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At least 55 records · Page 3Linked to original sources
PubMed1987

Muscarinic receptor heterogeneity in rat central nervous system. II. Brain receptors labeled by [3H]oxotremorine-M correspond to heterogeneous M2 receptors with very high affinity for agonists.

We compared the binding characteristics of muscarinic receptors labeled by [3H]oxotremorine-M ([3H]oxo-M) in homogenates of brain cortex and heart from rat. In both tissues [3H]oxo-M bound, with the same KD (6.5 nM), to a fraction of the receptors labeled by [3H]-N-methylscopolamine ([3H]NMS). This [3H]oxo-M receptor population represented, respectively, 15-20% and 35-40% of the total number of [3H]NMS receptors in cortex and heart. The three unlabeled agonists oxotremorine, carbamylcholine, and pilocarpine, when tested in competition with [3H]oxo-M, displayed a homogeneous super high affinity toward [3H]oxo-M-labeled receptors, and were unable to discriminate between brain and heart receptors labeled by [3H]oxo-M. By contrast, selective muscarinic antagonists showed some selectivity for either brain or heart [3H]oxo-M-labeled receptors. We analyzed competition curves between [3H]oxo-M and secoverine, pirenzepine, AF-DX 116, dicyclomine, or gallamine, assuming the existence of one or two receptor subclasses. Heart muscarinic receptors labeled by [3H]oxo-M were homogeneous M2 receptors of the C type with very low affinity for pirenzepine (Ki = 400 nM). Brain [3H]oxo-M-labeled receptors were heterogeneous receptors, with 30% (the B type) having a higher affinity for dicyclomine and a lower affinity for AF-DX 116 and gallamine than cardiac receptors, whereas the remaining 70% (the C type) showed "cardiac-like" binding properties. Both [3H]oxo-M-labeled subtypes in cortex homogenates had a low affinity for pirenzepine, indicating that [3H]oxo-M labeled only B and C (M2) receptors in this tissue. GTP inhibited completely [3H]oxo-M binding in heart homogenates with an IC50 at 300 nM. In cortex homogenates, GTP showed the same potency, but its efficacy was much lower (with only 30% maximal inhibition). [3H]oxo-M dissociation kinetics were monophasic in heart homogenates and biphasic in cortex homogenates. [3H]oxo-M dissociation from both tissues was slowed by gallamine and d-tubocurarine and accelerated by GTP. We found no correlation between B versus C [3H]oxo-M receptors, GTP-sensitive versus GTP-insensitive receptors, and rapidly versus slowly dissociating receptors, suggesting that [3H] oxo-M labeled a large variety of muscarinic receptor-regulatory protein complexes, all having an SH affinity for agonists.

Animals↗
PubMed1981

The heterogenization of tumour cells with tuberculin. II. Studies of the antigenicity of tuberculin-heterogenized murine tumour cells in syngeneic BCG positive and BCG negative mice.

The possibility of enhancing the antigenicity of tumour cells by chemically attaching purified protein derivative (PPD) of tubercle bacillus as an immunogenic carrier determinant into the tumour cell surface has been explored in these studies. It was observed that multiple immunizations with PPD-coupled tumour cells did potentiate a marked anti-rumour response even to tumours that were very weakly antigenic. Moreover, such immunizations could be used to retard the growth of tumours in previously unimmunized animals. An attempt has been made to elucidate the important factors involved when PPD heterogenized tumour cells are used for immunization.

Animals↗
PubMed1982

Antigenic heterogeneity of human colorectal cancer cell lines analyzed by a panel of monoclonal antibodies. I. Heterogeneous expression of Ia-like and HLA-like antigenic determinants.

The pattern of reactivity of 10 monoclonal antibodies (MCA) developed against human lymphoid leukemia cells and tested with human T-cells, B-cells, as well T-lymphoma and B-lymphoma cell lines suggested that six of them detect la-like determinants, three detect HLA-like determinants, and the remaining one detects a non-Ia B-cell antigen. With the use of three binding assays, the six MCA that appeared to detect Ia-like determinants reacted strongly with the human colorectal cancer cell (CCC) line LoVo, and none of the three MCA that reacted with HLA-like determinants reacted with this cell line. Immunoprecipitation and polyacrylamide gel electrophoresis analysis confirmed the apparent specificities of the MCA for Ia-like and HLA molecules, demonstrated the presence of Ia-like molecules in LoVo, and failed to detect HLA in these cells. The cellular enzyme-linked immunosorbent assay was used for the testing of our anti-Ia and anti-HLA MCA with 15 other CCC lines. Marked heterogeneity was found in the expression of different Ia-like and HLA determinants defined by different or overlapping subsets of MCA, which suggested that these determinants might be present on different molecules or that different conformations of the same molecules exist in various CCC lines. Analysis of the surface phenotype of subclones of LoVo cells revealed the presence of stable variant cell subpopulations, which lost reactivity with four out of six of the anti-Ia-like MCA but retained at least one Ia-like molecule recognized by two of our MCA. All of the subclones maintained the HLA-negative phenotype. The possible immunologic and diagnostic consequences of the presence or absence of Ia-like or HLA markers on nonlymphoid tumor cells are discussed.

Antibodies, Monoclonal↗
PubMed1983

Characterization of metastatic heterogeneity among subpopulations of a single mouse mammary tumor: heterogeneity in phenotypic stability.

The frequency of metastasis formed by tumor cells injected into lateral tail veins, mammary fatpads, or the subcutis are described for eight subpopulations of a single, spontaneously arising BALB/cfC3H mouse mammary tumor. These subpopulations display a spectrum of metastatic behavior from all three injection sites. The proportion of animals with metastases does not depend upon the site of primary tumor growth (i.e., mammary fatpad versus subcutis). One subpopulation can grow as lung nodules after intravenous injection but is only poorly metastatic from subcutaneous or fatpad implants. Heterogeneity among the subpopulations in the stability of the metastatic phenotype is evident. Although most of the subpopulations and their clones remained stable for periods of 2-5 years, one subpopulation rapidly lost metastatic ability within 3 months and another gradually became more metastatic over 2 years.

Animals↗
PubMed1998

Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity.

Maturity-onset diabetes of the young (MODY) can be defined by the clinical characteristics of early-onset Type 2 (non-insulin-dependent) diabetes and autosomal dominant inheritance. Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), hepatic nuclear factor 4 alpha (HNF4alpha) and insulin promoter [corrected] factor 1 (IPF1). In white Caucasians it is now possible to define the gene in most patients with a clinical diagnosis of MODY. Each gene involved in MODY has its own specific clinical and physiological characteristics. Patients with mutations of the glucokinase gene have mild fasting hyperglycaemia throughout life, and rarely require medication or develop microvascular complications. The principle pathophysiology is stable beta-cell dysfunction characterized by reduced sensing of glucose by the pancreas. Patients with mutations in HNF1alpha have normal glucose tolerance in early childhood and usually present with symptomatic diabetes in their late teens or early adulthood. They show increasing hyperglycaemia and treatment requirements with frequent microvascular complications. The underlying defect is progressive beta-cell failure, with the early lesion characterized by failure to increase insulin secretion with increasing glucose levels. Patients with HNF4alpha and IPF1 mutations show a similar clinical picture to HNF1alpha although diabetes may be diagnosed later. There are other patients with MODY in whom the genetic defect is still unknown. Molecular genetic testing in patients with diabetes offers the possibility of making a firm diagnosis of MODY and allows prediction of the future clinical course. The role of predictive testing in non-diabetic subjects within families is uncertain at present. Preliminary evidence suggests that maintaining insulin sensitivity by avoiding obesity and regular physical exercise may help delay the onset of diabetes.

Adolescent↗
PubMed1997

Genomic heterogeneity of small ruminant lentiviruses: existence of heterogeneous populations in sheep and of the same lentiviral genotypes in sheep and goats.

We have recently shown that French small ruminant lentiviruses (SRLV) from sheep are more similar to Caprine Arthritis Encephalitis Virus (CAEV) than to visna maedi virus (VMV) in a conserved region of the pol gene. To extend these results, we have examined sequences from a variable region of the env gene in French SRLV. We found that they were nearly equally distant from both CAEV and VMV strains, suggesting a considerable divergence since the initial introduction of the virus. Analysis of separate clones from individual animals showed that some carry a population of variant viruses. The study of further pol gene sequences from both goats and sheep suggests that viral variants show little or no host species specificity. A phylogenetic tree of pol gene sequences confirmed the presence of a novel genotype of SRLV in France.

Amino Acid Sequence↗
PubMed2001

Heterogeneous asymmetric reactions. Part 24. Heterogeneous catalytic enantioselective hydrogenation of the C==N group over cinchona alkaloid modified palladium catalyst.

The enantioselective hydrogenation of C==N-C group containing compounds over modified metal catalysts is as yet an uninvestigated research area. This work contains results obtained on the hydrogenation of 1-pyrroline-2-carboxylate esters and sodium salt over cinchona alkaloid-modified alumina-supported Pd catalyst. The effect of the reaction parameters and the structure of the alkaloid molecule on hydrogenation rate and enantioselectivity allowed us to assume that on the catalyst surface only a weak interaction exists between the modifier and the substrate, resulting in the low enantiomeric excesses (up to 20%) obtainable in these reactions.

Catalysis↗
PubMed1985

Heterogeneity of lysosomal enzymes in cultured normal and sialidosis type II human fibroblasts and the effect of ammonium chloride on this heterogeneity.

Lysosomal enzymes of human skin fibroblasts sediment in a Percoll gradient with major peaks at 1.05 and 1.10 g cm-3. The distribution of enzyme activity between the two peaks is dependent on growth state of the cells. Sialidosis Type II fibroblasts show a normal distribution pattern. NH4Cl stimulates enzyme secretion and de novo enzyme synthesis.

Ammonium Chloride↗
PubMed1988

Conformation heterogeneity in proteins as an origin of heterogeneous fluorescence decays, illustrated by native and denatured ribonuclease T1.

We examined the frequency-domain intensity decays of the intrinsic tryptophan fluorescence (Trp-59) from ribonuclease T1 (EC 3.1.27.3) (RNAase T1). At pH 5.5 in the native state (below 30 degrees C), the intensity decay of the single tryptophan residue is a single-exponential process. Conditions which result in protein unfolding were found to induce more complex intensity decays. At temperatures above 40 degrees C, or in the presence of guanidine hydrochloride, the intensity decays became obviously double exponential. In general, the main effect of temperature or guanidine was to induce a second subnanosecond component in the intensity decay. The increased complexity of the decays could not be explained by a unimodal distribution of decay times. These results indicate that conformational dispersion of protein structure can be one origin of the multi-exponential decays which are generally observed for protein fluorescence.

Exoribonucleases↗
PubMed1993

Heterogeneity of type-II interleukin-1 receptors. Heterogeneity of B-cell interleukin-1 binding created by dimerization of type-II interleukin-1 receptors.

The binding of IL-1 alpha and IL-1 beta to two human lymphoblastoid B-cell lines, Raji and RPMI 1788, was compared with binding to the murine T-cell line, EL4. Dramatic differences in IL-1 binding were observed. Both human B-cell lines bound much less IL-1 alpha than IL-1 beta, expressed 5-10 times more receptors per cell for IL-1 beta than did the EL4 cell line, and demonstrated a large difference in the ability of IL-1 alpha to compete with IL-1 beta for binding. The B-cell lines demonstrated a low number of high-affinity IL-1 alpha receptors and a large number of IL-1 alpha receptors with a much lower affinity. Inhibition studies demonstrated that only IL-1 beta could compete for the binding of radiolabeled IL-1 beta to the B-cell IL-1R. Furthermore, SDS-PAGE analyses of lysates of the B-cell lines that had been affinity cross-linked with 125I-IL-1 alpha revealed two bands corresponding to IL-1R structures of 60 and 110 kD. These results coupled with a nonequilibrium binding study suggested a dimerization of a common type-II IL-1R polypeptide, the dimer being responsible for the high-affinity IL-1 alpha-binding site of the B-cell lines.

Animals↗
PubMed2004

Correlation between lifetime heterogeneity and kinetics heterogeneity during chlorophyll fluorescence induction in leaves: 1. Mono-frequency phase and modulation analysis reveals a conformational change of a PSII pigment complex during the IP thermal phase.

The relationship between the fluorescence lifetime (tau) and yield (Phi) obtained in phase and modulation fluorometry at 54 MHz during the chlorophyll fluorescence induction in dark-adapted leaves under low actinic light has been investigated. Three typical phases have been identified: (i) linear during the OI photochemical rise, (ii) convex curvature during the subsequent IP thermal rise, and (iii) linear during the PS slow decay. A similar relationship has been obtained in the fluorescence induction for the fluorescence yield measured at 685 nm plotted versus the fluorescence yield measured at 735 nm. A spectrally resolved analysis shows that the curvature of the tau-Phi relationship is not due to chlorophyll fluorescence reabsorption effects. Several other hypotheses are discussed and we conclude that the curvature of the tau-Phi relationship is due to a variable and transitory nonphotochemical quenching. We tentatively propose that this quenching results from a conformational change of a pigment-protein complex of Photosystem II core antenna during the IP phase and could explain both spectral and temporal transitory changes of the fluorescence. A variable blue shift of the 685 nm peak of the fluorescence spectrum during the IP phase has been observed, supporting this hypothesis.

Adaptation, Physiological↗