2 cells in vitro. Methods: The HBx gene was transfected into LO2 cells to establish stably HBx-expressing LO2/HBx cells. The morphological features, cell growth, cell cycle, apoptosis and colony formation of LO2/HBx cells, vector-transfected LO2/pcDNA3.1 cells and unmanipulated LO2 cells were studied. The expressions of DNA repair enzymes and DNA oxidative stress-related 8-hydroxydeoxyguanosine (8-OHdG) were determined by a real-time quantitative polymerase chain reaction assay and high-performance liquid chromatography coupled with electrochemical detection respectively. Results: In comparison with controls, significant morphological changes, faster growth, higher frequency of cells at the S phase, but lower at G0/G1 and M/G2 phases, a lower frequency of natural cell apoptosis and a higher percentage of colony formation were observed in the LO2/HBx cells. Furthermore, significantly higher levels of intracellular 8-OHdG and lower levels of human DNA glycosylase , (hMYH,) mRNA transcripts, but no significant change in human 8-oxoguanine DNA glycosylase 1 (hOGG1), were detected in the LO2/HBx cells. Conclusions: Our data indicated that HBx promoted growth and malignant transformation of non-tumour hepatic LO2 cells in vitro, which was associated with the downregulation of hMYH, expression and accumulation of mutagenic DNA adduct 8-OHdG. [source]

Biochemical markers of liver fibrosis and lymphocytic piecemeal necrosis in UDCA-treated patients with primary biliary cirrhosis

Christophe Corpechot
Abstract: Background/Aim: We have previously shown that the histological stage and severity of lymphocytic piecemeal necrosis (LPN) are independent predictive factors of cirrhosis development in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cirrhosis (PBC). Our aim during this study was to determine whether biochemical parameters classically used in PBC management and measured under UDCA could be considered as reliable surrogate markers for these histological prognostic indices in clinical practice. Method: The study included 153 patients with PBC who had undergone a control liver biopsy after 2 years of UDCA therapy. The relationships between histological and biological features were assessed by variance analysis and logistic regression. The diagnostic value of independent markers was assessed in terms of their sensitivity, specificity, positive predictive value (PPV) and negative value (NPV) and receiver-operating characteristic curves. Results: Two variables were independently associated with extensive fibrosis (i.e. advanced histological stages): serum levels of bilirubin and hyaluronic acid (HA). A fibrosis index ([bilirubin (,mol/l)/14]+[HA (,g/l)/143]) higher than 1.5 exhibited good PPV and specificity (>74%) but rather poor NPV and sensitivity (<64%) regarding a diagnosis of extensive fibrosis. The only independent marker of LPN was aspartate aminotransferase (AST) activity. AST activity of more than twice the upper limit of normal showed acceptable PPV (>70%) but very low sensitivity (<25%) for a diagnosis of LPN. Conclusions: Serum bilirubin and HA levels measured under UDCA therapy are of acceptable diagnostic value for extensive fibrosis, but none of the biochemical tests commonly employed in the management of PBC can be considered as surrogate markers of LPN. Taken together with our previous results, these findings suggest that liver biopsy may be necessary to screen UDCA-treated patients who might require additional therapies. [source]

Type III hereditary angio-oedema: clinical and biological features in a French cohort

ALLERGY, Issue 10 2010
V. Vitrat-Hincky
To cite this article: Vitrat-Hincky V, Gompel A, Dumestre-Perard C, Boccon-Gibod I, Drouet C, Cesbron JY, Lunardi J, Massot C, Bouillet L. Type III hereditary angio-oedema: clinical and biological features in a French cohort. Allergy 2010; 65: 1331,1336. Abstract Background:, Hereditary angio-oedema (HAE) has been associated with C1inhibitor deficiency. The first cases of type III HAE were described in patients with normal C1Inh antigenic protein level and function and normal C4 levels in 2000. This finding has been reported mostly in women with a family history and may be influenced by exogenous oestrogen exposure. Objectives:, The purpose of this article is to describe the clinical, biological and genetic characteristics of a French population suffering from type III HAE. Patients and Methods:, We conducted a retrospective analysis of angio-oedema (AE) cases seen in the National Reference Centre of AE between 2000 and 2009. Results:, We found 26 patients (from 15 unrelated families) with type III HAE. All but four were women and presented with typical AE attacks, exacerbated by pregnancy or oral contraceptives containing oestrogens (OC). We also found that 54.5% of women were worsened with oestrogen and 23% were oestrogen dependent. All patients improved on long-term prophylactic tranexamic acid treatment; some acute attacks improved with C1Inh concentrate infusion. All of the patients had normal C1Inh and C4 levels. C1Inh function was also normal, except in women receiving OC or during a pregnancy: transient, moderately low levels (32,74% of the normal range) were found in 18 patients tested (67%). No SERPING1 gene mutation was found. Six patients from three unrelated families were heterozygous for an F12 gene variant. Conclusion:, Diagnosis of type III HAE should be based on clinical (typical attacks, often hormonally influenced), laboratory (normal C1Inh antigenic protein) and genetic (F12 gene mutation) evidence. [source]

Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B

Seokjoon Lee
Abstract Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play essential roles in intracellular signal transduction by regulating the cellular level of tyrosine phosphorylation to control cell growth and differentiation, metabolism, cell migration, gene transcription, ion-channel activity, immune response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many human diseases, including cancer, diabetes, and obesity. Therefore, small molecular inhibitors of PTP1B can be promising drug candidates. Because of the structural homologies in many families of PTPs, it is a challenging task to find inhibitors specific to each PTP. Recent studies suggested that secondary binding pockets or peripheral binding sites around the conserved active site should be exploited to design novel potent and selective PTP1B inhibitors. In this review, we discuss the structural and biological features of small molecular PTP1B-specific inhibitors, with particular emphasis on small molecular inhibitors targeting PTP1B over the other PTPs that have been synthesized in the past 4 years. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 553,573, 2007 [source]

Comedonecrosis is an unfavorable marker in node-negative invasive breast carcinoma

Hiroshi Yagata
Breast carcinoma is usually accompanied by an invasive component with an intraductal component, and each component shows different morphological features. We evaluated whether the presence or absence of comedonecrosis is correlated with prognosis and biological features in node-negative invasive breast carcinoma. Ninety-four node-negative breast carcinomas with an intraductal component were classified into two types: comedo type (n = 36) showing comedonecrosis partly or extensively in the intraductal component, and non-comedo type (n = 58) showing either an absence or small foci of necrosis. The Kaplan,Meier method was used to calculate disease-free survival. Immunohistochemical examination for p53 and HER-2 was conducted on the comedo (n = 35) and non-comedo (n = 47) type tumor specimens. Disease-free survival was significantly shorter in the comedo type than in the non-comedo type (P = 0.019). The expression of p53 was observed in 16 (45.7%) of the 35 comedo type cases, but only in two (4.3%) of the 47 non-comedo type cases (P < 0.0001). HER-2 overexpression was observed in seven (20.0%) of the 35 comedo type cases, while none of the 47 non-comedo type cases overexpressed HER-2 (P < 0.0001). These results suggest that the presence of comedonecrosis may be predictive of an unfavorable prognosis with aggressive biological behavior in node-negative invasive breast carcinoma. [source]

Chromophobe renal cell carcinoma: Clinical, pathological and molecular biological aspects

Yoji Nagashima
Chromophobe renal cell carcinoma (RCC), a newly established subtype of renal neoplasm, is composed of tumor cells with characteristically cloudy, weakly eosinophilic and reticular cytoplasm. The tumor should be distinguished from the common clear cell RCC, because of the unique clinicopathological and molecular biological features. The tumor does not show gender bias. Patient ages are similar to those of clear cell RCC, but might occur in the 20- to 40-year-old age group. Grossly, the tumor tends to be beige in color, which is different from the yellowish color of common RCC. Electron microscopy and immunohistochemistry indicate the intercalated cell of the collecting duct as the cellular origin. Cytogenetic study shows non-random multiple chromosome loss, with mitochondrial DNA rearrangement. Alteration of the von Hippel,Lindau (VHL) gene, a cancer suppressor gene relating with clear cell RCC, has not yet been observed. In order to adopt the most appropriate treatment, including gene therapy, recognition and correct pathological diagnosis of chromophobe RCC are extremely important. [source]

Blast phase of essential thrombocythemia: A single center study,

Francesco Passamonti
Blast phase (BP) may occur as a late event in essential thrombocythemia (ET). This study includes 19patients with post-ET BP diagnosed and followed in a single institution. At BP, 63% of patients had leukocytosis (white blood cell count >10 × 109/L), 74% had anemia (hemoglobin value <10 g/dL), 74% had thrombocytopenia (platelet count <100 × 109/L), and 84% were over 65 years of age. Cytogenetic analysis was available in 10 patients: six had karyotype aberrations. According to cytogenetic-based risk stratification of de novo acute leukemia (AL), all patients had an unfavorable profile. JAK2 (V617F) mutational status was evaluated in five patients. In two of them, the JAK2 mutation was undetectable in blast cells (one with JAK2 -positive ET), whereas in three both granulocytes and blast cells displayed the mutation. Treatment of BP was patient-based according to the performance status and co-morbidities and consisted of palliation in 14 patients, and of induction of remission in five. Median survival was 2.3 months (range 0.2,22.3), irrespective of the treatment received. In conclusion, this study indicates that AL evolved from ET has unfavorable clinical and biological features. JAK2 (V617F)-positive ET may evolve in few instances into JAK2 -negative leukemia. The outcome of patients is poor whatever the treatment used. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

Results for 79 patients with neuroblastoma detected through mass screening at 6 months of age in a single institute

Abstract Background: In Japan, mass screening for neuroblastoma has been performed at 6 months of age to improve the prognosis of this condition for more than 20 years. In recent years, most neuroblastomas detected by mass screening were considered to have favorable biological features and sometimes tend to regress spontaneously. Methods: The authors established non-treated observation criteria in 1997 and criteria for observation of residual tumor after first-line chemotherapy in 1999, and have made an effort to reduce the intensity of medical treatment for neuroblastoma. The authors examined outcomes of 79 patients who were found in the Shizuoka neuroblastoma mass screening at 6 months of age and who received medical treatment or underwent observation in Shizuoka Children's Hospital, Shizuoka, Japan, between December 1981 and December 2004. Results: A total of 77 patients survived but the remaining two patients died from complications of medical treatment. None of the patients died due to progression of neuroblastoma. In the cases, non-treated observation was performed in 17. Of those, 12 patients are now under non-treated observation. Of their tumors, two have disappeared, nine have become smaller and another one has not change in size. Observation of residual tumor after first-line chemotherapy was performed in 15 cases, and three disappeared and the other 12 cases became smaller. Medical treatment-related complications were observed in 20 of 67 patients who received medical treatment, and 18 of the 20 patients were seen before establishing non-treated observation criteria. Conclusion: Non-treated observation and observation of residual tumor after first-line chemotherapy were useful to reduce medical treatment-related complications. [source]

Considerations in using tumor markers: what the psycho-oncologist needs to know

Debra L. Fertig
Tumor markers are measures of biological features of a cancer. By revealing important biological aspects of the tumor, tumor markers can be useful in staging patients, predicting cancer outcomes, and guiding treatments. The psychological consequences of using tumor markers are virtually unknown. In this review article, we draw on clinical studies involving the psychological impact of risk information, screening, prognostic information and surveillance of cancer. Such studies may be helpful in considering possible psychological reactions to tumor marker information in clinical practice. Copyright © 2001 John Wiley & Sons, Ltd. [source]

OCT4: biological functions and clinical applications as a marker of germ cell neoplasia

L Cheng
Abstract Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the gonads as well as in extragonadal sites, that share morphological patterns and an overall good prognosis, owing to their responsiveness to current surgical, chemotherapeutic, and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features because of their close relationships with normal embryonal development as demonstrated by the pluripotentiality of some undifferentiated GCT variants. The similarities between GCTs and normal germ cell development have made it possible to identify possible pathogenetic pathways in neoplastic transformation and progression of GCTs. Genotypic and immunophenotypic profiles of these tumours are also useful in establishing and narrowing the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development of commercially available OCT4-specific antibodies suitable for immunohistochemistry on paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry is an additional helpful marker both in the differential diagnosis of specific histological subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in managing patients known to be at high risk for the development of invasive GCTs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical Factor

E. Vibert
Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ,progression' of AFP was defined by >15 ,g/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 ,g/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 ,g/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness. [source]

A new synthesis: Resituating approaches to the evolution of human behaviour

Agustín Fuentes
Most anthropologists would agree that humans are simultaneously historical, biological, behavioral, and social. However, many researchers retain a relatively dualistic paradigm dividing anthropological questions into biological and/or social aspects. Many practitioners of Neo-Darwinian perspectives prioritize natural selection in all explanations of human evolution. Many other anthropologists refuse to acknowledge a significant role for biological features and biological histories in human action, sensation, and engagement. Both perspectives are misplaced. Incorporating emerging perspectives in evolutionary theory into the broader anthropological discourse may help discard simplistic dualisms and resituate our assessments of the evolution of human behavior. In this essay I review three major emergent themes in evolutionary theory; Multi-Inheritance Systems Theory, Developmental Systems Theory, and Niche Construction. I suggest, with one brief example, that placing these elements in transaction with other perspectives in anthropology might enhance the possibilities of assessing human evolution and behavior. [source]

Extragonadal germ cell tumors: relation to testicular neoplasia and management options

APMIS, Issue 1 2003
An unselected population of 635 consecutive extragonadal GCT patients (EGCT) treated between 1975 through 1996 at 11 cancer centers was retrospectively evaluated for clinical prognosis and biological features of this disease. Five hundred twenty-four patients (83%) had a nonseminomatous GCT, and 104 patients (16%) a seminomatous histology; 341 (54%) patients had a primary mediastinal EGCT, and 283 patients (45%) a retroperitoneal EGCT. Following platinum based induction chemotherapy±secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow up period: 19 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow up period: 29 months) are alive [p=0.0006]. In contrast, the overall survival rate for patients with seminomatous EGCT is 88% with no difference between patients with mediastinal or retroperitoneal tumor location (median follow up period: 49 months). Multivariate analysis revealed nonseminomatous histology, the presence of non-pulmonary visceral metastases, primary mediastinal GCT location, and elevated ,-HCG as independent prognostic factors for shorter survival. Sixteen patients (4.1%) developed a metachronous testicular cancer despite the use of platinum based chemotherapy. The cumulative risk of developing a MTC 10-years after a diagnosis of EGCT was 10.3% (95% CI=4.9 to 15.6%), but higher among patients with nonseminomatous EGCT (14.3%; 95% CI=6.7 to 21.9%) or retroperitoneal EGCT location (14.2%; 95% CI=5.6 to 22.8%) than among patients with seminomatous EGCT (1.4%; 95% CI=0.0 to 4.2) or mediastinal EGCT location (6.2%; 95% CI=0.1 to 12.2). After a median follow-up of 51 months (range=1 to 154 months), all 16 MTC patients were alive without disease. Patients with pure seminomatous EGCT histology have a long term chance of cure of almost 90% irrespective of the primary tumor site. Patients with mediastinal nonseminomas have a five-years survival rate of 45%. This outcome is clearly inferior compared to patients with nonseminomatous retroperitoneal primaries who have a five-year survival rate of 62%. [source]

Molecular chemical structure of barley proteins revealed by ultra-spatially resolved synchrotron light sourced FTIR microspectroscopy: Comparison of barley varieties

BIOPOLYMERS, Issue 4 2007
Peiqiang Yu
Abstract Barley protein structure affects the barley quality, fermentation, and degradation behavior in both humans and animals among other factors such as protein matrix. Publications show various biological differences among barley varieties such as Valier and Harrington, which have significantly different degradation behaviors. The objectives of this study were to reveal the molecular structure of barley protein, comparing various varieties (Dolly, Valier, Harrington, LP955, AC Metcalfe, and Sisler), and quantify protein structure profiles using Gaussian and Lorentzian methods of multi-component peak modeling by using the ultra-spatially resolved synchrotron light sourced Fourier transform infrared microspectroscopy (SFTIRM). The items of the protein molecular structure revealed included protein structure ,-helices, ,-sheets, and others such as ,-turns and random coils. The experiment was performed at the National Synchrotron Light Source in Brookhaven National Laboratory (BNL, US Department of Energy, NY). The results showed that with the SFTIRM, the molecular structure of barley protein could be revealed. Barley protein structures exhibited significant differences among the varieties in terms of proportion and ratio of model-fitted ,-helices, ,-sheets, and others. By using multi-component peaks modeling at protein amide I region of 1710,1576 cm,1, the results show that barley protein consisted of approximately 18,34% of ,-helices, 14,25% of ,-sheets, and 44,69% others. AC Metcalfe, Sisler, and LP955 consisted of higher (P < 0.05) proportions of ,-helices (30,34%) than Dolly and Valier (,-helices 18,23%). Harrington was in between which was 25%. For protein ,-sheets, AC Metcalfe, and LP955 consisted of higher proportions (22,25%) than Dolly and Valier (13,17%). Different barley varieties contained different ,-helix to ,-sheet ratios, ranging from 1.4 to 2.0, although the difference were insignificant (P > 0.05). The ratio of ,-helices to others (0.3 to 1.0, P < 0.05) and that of ,-sheets to others (0.2 to 0.8, P < 0.05) were different among the barley varieties. It needs to be pointed out that using a multi-peak modeling for protein structure analysis is only for making relative estimates and not exact determinations and only for the comparison purpose between varieties. The principal component analysis showed that protein amide I Fourier self-deconvolution spectra were different among the barley varieties, indicating that protein internal molecular structure differed. The above results demonstrate the potential of the SFTIRM to localize relatively pure protein areas in barley tissues and reveal protein molecular structure. The results indicated relative differences in protein structures among the barley varieties, which may partly explain the biological differences among the barley varieties. Further study is needed to understand the relationship between barley molecular chemical structure and biological features in terms of nutrient availability and digestive behavior. © 2006 Wiley Periodicals, Inc. Biopolymers 85:308,317, 2007. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [source]

Surface-directed assembly of cell-laden microgels,,

Yanan Du
Abstract Cell-laden microscale hydrogels (microgels) can be used as tissue building blocks and assembled to create 3D tissue constructs with well-defined microarchitecture. In this article, we present a bottom-up approach to achieve microgel assembly on a patterned surface. Driven by surface tension, the hydrophilic microgels can be assembled into well-defined shapes on a glass surface patterned with hydrophobic and hydrophilic regions. We found that the cuboidic microgels (,100,200,µm in width) could self-assemble into defined shapes with high fidelity to the surface patterns. The microgel assembly process was improved by increasing the hydrophilicity of the microgels and reducing the surface tension of the surrounding solution. The assembled microgels were stabilized by a secondary crosslinking step. Assembled microgels containing cells stained with different dyes were fabricated to demonstrate the application of this approach for engineering microscale tissue constructs containing multiple cell types. This bottom-up approach enables rapid fabrication of cell-laden microgel assemblies with pre-defined geometrical and biological features, which is easily scalable and can be potentially used in microscale tissue engineering applications. Biotechnol. Bioeng. 2010; 105: 655,662. © 2009 Wiley Periodicals, Inc. [source]