Inorganic pyrophosphate generation and disposition in pathophysiology

2001 ◽  
Vol 281 (1) ◽  
pp. C1-C11 ◽  
Author(s):  
Robert A. Terkeltaub

Inorganic pyrophosphate (PPi) regulates certain intracellular functions and extracellular crystal deposition. PPiis produced, degraded, and transported by specialized mechanisms. Moreover, dysregulated cellular PPiproduction, degradation, and transport all have been associated with disease, and PPiappears to directly mediate specific disease manifestations. In addition, natural and synthetic analogs of PPiare in use or currently under evaluation as prophylactic agents or therapies for disease. This review summarizes recent developments in the understanding of how PPiis made and disposed of by cells and assesses the body of evidence for potentially significant physiological functions of intracellular PPiin higher organisms. Major topics addressed are recent lines of molecular evidence that directly link decreased and increased extracellular PPilevels with diseases in which connective tissue matrix calcification is disordered. To illustrate in depth the effects of disordered PPimetabolism, this review weighs the roles in matrix calcification of the transmembrane protein ANK, which regulates intracellular to extracellular movement of PPi, and the PPi-generating phosphodiesterase nucleotide pyrophosphatase family isoenzyme plasma cell membrane glycoprotein-1 (PC-1).

1938 ◽  
Vol 68 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Lester S. King

Trypan blue injected intravenously is bound almost at once by the intercellular connective tissue elements all over the body,—by collagen, reticulin, and elastic fibers. This union of dye and tissue elements is the factor responsible for the early macroscopic blue color and is antecedent to cellular colloidopexic action. Different examples of connective tissue differ among themselves in their ability to hold the dye. Diffuse staining of elastic fibers noted by previous observers is merely a special case of the general affinity of connective tissue for the dye. The evidence suggests that the histiocytes are cells specialized to segregate noxae that become diffusely bound to the intercellular connective tissue matrix.


2004 ◽  
Vol 286 (5) ◽  
pp. C1177-C1187 ◽  
Author(s):  
Sucheta M. Vaingankar ◽  
Thomas A. Fitzpatrick ◽  
Kristen Johnson ◽  
James W. Goding ◽  
Michele Maurice ◽  
...  

The ectonucleoside pyrophosphatase phosphodiesterase 1 (NPP1/PC-1) is a member of the NPP enzyme family that is critical in regulating mineralization. In certain mineralizing sites of bone and cartilage, membrane-limited vesicles [matrix vesicles (MVs)] provide a sheltered internal environment for nucleation of calcium-containing crystals, including hydroxyapatite. MV formation occurs by budding of vesicles from the plasma membrane of mineralizing cells. The MVs are enriched in proteins that promote mineralization. Paradoxically, NPP1, the type II transmembrane protein that generates the potent hydroxyapatite crystal growth inhibitor inorganic pyrophosphate (PPi), is also enriched in MVs. Although osteoblasts express NPP1, NPP2, and NPP3, only NPP1 is enriched in MVs. Therefore, this study uses mineralizing human osteoblastic SaOS-2 cells, a panel of NPP1 mutants, and NPP1 chimeras with NPP3, which does not concentrate in MVs, to investigate how NPP1 preferentially targets to MVs. We demonstrated that a cytosolic dileucine motif (amino acids 49–50) was critical in localizing NPP1 to regions of the plasma membrane that budded off into MVs. Moreover, transposition of the NPP1 cytoplasmic dileucine motif and flanking region (AAASLLAP) to NPP3 conferred to NPP3 the ability to target to the plasma membrane and, subsequently, concentrate in MVs. Functionally, the cytosolic tail dileucine motif NPP1 mutants lost the ability to support MV PPi concentrations and to suppress calcification. The results identify a specific targeting motif in the NPP1 cytosolic tail that delivers PPi-generating NPP activity to osteoblast MVs for control of calcification.


2020 ◽  
Vol 14 (2) ◽  
pp. 108-125
Author(s):  
Apoorva Singh ◽  
Nimisha

: Skin cancer, among the various kinds of cancers, is a type that emerges from skin due to the growth of abnormal cells. These cells are capable of spreading and invading the other parts of the body. The occurrence of non-melanoma and melanoma, which are the major types of skin cancers, has increased over the past decades. Exposure to ultraviolet radiations (UV) is the main associative cause of skin cancer. UV exposure can inactivate tumor suppressor genes while activating various oncogenes. The conventional techniques like surgical removal, chemotherapy and radiation therapy lack the potential for targeting cancer cells and harm the normal cells. However, the novel therapeutics show promising improvements in the effectiveness of treatment, survival rates and better quality of life for patients. Different methodologies are involved in the skin cancer therapeutics for delivering the active ingredients to the target sites. Nano carriers are very efficient as they have the ability to improve the stability of drugs and further enhance their penetration into the tumor cells. The recent developments and research in nanotechnology have entitled several targeting and therapeutic agents to be incorporated into nanoparticles for an enhancive treatment of skin cancer. To protect the research works in the field of nanolipoidal systems various patents have been introduced. Some of the patents acknowledge responsive liposomes for specific targeting, nanocarriers for the delivery or co-delivery of chemotherapeutics, nucleic acids as well as photosensitizers. Further recent patents on the novel delivery systems have also been included here.


2001 ◽  
Vol 124 (4) ◽  
pp. 459-463 ◽  
Author(s):  
David B. Wexler ◽  
Gilead Berger ◽  
Ari Derowe ◽  
Dov Ophir

OBJECTIVE: In this study we sought to define the histologic changes produced by laser treatment of inferior turbinates. STUDY DESIGN: Eight inferior turbinates with prior laser treatment (mean, 26.8 months) were analyzed by light microscopy after turbinectomy for relief of refractory nasal obstruction. Histologic findings were compared with those of a group of 8 hypertrophic inferior turbinates that had no previous laser surgery. RESULTS: Laser-treated areas of the inferior turbinates demonstrated a histologically bland appearance, with marked diminution of seromucinous glands and relative preponderance of connective tissue matrix. Prominence of venous sinusoids was also significantly reduced in the laser-treated areas. Surface epithelium including goblet cells was reconstituted over the areas of laser application. CONCLUSION: Clinical laser surgery of the inferior turbinate produces striking long-term histologic changes. SIGNIFICANCE: The data suggest a differential response of turbinate histologic components to application of laser energy, with the glandular component being particularly sensitive. Further correlative study is needed to clarify the clinical significance of laser-induced histologic changes in inferior turbinates.


Author(s):  
Tulio F. Villalobos-Guerrero ◽  
Taeseo Park ◽  
Izwandy Idris

Abstract The present study reviews Perinereis Group 2 species from the Eastern and South-eastern Asian seas based on morphological analysis of the types, non-types and original descriptions, and the use of molecular evidence (COI and 16S rDNA) from newly collected material. These species are characterized by having two bar-shaped paragnaths on pharyngeal area VI, which are often deemed conical when small and pointed, triggering misidentifications as to Neanthes species. New terminology and definition for this particular type of bars are proposed, and the generic position of some resembling Neanthes species is also re-assessed. Five species are transferred to Perinereis: Perinereis babuzai comb. nov., P. belawanensis comb. nov., P. kinmenensis comb. nov., P. shigungensis comb. nov. and P. vitabunda comb. nov. ‘Perinereis aibuhitensis’ species group is newly proposed by encompassing species having proximal dorsal ligule similar throughout the body, dorsal cirri short, and blades of heterogomph falcigers straight with long terminal tooth forming a distinct tendon. Perinereis belawanensis comb. nov., P. linea and P. vitabunda comb. nov. are redescribed. Perinereis linea is regarded as a senior synonym of Nereis (Neanthes) orientalis and Perinereis vancaurica tetradentata based on type material, whereas its exotic status in the Mediterranean Sea is questioned. An identification key to all currently valid species within Perinereis Group 2 is also provided.


1960 ◽  
Vol 8 (3) ◽  
pp. 719-760 ◽  
Author(s):  
Gabriel C. Godman ◽  
Keith R. Porter

The role of the cells in the fabrication of a connective tissue matrix, and the structural modifications which accompany cytodifferentiation have been investigated in developing epiphyseal cartilage of fetal rat by means of electron microscopy. Differentiation of the prechondral mesenchymal cells to chondroblasts is marked by the acquisition of an extensive endoplasmic reticulum, enlargement and concentration of the Golgi apparatus, the appearance of membrane-bounded cytoplasmic inclusions, and the formation of specialized foci of increased density in the cell cortex. These modifications are related to the secretion of the cartilage matrix. The matrix of young hyaline cartilage consists of groups of relatively short, straight, banded collagen fibrils of 10 to 20 mµ and a dense granular component embedded in an amorphous ground substance of moderate electron density. It is postulated that the first phase of fibrillogenesis takes place at the cell cortex in dense bands or striae within the ectoplasm subjacent to the cell membrane. These can be resolved into sheaves of "primary" fibrils of about 7 to 10 mµ. They are supposedly shed (by excortication) into the matrix space between the separating chondroblasts, where they may serve as "cores" of the definitive matrix fibrils. The diameter of the fibrils may subsequently increase up to threefold, presumably by incorporation of "soluble" or tropocollagen units from the ground substance. The chondroblast also discharges into the matrix the electrondense amorphous or granular contents of vesicles derived from the Golgi apparatus, and the mixed contents of large vacuoles or blebs bounded by distinctive double membranes. Small vesicles with amorphous homogeneous contents of moderate density are expelled in toto from the chondroblasts. In their subsequent evolution to chondrocytes, both nucleus and cytoplasm of the chondroblasts undergo striking condensation. Those moving toward the osteogenic plate accumulate increasingly large stores of glycogen. In the chondrocyte, the enlarged fused Golgi vesicles with dense contents, massed in the juxtanuclear zone, are the most prominent feature of the cytoplasm. Many of these make their way to the surface to discharge their contents. The hypertrophied chondrocytes of the epiphyseal plate ultimately yield up their entire contents to the matrix.


2018 ◽  
Author(s):  
◽  
Jennifer Torrence

What does the musician become when sound and instrumental thinking are no longer privileged as the foundation of a musician's practice? In what ways does an emphasis on the musician's body cause music to approach art forms such as theatre and performance? After a generation of pioneering work from Mauricio Kagel, Dieter Schnebel, John Cage and many others, where is the theatrical and the performative in music today? How do its recent developments shape, alter, constitute a musician's artistic practice? Through her research, Jennifer Torrence argues that this type of music demands the musician assume a different understanding and relation to their instrument and therefore a different relation to their body. This relation calls for new ways of making and doing (new artistic practices) that foreground the body as a fundamental performance material. Through an emphasis on the body, the musician emerges as a performer. This exposition is a reflection on the research project Percussion Theatre: a body in between. This project is comprised of a collection of new evening-length works that approach the theatrical and performative in contemporary music performance. These works are created with and by composers Wojtek Blecharz, Carolyn Chen, Neo Hülcker, Johan Jutterström, Trond Reinholdtsen, François Sarhan, and Peter Swendsen. The exposition contains reflections on recent developments in contemporary music that mark a mutation of the executing musician into a co-creating performer, as well as images, artefacts, videos, and texts that unfold the process of creating and performing the work that constitutes this project. The ambition of this exposition is that through the exposure of a personal artistic practice an image of a larger field may come into focus.


Author(s):  
Elisabeth El Refaie

This chapter critically reviews the traditional notion of embodiment in Conceptual Metaphor Theory (CMT), arguing that it is characterized by a somewhat inflexible view of the way the human body shapes one’s thinking. Probing more recent developments in CMT, including dynamic systems approaches and cross-cultural studies of metaphor, and confronting these with key theories from phenomenology, psychology, social semiotics, and media theory, the original notion of dynamic embodiment is developed. Accordingly, the degree to which people draw on their own bodies when producing and interpreting metaphors depends not only on the cultural practices and the specific actions in which they are engaged at any given moment, but also on the degree to which they are consciously aware of their physicality, as well as the affordances of the modes and media they are using to communicate.


Sign in / Sign up

Export Citation Format

Share Document