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At least 721 records · Page 40Linked to original sources
PubMed1994

Comparison of N-terminal affinity fusion domains: effect on expression level and product heterogeneity of recombinant restriction endonuclease EcoRV.

The influence of different N-terminal affinity fusion domains on the product heterogeneity of recombinant proteins expressed in Escherichia coli was investigated. N-Terminal extended forms of the restriction endonuclease EcoRV with either glutathione-S-transferase [GST], histidine hexapeptide [(His)6], or a combination of GST and (His)6 [GST-(His)6] were compared to native EcoRV with respect to expression level, susceptibility to inclusion body formation and protein fragmentation. Fingerprinting of product heterogeneity was done by using two-dimensional (2-D) non-equilibrium pH-gradient electrophoresis with subsequent immunoblotting. Fusion proteins containing GST were poorly expressed compared to native EcoRV. In addition, GST fusion proteins were highly susceptible to in-vivo aggregation and fragmentation and displayed more heterogeneity on 2-D immunoblots. However, the sole presence of oligohistidine at the N-terminus of EcoRV proved to be advantageous. Fragmentation of (His)6-EcoRV was not observed and 2-D immunoblots did not show heterogeneous forms of the recombinant protein. In addition, fusion of the histidine-hexapeptide to the N-terminus of native EcoRV increased the expression level of the recombinant protein twofold compared to native EcoRV. Inclusion body formation of the (His)6-EcoRV fusion protein was intensive when cells were grown at 37 degrees C but not at 30 degrees C. The advantage of oligohistidine fusion to EcoRV was finally demonstrated by purifying soluble (His)6-EcoRV in a single-step procedure from crude cell lysates using immobilized metal chelate affinity chromatography.

Biotechnology↗
PubMed1992

Endothelial heterogeneity and the acquired immunodeficiency syndrome: a paradigm for the pathogenesis of vascular disorders.

Vascular disorders comprise a wide range of diverse disease entities. Correspondingly, vessels, and even more so the endothelial which line them, show a remarkable extent of heterogeneous differentiation, e.g. between the blood vascular and lymphatic systems, along the length of the vascular trees, and in the microvascular beds of various organs. The most important morphologic criterion to discriminate between endothelia is continuity (continuous endothelial cell layer and well-formed basement membrane) versus discontinuity (intra- or intercellular gaps and/or reduced or missing basement membrane). Most blood vascular endothelia are of the continuous type, while most sinusoidal and lymphatic endothelia are discontinuous by these criteria. Antigen expression corroborates these morphologic data in that CD31, CD34, and 1F10 antigen are exclusively expressed in continuous endothelia, while MS-1 antigen is preferentially expressed in non-continuous sinusoidal endothelia. In contrast, no specific marker has as yet been described for lymphatic endothelia. Endothelial heterogeneity substantially contributes to the pathogenesis of vascular disorders. For example, in patients with acquired immunodeficiency syndrome the same infectious agent may cause either bacillary angiomatosis (a lobular capillary proliferation) or peliosis (sinusoidal dilatation, endothelial denudation, and development of blood-filled cysts) depending on whether the affected organs have predominantly continuous endothelia or noncontinuous sinusoidal endothelia. Moreover, in Kaposi's sarcoma, it is still an open question of whether the lesion is derived from blood vascular or lymphatic endothelia (Kaposi's sarcoma cells in situ do not express the von Willebrand factor+, PAL-E+, 1F10+ phenotype of mature, resting blood vascular endothelia). It is also unresolved how endothelia of either type may be differentially induced to dedifferentiate and how they are recruited into the lesion. Clearly, knowledge about endothelial heterogeneity is still too incomplete to identify the actual mechanisms and molecules that govern the pathogenesis of vascular disorders (including still others than those mentioned here such as atherosclerosis, diabetic angiopathy, and rheumatoid arthritis) affecting distinct endothelia. Further efforts in antigenic phenotyping and in cell and molecular biology of heterogeneously differentiated endothelia should be made to improve this state of affairs.

Angiomatosis, Bacillary↗
PubMed1991

Heterogeneity in ploidy and S-phase fraction in colorectal adenocarcinomas.

The heterogeneity in the DNA content was analysed in multiple biopsies from the surgical specimens in 77 cases of colonic and 46 cases of rectal adenocarcinomas. Frozen and unfixed tumour tissue was analysed with the flow cytometric technique. A total of 78/123 (63%) of all tumours displayed aneuploid stemlines in one or more pieces of tumour tissue; 45 were homogeneously aneuploid and 33 were heterogeneous, presenting both aneuploid and near-diploid samples. The remaining 45 tumours were homogeneously near-diploid. The heterogeneity in ploidy tended to be slightly higher if ten as compared with four samples from each tumour were analysed. Ploidy correlated to localization in the bowel and gender, but not to age, histopathological tumour stage, tumour differentiation or to the resectability rate for cure. The mean value of the S-phase fraction was 17% (range 7-31%) in the near-diploid and 14% (range 8-20%) in the aneuploid tumours. The range of the intratumoural variation was small for the DNA index (at most 5%) and high for the S-phase fraction (19% for near-diploid and 24% for aneuploid tumour pieces). Neither the mean value nor the heterogeneity in the DNA index and in the S-phase fraction displayed any correlation with the studied characteristics. In conclusion, the ploidy and the S-phase fraction varied considerably both within and between the tumours. As a consequence, multiple sampling is mandatory for a correct classification of colorectal adenocarcinomas based on the DNA content.

Adenocarcinoma↗
PubMed1991

An immunohistochemical study of endothelial cell heterogeneity in the rat: observations in "en face" Häutchen preparations.

"En face" sheets of endothelium, in which cellular spatial relationships were maintained, were prepared from proximal pulmonary and femoral arteries and aortae of the Wistar rat, in order to visualise patterns of heterogeneity in populations of endothelial cells. These preparations, termed Häutchen, were immunolabelled with antibodies to angiotensin II, endothelin and Factor-VIII-related antigen, and visualised by an avidin/biotin peroxidase complex. Clusters of cells, which accounted for approximately 30% of the total endothelial cell population, and which were positively immunostained for angiotensin II, were found perpendicular to the longitudinal axis of the aorta and femoral artery. Cells in the pulmonary artery were immunonegative for angiotensin II. The majority of cells in all three vessels were immunopositive for endothelin; groups of intensely stained cells were present in both the femoral artery and aorta, but not in the pulmonary artery. Immunoreactivity to Factor-VIII-related antigen was heterogeneous, with intensely stained amorphous patches of endothelial cells present in the femoral artery and aorta. Häutchen preparations present an opportunity for the investigation of endothelial cell heterogeneity, both within and between vessels; this may provide a basis for the interpretation of the heterogeneity of endothelium-dependent responses in vessels of differing origin.

Angiotensin II↗
PubMed1978

Heterogeneity in Chinese hamster ribosomal DNA.

A discrete heterogeneity has been detected in Chinese hamster ribosomal DNA after Eco R1 digestion of total DNA followed by a Southern transfer and hybridization with [125I]18S or [125I]28S ribosomal RNA. Digestion with Eco R1 produces three fragments, 4.3, 6.0 and 9.5 x 10(6) daltons respectively, which hybridize with 18S RNA. The smallest fragment also hybridizes with 28S RNA. Either length heterogeneity or sequence heterogeneity (i.e. presence of an additional Eco R1 site in some of the rDNA molecules) must be invoked to account for the two larger Eco R1 fragments that contain 18S but not 28S sequences. Eco R1 and Hind III maps, consistent with either length or sequence heterogeneity, are presented. The data at this time, however, do not distinguish between the two alternatives.

Animals↗
PubMed1994

Heterogeneity of mean sarcomere length in different fibres: effects on length range of active force production in rat muscle.

Isometric active length-force characteristics of rat semimembranosus lateralis muscles [rats, n = 6, body mass = 292 (SD 9) g] were recorded. Muscles were photographed during the force plateaus of the tetani to determine lengths of proximal, intermediate and distal fibres. From the mean number of sarcomeres in series in those fibres, mean sarcomere length at different muscle lengths was calculated. The heterogeneity of mean sarcomere lengths for each muscle was quantified according to the coefficient of variation of sarcomere lengths at muscle optimal length. Absolute muscle length changes were equal to fibre length changes. At all muscle lengths, mean sarcomere lengths in the distal fibres were significantly greater than those in proximal and intermediate fibres. The heterogeneity of mean sarcomere lengths augmented the length range of active force production between muscle optimal length and active slack length by about 38% to 43%. We concluded that in a muscle with a low degree of pennation, the heterogeneity of mean sarcomere lengths should be considered as a substantial contributor to the length range over which active force can be produced. In our experiment, the length ranges of active force production between optimal and slack length showed considerable differences (range 18.7-24.9 mm). The coefficient of correlation between length ranges and mean number of sarcomeres in series in various muscle regions was extremely low (r = -0.14) and not significant. The coefficient of correlation between length ranges and heterogeneity was high (r = 0.88) and significant. These data would suggest that muscles with a similar number of sarcomeres in series can exhibit quite different functional characteristics.

Animals↗
PubMedDate not supplied

Some aspects of cardiac heterogeneity.

It is remarkable that the heart, which obviously functions as a homogenous pump, shows such a high degree of heterogeneity. There are often contradictory or controversial results as far as transmural gradients are concerned (78). These discrepancies or inconsistencies, however, can at least in part be explained by species differences. Of particular interest is the heterogeneity that is due to the separation into two hearts. In view of the differences in the morphology and function of the left and right heart, it is surprising that the whole organ works in a rather homogenous fashion. In the past, the right heart has received not as much attention as the left heart. This is in particular true for small laboratory animals. It becomes more and more evident that compared to the left ventricle, the right ventricle reacts to various stimuli in a quantitatively different manner. More research on the right heart is therefore needed. Collectively, the data summarized in this article may be interpreted in that the heart not only works as a homogeneous unit, but may even benefit from the heterogeneity of its different parts or subunits under normal as well as under various pathophysiological conditions. Analysis of the processes involved in creating cardiac heterogeneity can provide new insights into the mechanism of adaptation of the heart.

Animals↗
PubMed1992

Surface heterogeneity of rat sperm during maturation.

Rat sperm isolated from the caput and caudal epididymis and the vas deferens were subjected to multiple partition in aqueous two-phase systems. The technique was used to reveal heterogeneity of a sperm population with respect to particular surface properties. Sperm from all three regions gave broad distributions indicative of heterogeneous cell populations. Greatest heterogeneity was observed for cauda sperm with caput and vas sperm producing similar distributions. Following multiple partition sperm from different regions of the distribution profiles were immunostained with three antibodies known to recognise maturation antigens. The results show that some antigens are acquired during epididymal transit whilst others are present throughout. The partition (surface heterogeneity) seen cannot therefore be explained solely by the distribution of the antigens recognized by 2D6, 6B2 and 3D5.

Animals↗
PubMed1993

Chromosome aberrations and cytogenetic intratumor heterogeneity in chondrosarcomas.

Clonal chromosome aberrations identified after short-term culture are presented for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9 tumors. The most frequent numerical anomalies were, in falling order of frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and 20. No recurrent structural rearrangement was found, but chromosome bands 5q13, 1q21, 7p11, and 20q11 were each involved in three different rearrangements. Karyotypic heterogeneity was assessed in two different ways: as the presence of more than one clone in one sample and as the presence of different clones in different samples from the same surgical specimen. Clonal karyotypic evolution was demonstrated in 6 of the 7 cases in which two or more samples could be investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity was found in only 5 of the 28 samples with aberrations. By comparing the incidences of the nonrandomly occurring aberrations in stemlines and sidelines in the heterogeneous tumors, it was possible to conclude that loss of chromosome 13 and rearrangement of band 5q13 were early events in the clonal evolution.

Adult↗
PubMed1985

Studies on the development of the charge heterogeneity of the influenza virus glycoproteins.

The heterogeneity in charge of the influenza virus glycoproteins, hemagglutinin (HA) and neuraminidase (NA) is retained, when glycosylation is inhibited by tunicamycin (TM) or 2-deoxyglucose (2-dg). This is in contrast to the charge heterogeneity of the G protein of vesicular stomatitis virus (VSV), which is mainly due to heterogeneous sulfation of the carbohydrate side chains and therefore is abolished by the above mentioned inhibitors of glycosylation. Thus, the charge heterogeneity of influenza virus glycoproteins might be attributable to some as yet unidentified modifications of the polypeptide backbone.

Animals↗
PubMed2005

Influence of electrophysiological heterogeneity on electrical stimulation in healthy and failing human hearts.

The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+-Ca2+ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.

Electric Countershock↗
PubMed1985

Regional, segmental, and temporal heterogeneity of cerebral vascular autoregulation.

Autoregulation of cerebral blood flow is heterogeneous in several ways: regional, segmental, and temporal. We have found regional heterogeneity of the autoregulatory response during both acute reductions and increases in systemic arterial pressure. Changes in blood flow are less in brain stem than in cerebrum during decreases and increases in cerebral perfusion pressure. Segmental heterogeneity of autoregulation has been demonstrated in two ways. Direct determination of segmental cerebral vascular resistance indicates that, while small cerebral vessels (less than 200 micron in diameter) make a major contribution to autoregulation during acute increases in pressure between 80 and 100 mm Hg, the role of large cerebral arteries (greater than 200 micron) becomes increasingly important to the autoregulatory response at pressures above 100 mm Hg. Measurement of changes in diameter of pial vessels has shown that, during acute hypotension, autoregulation occurs predominantly in small resistance vessels (less than 100 micron). Finally, there is temporal heterogeneity of autoregulation. Sudden increases in arterial pressure produce transient increases in blood flow, which are not observed under steady-state conditions. In addition, the blood-brain barrier is more susceptible to hypertensive disruption after rapid, compared to step-wise, increases in arterial pressure. Thus, when investigating cerebral vascular autoregulation, regional, segmental, and temporal differences in the autoregulatory response must be taken into consideration.

Animals↗
PubMed1991

Heterogeneity in antigenic expression and radiosensitivity in human colon carcinoma cell lines.

A panel of human colon carcinoma cell lines were characterized regarding both antigenic heterogeneity and variations in radiosensitivity. Monoclonal antibodies were used to study the expression of carcinoembryonic antigen (CEA), gastrointestinal cancer antigen (GICA or CA 19-9) and carcinoma-associated antigen (CA-50). Radiosensitivity was studied with the clonogenic survival technique. Three cell lines, LS 174T, HCTC, and SW 1116 stained positive for all three antigens. HT-29 was positive for CA 19-9 and CA-50 whereas Caco-2 was positive for CEA and CA 19-9. The cell lines SW 620 and LIM 1215 only stained positive for one of the antigens, CA-50 and CEA, respectively. In nearly all positive cases the stainings were very heterogeneous with mixtures of positive and negative cells. One exception was the HCTC cells which stained homogeneously for the CA 19-9 and CA-50 antigens. The neuroendocrinelike COLO 320 cells were negative in all cases. The radiosensitivity varied strongly between the cell lines with Dq-values between 0.8 and 1.9, extrapolation numbers between 2.0 and 4.7, Do-values between 1.1 and 2.8. The surviving fraction at 2 Gy varied between 0.3 and 0.7 with HCTC as the most radiosensitive and HT-29 as the most radioresistant cell line. Thus, there were differences in antigenic expression and intrinsic radiosensitivity between the cell-lines and antigenic heterogeneities within each cell line. The analyzed panel of cell lines will be valuable in studies of dose-effect relations for monoclonal antibodies labeled with toxic radionuclides simulating both antigenic heterogeneity and variations in radiosensitivity.

Adenocarcinoma↗
PubMed1999

New perspectives in the functional role of GABA(A) channel heterogeneity.

Gamma-aminobutyric acid A (GABA(A)) channels responsible for inhibitory synaptic transmission possess a consistent heterogeneity of structure in terms of distinct constitutive subunits. During the past 10 years, considerable progress has been made in understanding the magnitude of this large diversity. Structural requirements for clinically important drugs such as benzodiazepines and barbiturates have been elucidated, and the anatomical distribution in distinct neuronal populations and the developmental profiles of individual subunits have been elucidated with various techniques. However, the relevance of subunit heterogeneity to synaptic transmission is still largely lacking. Recently, substantial progress has been achieved in understanding the crucial role of desensitization as a molecular determinant in defining the duration and frequency responses of inhibitory synaptic transmission. This development, together with a combination of different experimental approaches, including patch-clamp recordings and ultrafast agonist applications in brain slices and mammalian cells expressing recombinant GABA(A) receptor, has begun to shed light on a possible role for subunit composition of synaptic receptors in shaping the physiological characteristics of synaptic transmission. Nowhere else in the central nervous system is the anatomical and developmental profile of GABA receptor heterogeneity as well understood as it is in the cerebellum. This review summarizes advances in the understanding of functional correlates to subunit heterogeneity in the cerebellum relevant for inhibitory synaptic function.

Animals↗
PubMed2006

EEG human head modelling based on heterogeneous tissue conductivity.

This paper studies the effect of heterogeneous tissue conductivity in a human head model for the EEG forward problem. Firstly, the tissue heterogeneity in conductivity was characterised from measured data in the literature. Then a method was developed to include this feature in modelling. Finally, the effect of tissue heterogeneity on EEG signals was studied. Based on these studies the paper concludes that the inclusion of tissue heterogeneity is significant in accurate head modelling for the EEG problem.

Action Potentials↗
PubMed1991

Heterogeneity of serum prolactin in patients with menstrual disorder in conjunction with hyperthyroxinemia.

Since the secretion of PRL is regulated by the hypothalamic-pituitary axis, an increase in large molecular size PRL in the serum is most likely due to secretion by the pituitary itself. The present study was performed to investigate the possible occurrence of PRL heterogeneity in 128 subjects with menstrual disorder in conjunction with hyperthyroxinemia (88 with untreated Graves' disease, 40 with subacute thyroiditis) and 50 age- and sex-matched healthy controls. All 128 patients in this study were suffering from amenorrhea or oligomenorrhea at the time of their initial visit. PRL heterogeneity was found in the sera of 5 of 88 (5.7%) patients with untreated Graves' disease, in 2 of 40 (5.0%) patients with subacute thyroiditis, but in none of the normal controls. PRL heterogeneity remained essentially unchanged in patients with Graves' disease over 6 months of treatment; however, in patients with subacute thyroiditis, either big-big PRL or big PRL decreased significantly along with a corresponding increase in little PRL associated with recovery from the illness within 6 months. The menstrual disorders in all patients were restored to normal after restoration to a euthyroid state. The underlying cause of the occurrence of PRL heterogeneity in patients with menstrual disorder in conjunction with hyperthyroxinemia is not known.

Adolescent↗
PubMed2006

Effect of heterogeneity on the quantitative determination of trace elements in concrete.

Laser-induced breakdown spectroscopy has been used for quantitative measurement of trace elements, e.g. sulfur and chlorine, in concrete. Chloride and sulfate ions have a large effect on the durability of concrete structures, and quantitative measurement is important for condition assessment and quality assurance. Concrete is a highly heterogeneous material in composition and grain-size distribution, i.e. the spatial distribution of elements. Calibration plots were determined by use of laboratory-made reference samples consisting of pressings of cement powder, hydrated cement, cement mortar, and concrete, in which the heterogeneity of the material is increasing because of the aggregates. Coarse aggregate and cement paste are distinguishable by the intensity of the Ca spectral lines. More advanced evaluation is necessary to account for the effect of the fine aggregate. The three series of reference samples enable systematic study of the effects of heterogeneity on spectral intensity, signal fluctuation, uncertainty, and limits of detection. Spatially resolved measurements and many spectra enable statistical evaluation of the data. The heterogeneity has an effect on measurement of the sulfur and chlorine content, because both occur mainly in the cement matrix. Critical chloride concentrations are approximately 0.04% (m/m). The chlorine spectral line at 837.6 nm is evaluated. The natural sulfur content of concrete is approximately 0.1% (m/m). The spectral line at 921.3 nm is evaluated. One future application may be simultaneous determination of the amount of damaging trace elements and the cement content of the concrete.

Journal Article↗
PubMed2001

Structural heterogeneity of blue copper proteins: an EPR study of amicyanin and of wild-type and Cys3Ala/Cys26Ala mutant azurin.

A comparative investigation of the effects of cooling rate and solvent physicochemical properties on the structural heterogeneity of wild-type and disulfide bond depleted azurin (Cys3Ala/Cys26Ala) and of amicyanin has been performed by EPR spectroscopy and computer simulation. By describing the spectral features of the EPR spectra in terms of Gaussian distributions of the components of the g and A tensors of the spin Hamiltonian, we have shown that either the cooling rate or the solvent composition affect the structural heterogeneity of the proteins. Such a heterogeneity has been quantified by the standard deviations sigmag and sigmaA of the parallel components of the axially symmetric tensors. In particular, both parameters become smaller after the slow cooling cycle; such a reduction is more significant when glycerol is added as cosolvent to the protein solutions. The comparison of the deltag and sigmaA values found, for the copper proteins investigated, highlights that the reduction is more marked in the azurins compared to amicyanin and that the Cys3Ala/Cys26Ala azurin mutant has a structural heterogeneity lower than that shown by the wild-type protein. The remarkable similarity of the copper coordination sphere of the proteins suggests a more rigid structure of the azurin protein matrix in the absence of the disulfide bridge compared to wild-type azurin and of amicyanin with respect to both forms of azurin. The former result establishes an important role for the -SS- bond in modulating the flexibility of wild-type azurin.

Alanine↗