scholarly journals IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide

1997 ◽  
Vol 43 (12) ◽  
pp. 2312-2317 ◽  
Author(s):  
Andrea Griesmacher ◽  
Günter Weigel ◽  
Gernot Seebacher ◽  
Mathias M Müller
Keyword(s):  
Human Plasma ◽  
Mycophenolic Acid ◽  
Human Lymphocytes ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Inhibitory Effects ◽  
Mediated Effects ◽  
Transplant Patients ◽  
Mycophenolic Acid Glucuronide

Abstract Inosine 5′-monophosphate dehydrogenase (IMP-DH) activities were measured in human lymphocytes (exhibiting type I IMP-DH activity) and human lymphoblasts (exhibiting type II IMP-DH activity) in the presence of various amounts of mycophenolic acid (MPA) (0–20 μmol/L) and MPA glucuronide (MPAG) (0–200 μmol/L). Moreover, the influences of human serum albumin (HSA) and human plasma on the MPA- and MPAG-mediated effects were investigated. In the presence of water, 2.5 μmol/L MPA decreased the IMP-DH activity measured in lymphocytes by 60%, whereas in lymphoblasts a 80% inhibition was detectable. In the presence of ≥10 μmol/L MPA, lymphocytic as well as lymphoblastic IMP-DH activities were reduced in a similar manner. The concentration of MPAG required for 50% inhibition was for both cell types >25 μmol/L and <50 μmol/L, respectively. MPAG (200 μmol/L) reduced lymphocytic as well as lymphoblastic IMP-DH activity by ∼80%. With 100 g/L HSA or human plasma as diluent, the inhibitory effects of MPA and MPAG were significantly (P <0.05) diminished, whereas HSA concentrations ≤25 g/L only slightly influenced the inhibition of IMP-DH activity by MPA and MPAG. In summary, it can be clearly demonstrated that not only MPA but also MPAG contributes to the inhibition of both IMP-DH isoenzymes, which might be relevant for the immunosuppressive properties of mycophenolate mofetil in transplant patients.

Immunological Determined Plasminogen Groups And Its Possible Biological Relevance

1981 ◽  
Author(s):  
V Sachs ◽  
R Dörner ◽  
E Szirmai
Keyword(s):  
Human Plasma ◽  
Type I ◽  
Type Ii ◽  
Precipitation Line ◽  
Gene Frequencies ◽  
Type Iii ◽  
Different Types ◽  
Human Plasminogen ◽  
Gel Diffusion ◽  
Good Agreement

Anti human plasminogen sera of the rabbit precipitate human plasma in the agar gel diffusion test by means of intra-basin absorption with plasminogenfree human plasma with three different types: type I is represented by one strong precipitation line, type II by two lines, a big one and a small one, and type III by three slight but distinct lines. The following frequencies of the different types have been observed in a sample of 516 human plasmas: type I 65%, type II 33% and type III 2%. Suppose the types are phenotypical groups of a diallelic system where the types I and III represent the homozygous genotypes and the type II the heterozygous the estimated gene frequencies are in good agreement with the expected values. There is also a good agreement of the distribution of plasminogen groups determined by electrofocussing from RAUM et al. and HOBART. The plasminogen groups possibly may have also a biological meaning because the plasmas of type III always have a lesser fibrinolytic activity than the plasmas of the other types.

HPLC determination of mycophenolic acid and mycophenolic acid glucuronide in human plasma with hybrid material

2004 ◽  
Vol 36 (3) ◽  
pp. 649-651 ◽  
Author(s):  
Magali Bolon ◽  
Laetitia Jeanpierre ◽  
Mirna El Barkil ◽  
Karim Chelbi ◽  
Martine Sauviat ◽  
...  
Keyword(s):  
Human Plasma ◽  
Mycophenolic Acid ◽  
Hybrid Material ◽  
Hplc Determination ◽  
Mycophenolic Acid Glucuronide

scholarly journals Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8.

1989 ◽  
Vol 9 (4) ◽  
pp. 1553-1565 ◽  
Author(s):  
D A Kulesh ◽  
G Ceceña ◽  
Y M Darmon ◽  
M Vasseur ◽  
R G Oshima
Keyword(s):  
Cell Types ◽  
Immunofluorescent Staining ◽  
Type I ◽  
Type Ii ◽  
Tail Domain ◽  
Proteolytic System ◽  
L Cells ◽  
Adult Mice ◽  
3T3 Fibroblasts ◽  
Keratin Filament

Human keratin 18 (K18) and keratin 8 (K8) and their mouse homologs, Endo B and Endo A, respectively, are expressed in adult mice primarily in a variety of simple epithelial cell types in which they are normally found in equal amounts within the intermediate filament cytoskeleton. Expression of K18 alone in mouse L cells or NIH 3T3 fibroblasts from either the gene or a cDNA expression vector results in K18 protein which is degraded relatively rapidly without the formation of filaments. A K8 cDNA containing all coding sequences was isolated and expressed in mouse fibroblasts either singly or in combination with K18. Immunoprecipitation of stably transfected L cells revealed that when K8 was expressed alone, it was degraded in a fashion similar to that seen previously for K18. However, expression of K8 in fibroblasts that also expressed K18 resulted in stabilization of both K18 and K8. Immunofluorescent staining revealed typical keratin filament organization in such cells. Thus, expression of a type I and a type II keratin was found to be both necessary and sufficient for formation of keratin filaments within fibroblasts. To determine whether a similar proteolytic system responsible for the degradation of K18 in fibroblasts also exists in simple epithelial cells which normally express a type I and a type II keratin, a mutant, truncated K18 protein missing the carboxy-terminal tail domain and a conserved region of the central, alpha-helical rod domain was expressed in mouse parietal endodermal cells. This resulted in destabilization of endogenous Endo A and Endo B and inhibition of the formation of typical keratin filament structures. Therefore, cells that normally express keratins contain a proteolytic system similar to that found in experimentally manipulated fibroblasts which degrades keratin proteins not found in their normal polymerized state.

scholarly journals Nodal signalling and apoptosis

Reproduction ◽  
2007 ◽  
Vol 133 (5) ◽  
pp. 847-853 ◽  
Author(s):  
Hongmei Wang ◽  
Benjamin K Tsang
Keyword(s):  
Transforming Growth Factor ◽  
Biological Effects ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Human Trophoblast ◽  
Adult Tissues ◽  
Ovarian Epithelial Cancer ◽  
Smad Proteins

Nodal, a member of the transforming growth factor β family, was first cloned from a 7.5 day post-coitum mouse embryo cDNA library. Nodal exerts its biological effects by signalling through its types I and II serine/threonine kinase receptor complex and intracellular Smad proteins. The type II receptors for Nodal are Activin type II receptors ActRIIA and ActRIIB, whereas the putative type I receptors are Activin receptor like kinase (ALK) 4 and ALK7. The main Smad proteins involved in Nodal signalling are Smad2 and Smad3. Studies of Nodal in adult tissues indicate that it is pro-apoptotic in rat ovarian granulosa cells, human trophoblast cells and human ovarian epithelial cancer cells and is growth inhibitory in the latter two cell types. This review summarises the progress made on the functions of Nodal in the apoptosis of adult tissues, especially in the ovary and placenta.

Computer Reconstructions of Normal Human Alveoli From Serial Sections

1985 ◽  
Vol 43 ◽  
pp. 312-313
Author(s):  
Saundra C. Parra ◽  
Ricky Burnette ◽  
Timothy Takaro
Keyword(s):  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Serial Sections ◽  
Single Plane ◽  
Random Sections ◽  
Normal Human ◽  
Connective Tissue Matrix ◽  
Different Cell Types ◽  
Tissue Matrix

Portions of two adjacent normal human alveoli were reconstructed from serial sections in order to examine normal alveolar organization, including anatomical relationships among the different cell types, the connective tissue matrix and gaps in the alveolar septum. Computer reconstructions were prepared from montaged electron micrographs of serial sections. Rotation of these reconstructions in the x, y or z axes allowed examination of the alveoli from many different aspects other than the actual plane of sectioning. Anatomical relationships “between Type I and Type II epithelial cells, alveolar macrophages, and pores of Kohn that could not he deduced from a single plane of the section (random sections) were revealed.

Vestibular Type I and Type II Hair Cells. 1: Morphometric Identification in the Pigeon and Gerbil

1997 ◽  
Vol 7 (5) ◽  
pp. 393-406
Author(s):  
Anthony J. Ricci ◽  
Katherine J. Rennie ◽  
Stephen L. Cochran ◽  
Golda A. Kevetter ◽  
Manning J. Correia
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Cell Types ◽  
Type I ◽  
Type Ii ◽  
Body Width ◽  
Fixed Tissue ◽  
Neck Width ◽  
I Cells ◽  
Plate Width

Classically, type I and type II vestibular hair cells have been defined by their afferent innervation patterns. Little quantitative information exists on the intrinsic morphometric differences between hair cell types. Data presented here define a quantitative method for distinguishing hair cell types based on the morphometric properties of the hair cell’s neck region. The method is based initially on fixed histological sections, where hair cell types were identified by innervation pattern, type I cells having an afferent calyx. Cells were viewed using light microscopy, images were digitized, and measurements were made of the cell body width, the cuticular plate width, and the neck width. A plot of the ratio of the neck width to cuticular plate width (NPR) versus the ratio of the neck width to the body width (NBR) established four quadrants based on the best separation of type I and type II hair cells. The combination of the two variables made the accuracy of predicting either type I or type II hair cells greater than 90%. Statistical cluster analysis confirmed the quadrant separation. Similar analysis was performed on dissociated hair cells from semicircular canal, utricle, and lagena, giving results statistically similar to those of the fixed tissue. Additional comparisons were made between fixed tissue and isolated hair cells as well as across species (pigeon and gerbil) and between end organs (semicircular canal, utricle, and lagena). In each case, the same morphometric boundaries could be used to establish four quadrants, where quadrant 1 was predominantly type I cells and quadrant 3 was almost exclusively type II hair cells. The quadrant separations were confirmed statistically by cluster analysis. These data demonstrate that there are intrinsic morphometric differences between type I and type II hair cells and that these differences can be maintained when the hair cells are dissociated from their respective epithelia.

scholarly journals Induction of Human Liver X Receptor α Gene Expression Via an Autoregulatory Loop Mechanism

2002 ◽  
Vol 16 (3) ◽  
pp. 506-514 ◽  
Author(s):  
Yu Li ◽  
Charles Bolten ◽  
B. Ganesh Bhat ◽  
Jessica Woodring-Dietz ◽  
Suzhen Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulatory Element ◽  
Critical Role ◽  
Cell Types ◽  
Plasma Lipoproteins ◽  
Type I ◽  
Type Ii ◽  
Downstream Target ◽  
X Receptors

Abstract The liver X receptors (LXRs), members of the nuclear receptor superfamily, play an important role in controlling lipid homeostasis by activating several genes involved in reverse cholesterol transport. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apolipoprotein E, and cholesterol ester transport protein. They also play an important role in fatty acid metabolism by activating the sterol regulatory element-binding protein 1c gene. Here, we identify human LXRα (hLXRα) as an autoinducible gene. Induction in response to LXR ligands is observed in multiple human cell types including macrophages and occurs within 2–4 h. Analysis of the hLXRα promoter revealed three LXR response elements (LXREs); one exhibits strong affinity for both LXRα:RXR and LXRβ:RXR (a type I LXRE), and deletion and mutational studies indicate it plays a critical role in LXR-mediated induction. The other two LXREs are identical to each other, exist within highly conserved Alu repeats, and exhibit selective binding to LXRα:RXR (type II LXREs). In transfections, the type I LXRE acts as a strong mediator of both LXRα and LXRβ activity, whereas the type II LXRE acts as a weaker and selective mediator of LXRα activity. Our data suggest a model in which LXR ligands trigger an autoregulatory loop leading to selective induction of hLXRα gene expression. This would lead to increased hLXRα levels and transcription of its downstream target genes such as ABCA1, providing a simple yet exquisite mechanism for cells to respond to LXR ligands and cholesterol loading.

Physiology of Neuronal Subtypes in the Respiratory–Vocal Integration Nucleus Retroamigualis of the Male Zebra Finch

2005 ◽  
Vol 94 (4) ◽  
pp. 2379-2390 ◽  
Author(s):  
M. F. Kubke ◽  
Y. Yazaki-Sugiyama ◽  
R. Mooney ◽  
J. M. Wild
Keyword(s):  
Motor Neurons ◽  
Zebra Finch ◽  
Synaptic Input ◽  
Cell Types ◽  
Inhibitory Input ◽  
Type I ◽  
Type Ii ◽  
Intracellular Recordings ◽  
Electrophysiological Properties ◽  
Premotor Neurons

Learned vocalizations, such as bird song, require intricate coordination of vocal and respiratory muscles. Although the neural basis for this coordination remains poorly understood, it likely includes direct synaptic interactions between respiratory premotor neurons and vocal motor neurons. In birds, as in mammals, the medullary nucleus retroambigualis (RAm) receives synaptic input from higher level respiratory and vocal control centers and projects to a variety of targets. In birds, these include vocal motor neurons in the tracheosyringeal part of the hypoglossal motor nucleus (XIIts), other respiratory premotor neurons, and expiratory motor neurons in the spinal cord. Although various cell types in RAm are distinct in their anatomical projections, their electrophysiological properties remain unknown. Furthermore, although prior studies have shown that RAm provides both excitatory and inhibitory input onto XIIts motor neurons, the identity of the cells in RAm providing either of these inputs remains to be established. To characterize the different RAm neuron types electrophysiologically, we used intracellular recordings in a zebra finch brain stem slice preparation. Based on numerous differences in intrinsic electrophysiological properties and a principal components analysis, we identified two distinct RAm neuron types (types I and II). Antidromic stimulation methods and intracellular staining revealed that type II neurons, but not type I neurons, provide bilateral synaptic input to XIIts. Paired intracellular recordings in RAm and XIIts further indicated that type II neurons with a hyperpolarization-dependent bursting phenotype are a potential source of inhibitory input to XIIts motor neurons. These results indicate that electrically distinct cell types exist in RAm, affording physiological heterogeneity that may play an important role in respiratory–vocal signaling.

scholarly journals Making a connection: direct binding between keratin intermediate filaments and desmosomal proteins.

1994 ◽  
Vol 127 (4) ◽  
pp. 1049-1060 ◽  
Author(s):  
P D Kouklis ◽  
E Hutton ◽  
E Fuchs
Keyword(s):  
Intermediate Filaments ◽  
Transmembrane Domain ◽  
Direct Interaction ◽  
Cell Types ◽  
Epidermal Keratinocytes ◽  
Type I ◽  
Type Ii ◽  
Amino Terminal ◽  
Keratin Intermediate Filaments

In epidermal cells, keratin intermediate filaments connect with desmosomes to form extensive cadherin-mediated cytoskeletal architectures. Desmoplakin (DPI), a desmosomal component lacking a transmembrane domain, has been implicated in this interaction, although most studies have been conducted with cells that contain few or no desmosomes, and efforts to demonstrate direct interactions between desmoplakin and intermediate filaments have not been successful. In this report, we explore the biochemical nature of the connections between keratin filaments and desmosomes in epidermal keratinocytes. We show that the carboxy terminal "tail" of DPI associates directly with the amino terminal "head" of type II epidermal keratins, including K1, K2, K5, and K6. We have engineered and purified recombinant K5 head and DPI tail, and we demonstrate direct interaction in vitro by solution-binding assays and by ligand blot assays. This marked association is not seen with simple epithelial type II keratins, vimentin, or with type I keratins, providing a possible explanation for the greater stability of the epidermal keratin filament architecture over that of other cell types. We have identified an 18-amino acid residue stretch in the K5 head that is conserved only among type II epidermal keratins and that appears to play some role in DPI tail binding. This finding might have important implications for understanding a recent point mutation found within this binding site in a family with a blistering skin disorder.

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