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PGP
Terms modified by PGP Selected AbstractsMorphology and histology of the larynx of the common toad Rhinella arenarum (Hensel, 1867) (Anura, Bufonidae)ACTA ZOOLOGICA, Issue 4 2009Gladys N. Hermida Abstract The structure of the larynx of the toad Rhinella arenarum was exhaustively studied. The laryngeal skeleton consists of three bilaterally symmetrical cartilages: the cricoid and two arytenoids. Internally, each half-larynx has an anterior and a posterior chamber. The first chamber is delimited by the epithelium covering the arytenoid cartilage and the anterior membrane. The latter consists of fibro-elastic tissue and contains blood capillaries that, judging by their location and distribution, might serve to maintain vocal cord turgidity. At the level of the cricoid cartilage, two structures are reported here for the first time: the posterodorsal and the anteroventral processes. Both processes are associated with the insertion of the posterior membrane. A cartilaginous rod is located at the free margin of the posterior membrane. This rod appears to support the membrane when the air flows. The distal portion of the larynx communicates with the proximal region of the lung. The epithelium of the laryngeal mucosa contains ciliated cells, goblet cells, secretory cells with short microvilli and neuroendocrine cells immunopositive to PGP 9.5. The results obtained in this study provide new information about the internal organization of the larynx in anurans, which could serve as additional morphological characters for phylogenetic relationships. [source] Expression of the Multidrug Transporter P-glycoprotein in Brain Capillary Endothelial Cells and Brain Parenchyma of Amygdala-kindled RatsEPILEPSIA, Issue 7 2002Ulrike Seegers Summary: ,Purpose: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P-glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala-kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs. Methods: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode-implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti-PGP antibody. Six brain regions were examined ipsi- and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum. Results: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate-treated rats were used as positive controls. As reported previously, kainate-induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions. Conclusions: Amygdala-kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance,associated protein, might be involved in the resistance of kindled rats to AEDs. [source] Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjectsHISTOPATHOLOGY, Issue 5 2007E P Wilder-Smith Aims:, The transient receptor potential vanilloid 1 (TRPV1) plays an important role in mediating pain and heat. In painful neuropathies, intraepidermal TRPV1 nerve fibre expression is low or absent, suggesting that pain generated is not directly related to sensory nerve fibres. Recent evidence suggests that keratinocytes may act as thermal receptors via TRPV1. The aim was to investigate epidermal TRPV1 expression in patients with neuropathic conditions associated with pain. Methods and results:, In a prospective study of distal small nerve fibre neuropathy (DISN; n = 13) and diabetic neuropathy (DN; n = 12) intraepidermal nerve fibre density was assessed using the pan axonal marker PGP 9.5 and epidermal TPVR1 immunoreactivity compared with controls (n = 9). Intraepidermal nerve fibres failed to show TRPV1 immunoreactivity across all groups. There was moderate and strong TRPV1 reactivity of epidermal keratinocytes in 41.8% and 6% for DISN, 32.9% and 2.9% for DN and 25.4% and 5.1% for controls, respectively. Moderate keratinocyte TRPV1 expression was significantly increased in DISN compared with controls (P = 0.01). Conclusion:, Our study suggests that in human painful neuropathies, epidermal TRPV1 expression is mainly in keratinocytes. [source] The percentage of gutta-percha-filled area in simulated curved canals when filled using Endo Twinn, a new heat device sourceINTERNATIONAL ENDODONTIC JOURNAL, Issue 8 2006G. Pagavino Abstract Aim, To compare the percentage of gutta-percha-filled area (PGP) in simulated root canals when varying the penetration depth and function of the pluggers (heat versus heat plus vibration) using Endo Twinn. Methodology, Sixty-four resin blocks with simulated 34,35° curved canals were randomly divided into two groups in order to obtain two canal shapes: group A with 0.8 taper and group B with 0.4 taper. The apical portion of each canal was prepared to a size 20 K-file. The canals were filled with gutta-percha in combination with a root canal sealer. In each group 16 canals were filled using the Endo Twinn heat function and 16 canals by means of both the heat and the vibration function. All samples were sectioned horizontally at three levels (1.25, 2.5 and 4.0 mm from the working length) and the PGP was measured. Data were analysed using anova test. Results, At the 1.25 mm level PGP was significantly greater using the vibration function (P = 0.0329) and in 0.8 taper canals (P < 0.0001). At the 2.5 mm level the PGP was greater in the canals with 0.8 taper compared with a 0.4 taper with or without vibration (vibration, P = 0.0056; interaction taper-vibration, P = 0.0020). In 0.4 taper canals the PGP was greater when the vibration function was activated. At the 4 mm level in 0.8 taper canals there was no significant difference in PGP with or without the vibration (P = 0.6742). Conclusions, 0.8 taper canals had significantly greater PGP than 0.4 taper canals. At the 1.25 mm level there was significantly greater PGP when the vibration function was activated. [source] Implementation of a stabilized finite element formulation for the incompressible Navier,Stokes equations based on a pressure gradient projectionINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 4 2001Ramon Codina Abstract We discuss in this paper some implementation aspects of a finite element formulation for the incompressible Navier,Stokes equations which allows the use of equal order velocity,pressure interpolations. The method consists in introducing the projection of the pressure gradient and adding the difference between the pressure Laplacian and the divergence of this new field to the incompressibility equation, both multiplied by suitable algorithmic parameters. The main purpose of this paper is to discuss how to deal with the new variable in the implementation of the algorithm. Obviously, it could be treated as one extra unknown, either explicitly or as a condensed variable. However, we take for granted that the only way for the algorithm to be efficient is to uncouple it from the velocity,pressure calculation in one way or another. Here we discuss some iterative schemes to perform this uncoupling of the pressure gradient projection (PGP) from the calculation of the velocity and the pressure, both for the stationary and the transient Navier,Stokes equations. In the first case, the strategies analyzed refer to the interaction of the linearization loop and the iterative segregation of the PGP, whereas in the second the main dilemma concerns the explicit or implicit treatment of the PGP. Copyright © 2001 John Wiley & Sons, Ltd. [source] Cutaneous melanocytoneuroma: the first case of a distinctive intraneural tumor with dual nerve sheath and melanocytic differentiationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2007Ilan Weinreb Many melanocytic nevi contain areas similar to nerve sheath tumors (NST) and NSTs with melanin have been described. There are some NSTs with at least partial intraneural location, including neurofibromas, plexiform neurofibromas, granular cell tumors and the recently described, dendritic cell neurofibroma with pseudorosettes. We describe the case of an NST with melanocytic differentiation and intraneural location, for which we suggest the term ,melanocytoneuroma' (MCN). It arose in the skin of a 67-year-old woman with no previous history of melanoma or neurofibromatosis. The lesion presented as a papule and histologically consisted of a dermal nodule without junctional melanocytic activity. The lesion comprised an intraneural proliferation of large epithelioid eosinophilic cells with prominent cell borders imparting a ,plant-like' appearance. The cells were also seen within adjacent nerve twigs and were positive for S100, Melan-A, HMB-45, microphthalmia transcription factor and PGP 9.5. The lesion was entirely surrounded by an epithelial membrane antigen-positive-perineurial coat and the individual tumor cells were invested by laminin and collagen type-IV-positive basal lamina-like material. The lesion did not show any evidence of atypia and following complete excision, no recurrence has been documented. In conclusion, this unusual lesion represents an intraneural proliferation with melanocytic and nerve sheath cell differentiation, to which we have accorded the appellation, MCN. [source] Expression of PGP 9.5 in granular cell nerve sheath tumors: an immunohistochemical study of six casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2001Meera Mahalingam Background: Protein gene product 9.5 (PGP 9.5) is expressed in brain at 20 to 50 times the levels detected in other organs. Immunohistochemical studies reveal this protein is localized to both central and peripheral neurons. Recently, PGP 9.5 is reported to be a useful marker for cellular neurothekeomas. Herein we test whether PGP 9.5 is a new marker for granular cell nerve sheath tumors. Material and Methods: An immunohistochemical analysis for PGP 9.5 expression was carried out on all cases with the diagnosis of granular cell nerve sheath tumor seen over a 2-year period. In addition, we compared expression of PGP 9.5 with other accepted markers for neuroectodermal tumors including anti-S-100 protein and NKI/C3 monoclonal antibodies. Results: Six granular cell nerve sheath tumors were diagnosed in over 80,000 dermatopathology specimens in the two-year period. These cases were all positive for PGP 9.5 as well as for S-100 protein and NK1/C3. Conclusion: These findings identify PGP 9.5 as a new immunohistochemical marker for use in the diagnosis of granular cell tumors. They also strengthen the histogenetic relationship between granular cell nerve sheath tumors and tumors of Schwann cell or perineurial origin. [source] Petunia Germinating Pollen S/D3 Interacts with S-RNases in Petunia hybrida Vilm.JOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 5 2006Yan-Xia Guo Abstract Self-incompatibility (SI) is a genetic mechanism of self/non-self pollen recognition to prevent self-fertilization in many flowering plants and, in most cases, this is controlled by a multi-allelic S-locus. S-RNase and S-locus F box (SLF) proteins have been shown to be the female and male determinants of gametophytic self-incompatibility (GSI), respectively, in the Solanaceae, Scrophulariaceae and Rosaceae. Nevertheless, it is thought that additional factors are required for the SI response. Herein, we constructed a mature anther cDNA library from a self-incompatible Petunia hybrida Vilm. line of the S3S3 haplotype. Using AhS2-RNase from Antirrhinum hispanicum as a bait for yeast two-hybrid screening, we found that petunia germinating pollen (PGP) S/D3 was capable of interacting physically with the bait. However, the interaction lacked haplotype specificity. The PGPS/D3 gene is a single copy gene that is expressed in tissues such as the style, ovary, pollen, and leaf. The PGPS/D3::GFP (green fluorescence protein) construct was detected in both the membrane and cytoplasm. The implications of these findings in the operation of S-RNase-based SI are discussed. (Managing editor: Li-Hui Zhao) [source] High throughput synthesis and screening of new protein resistant surfaces for membrane filtrationAICHE JOURNAL, Issue 7 2010Mingyan Zhou Abstract A novel high throughput method for synthesis and screening of customized protein-resistant surfaces was developed. This method is an inexpensive, fast, reproducible and scalable approach to synthesize and screen protein-resistance surfaces appropriate for a specific feed. The method is illustrated here by combining a high throughput platform (HTP) approach together with our patented photo-induced graft polymerization (PGP) method developed for facile modification of commercial poly(aryl sulfone) membranes. This new HTP-PGP method was validated by comparison with our previous published results obtained using a bench-scale filtration assay of six well-studied monomers. Optimally-performing surfaces for resisting a model protein, bovine serum albumin (BSA), were identified from a library of 66 monomers. Surfaces were prepared via graft polymerization onto poly(ether sulfone) (PES) membranes and were evaluated using a protein adsorption assay followed by pressure-driven filtration. Bench-scale verification was conducted for selected monomers using HTP-PGP method; a good correlation with HTP-PGP results was found. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Disorder-specific changes in innervation in oral lichen planus and lichenoid reactionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2000Sirkku Niissalo Abstract: The peripheral nervous system was analysed in the oral mucosa of eight patients with oral lichen planus (OLP), five with a lichenoid reaction (LR) and three with mild chronic inflammation (MCI), by morphometric analysis of nerve fibres containing immunoreactive PGP 9.5, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), or C-flanking peptide of neuropeptide Y (CPON). Overall nerve fibre density was higher in OLP (P=0.039) and LR (P=0.026) compared with healthy oral mucosa and was compatible with sprouting and collateral formation. In contrast to the innervation visualized with structural nerve fibre-marker PGP 9.5, the densities of neuropeptide-immunoreactive nerves were low in inflamed tissue. This is consistent with depletion via local release. Retraction and local loss of innervation were found in areas coinciding with the most severe inflammation and basal membrane (BM) damage. Interestingly, LR showed a twenty-eight-fold loss of post-ganglionic CPON-ir sympathetic nerve fibres (P=0.044). In LR, CPON-ir innervation was markedly lower than in OLP. Finally, the pattern of innervation in relation to inflammatory cell infiltrates and tissue structures differed between OLP and LR. In conclusion, the peripheral nervous system is implicated in the immunopathogenesis of lichen planus and lichenoid reactions, with a disorder-specific difference in this involvement. [source] Neurokinin 1-receptors and sensory neuropeptides in tendon insertions at the medial and lateral epicondyles of the humerus Studies on tennis elbow and medial epicondylalgiaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2004Björn-Ove Ljung Abstract There is no information on the sensory innervation at the flexor muscle origin at the medial epicondyle of the humerus and it is not known if substance P receptors (Neurokinin 1-receptors, NK1-R) are present in tendon insertions in general. In the present investigation, we have studied the muscle origin in patients suffering from medial epicondylalgia and tennis elbow. Immunohistochemistry and antibodies to substance P (SP) and CGRP as well as the general nerve marker PGP 9.5 were used. Specific immunoreactions were observed in nerve bundles and as free nerve fibers. The immunoreactive structures were partly seen in association with some of the blood vessels. The observations constitute a morphological correlate for the occurrence of nerve mediated effects in this region. By using immunohistochemistry and antibodies to NK1-R, the distribution of this receptor was studied at the insertion of the proximal tendon of the extensor carpi radialis brevis muscle at the lateral epicondyle. Specific immunoreactions were seen as varicose fibers occurring as single fibers or grouped into bundles, indicating that SP has effects in the nerves in this region. The results give further evidence for a possible neurogenic involvement in the pathophysiology of tennis elbow and in medial epicondylalgia. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Cytokines alter the expression and activity of the multidrug resistance transporters in human hepatoma cell lines; analysis using RT-PCR and cDNA microarraysJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2003Gigi Lee Abstract Pro-inflammatory cytokines suppress the hepatic expression of the multidrug resistance transporters in rodents, indicating potential usefulness in chemotherapy. Our objective was to investigate their impact in human hepatoma cells. HuH 7 and HepG2 cells were treated with IL-1,, IL-6, or TNF-, for 0,72 h. Expression and activity of MDR1 and the MRP (MRP1, 2, 3, and 6) transporters were examined by RT-PCR, efflux assays, and microarrays. Significant reductions in the MDR1-mediated efflux of Rhodamine 123 and MDR1 mRNA levels were observed in HuH 7 cells treated with IL-6, TNF-,, or IL-1, and in TNF-,,treated HepG2 cells. However, cytokine-treated HuH7 cells also demonstrated 1.6- to 2.6-fold greater efflux of the MRP substrate, 5-carboxyfluorescein (5-CF) and higher MRP3 mRNA levels (p,<,0.05). IL-1, and IL-6 treatments increased MRP activity and MRP1 mRNA levels in HepG2 cells (p,<,0.05). Microarrays studies performed in IL-6 and TNF-,,treated HepG2 cells detected similar changes in the expression of the MDR1 and MRP transporters, but this did not reach significance. However, the microarrays confirmed cytokine-mediated induction of several acute phase proteins. Our data suggests that although cytokine-mediated suppression of PGP may alter drug resistance in malignant cells, these cytokines may also impose an induction in other multidrug resistance genes. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2152,2163, 2003 [source] Immunohistochemical and electron microscopic study of extrinsic hepatic reinnervation following orthotopic liver transplantation in ratsLIVER INTERNATIONAL, Issue 5 2001Tsuyoshi Takahashi Abstract:Background/Aims: Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. Methods: Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). Results: Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. Conclusion: The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats. [source] Long-term morphometric and immunohistochemical findings in human free microvascular muscle flaps,MICROSURGERY, Issue 1 2004M. Susanna C. Kauhanen M.D., Ph.D. Reinnervation, muscle regeneration, density of microvessels, and muscle-type specific atrophy were studied 3,4 years after surgery in surgically nonreinnervated free microvascular muscle flaps to 13 patients transplanted to the upper or lower extremities. Routine histology and immunohistochemistry for PGP 9.5 and S-100 (neuronal markers), Ki-67 (cell proliferation), myosin (muscle fiber types), and CD-31 (endothelium) were carried out, and results were analyzed morphometrically. Three to 4 years after surgery, severe atrophy of predominantly slow-type fibers was seen in 9 cases. In 4 cases, muscle-fiber diameter and fiber-type distribution were close to normal. Long intraoperative muscle ischemia and postoperative immobilization were associated with poor muscle bulk in flaps. The density of microvessels in flaps did not differ from control muscles. PGP 9.5 and S-100 immunopositive nerve fibers were detected in 7 patients. Reinnervation was associated with good muscle bulk. In 4 patients, activation of satellite cells was evident. The results suggest that in some cases, spontaneous reinnervation may occur in free muscle flaps, and that several years after microvascular free flap transfer, the muscle still attempts to regenerate. © 2004 Wiley-Liss, Inc. [source] Expression pattern of acetylated ,-tubulin in porcine spermatogoniaMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2010Jinping Luo Mammalian spermatogonial stem cells reside on the basement membrane of the seminiferous tubules. The mechanisms responsible for maintenance of spermatogonia at the basement membrane are unclear. Since acetylated ,-tubulin (Ac-,-Tu) is a component of long-lived, stable microtubules and deacetylation of ,-tubulin enhances cell motility, we hypothesized that acetylation of ,-tubulin might be associated with positioning of spermatogonia at the basement membrane. The expression pattern of Ac-,-Tu at different stages of testis development was characterized by immunohistochemistry for Ac-,-Tu and spermatogonia-specific proteins (PGP 9.5, DAZL). In immature pig testes, Ac-,-Tu was present exclusively in gonocytes at 1 week of age, and in a subset of spermatogonia at 10 weeks of age. At this age, spermatogonia are migrating toward the tubule periphery and Ac-,-Tu appeared polarized toward the basement membrane. In adult pig testes, Ac-,-Tu was detected in few single or paired spermatogonia at the basement membrane as well as in spermatids and spermatozoa. Only undifferentiated (DAZL,), proliferating (determined by BrdU incorporation) spermatogonia expressed high levels of Ac-,-Tu. Comparison with the expression pattern of ,-tubulin and tyrosinated ,-tubulin confirmed that only Ac-,-Tu is specific to germ cells. The unique pattern of Ac-,-Tu in undifferentiated germ cells during postnatal development suggests that posttranslational modifications of microtubules may play an important role in recruiting and anchoring spermatogonia at the basement membrane. Mol. Reprod. Dev. 77: 348,352, 2010. © 2009 Wiley-Liss, Inc. [source] Nestin expression as a new marker in malignant peripheral nerve sheath tumorsPATHOLOGY INTERNATIONAL, Issue 2 2007Satoko Shimada Malignant peripheral nerve sheath tumor (MPNST) can be difficult to diagnose because it lacks specific immunohistochemical markers. S-100, which is a useful marker of MPNST, has limited diagnostic utility. Recent studies suggest that nestin, which is an intermediate filament protein, is expressed in neuroectodermal stem cells. The diagnostic utility of immunostains for nestin and three other neural markers (S-100, CD56 and protein gene product 9.5 (PGP 9.5)) were evaluated in 35 cases of MPNST and in other spindle cell tumors. All MPNST cases were strongly positive for nestin and had cytoplasmic staining. Stains for S-100, CD56, and PGP 9.5 were positive in fewer cases (17/35, 11/35, and 29/35 cases, respectively), and had less extensive staining. Nestin was negative in 10/10 leiomyomas, and weak nestin expression was seen in 10/10 schwannomas, 3/10 neurofibromas, 2/8 synovial sarcomas, 2/10 liposarcomas, 4/7 carcinosarcomas and 3/7 malignant fibrous histiocytomas. In contrast, strong nestin positivity was seen in 10/10 rhabdomyosarcomas, 15/19 leiomyosarcomas, and 9/9 desmoplastic melanomas. Nestin is more sensitive for MPNST than other neural markers and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST. [source] Dynamic mechanical analysis of pineapple leaf/glass hybrid fiber reinforced polyester compositesPOLYMER COMPOSITES, Issue 6 2010L. Uma Devi The dynamic mechanical properties of randomly oriented intimately mixed hybrid composites based on pineapple leaf fibers (PALF) and glass fibers (GF) in unsaturated polyester (PER) matrix were investigated. The PALFs have high-specific strength and improve the mechanical properties of the PER matrix. In this study, the volume ratio of the two fibers was varied by incorporating small amounts of GF such as PALF/GF, 90/10, 80/20, 70/30, and 50/50, keeping the total fiber loading constant at 40 wt%. The dynamic modulus of the compositeswas found to increase on GF addition. The intimately mixed (IM) hybrid composites with PALF/GF, 80/20 (0.2 Vf GF) showed highest E, values and least damping. Interestingly, the impact strength of the composites was minimum at this volume ratio. The composites with 0.46 Vf GF or PALF/GF (50/50) showed maximum damping behavior and highest impact strength. The results were compared with hybrid composites of different layering patterns such as GPG (GF skin and PALF core) and PGP (PALF skin and GF core). IM and GPG hybrid composites are found more effective than PGP. The activation energy values for the relaxation processes in different composites were calculated. The overall results showed that hybridization with GF enhanced the performance properties. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers [source] In vitro and in vivo degradation study on novel blends composed of polyphosphazene and polyester or polyanhydridePOLYMER INTERNATIONAL, Issue 6 2002Y Qiu Abstract Poly[bis(glycine ethyl ester)phosphazene] (PGP) was blended with poly(D,L -lactide- co -glycolide) (80:20 by mole) (PLGA) and poly[sebacic anhydride- co -trimellitylimidoglycine)- block -poly(ethylene glycol)] (30:50:20 by mole) (PSTP) in various ratios using a solvent-mixing technique. The in vitro degradation of polymer blends was examined by treatment in distilled water with or without lipase at 37,°C; the degradation rate of the blends could be regulated by adjusting the composition. PGP/PLGA (70:30 by wt) slabs took 120 days to disappear completely, while PGP/PSTP (70:30 by wt) needed only 20 days. Furthermore, Rhizopus delemer lipase showed the strongest acceleration activity on PGP/PLGA blends. The degree of enzymatic degradation was proportional to the percentage of PLGA in the blend. For comparison, the in vivo degradation of polymer blends was investigated by implanting them subcutaneously in the back of mice, some difference in degradation being observed. © 2002 Society of Chemical Industry [source] New Insights into the Neuromuscular Anatomy of the Ileocecal ValveTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2009Tamas Cserni Abstract The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better understanding of this important functional component of the gastrointestinal tract would enable surgeons to reconstruct an effective valve following surgical resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E) staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d) histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit immunohistochemistry were performed. The H+E staining revealed that the ICV consists of three muscle layers: an external circular muscle layer continuous with that of the ileal circular muscle layer, an inner circular muscle layer continuous with that of the cecal circular muscle layer, and a single longitudinal muscle layer, which appears to be secondary to a fusion of the ileal and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining revealed two distinct coaxial myenteric plexuses, together with superficial and deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric ICC network within the ICV. The structure of the neuromuscular components within the ICV suggests that the valve is a result of a simple intussusception of the terminal ileum into the cecum. This knowledge may help surgeons in their future attempts at reconstructing more anatomically and functionally suitable ICVs following surgical resection of native ICVs. Anat Rec 2009. © 2008 Wiley-Liss, Inc. [source] Increased Nerve Fiber Expression of Sensory Sodium Channels Nav1.7, Nav1.8, and Nav1.9 in Rhinitis,,THE LARYNGOSCOPE, Issue 4 2008Siew M. Keh MRCS Abstract Introduction: Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis. Materials and Methods: Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed. Results: All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P = .0004; Nav1.8, P = .028; Nav1.9, P = .02) and nonallergic (Nav1.7, P = .006; Nav1.8, P = .019; Nav1.9, P = .0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P = .01) and epithelial NGF immunoreactivity (P = .03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P = .06; macrophages, P = .044; T cells, P = .007) but not nonallergic rhinitis. Conclusion: The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis. [source] Combined Therapy with Atorvastatin and Calcineurin Inhibitors: No Interactions with TacrolimusAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2005W. P. D. Lemahieu Increased systemic exposure to statins and consequent risk for complications has been reported in patients concomitantly treated with cyclosporin A (CsA). This has been ascribed to inhibition of drug catabolism by cytochrome P450 3A4 (CYP3A4) or drug transport by P-glycoprotein (PGP) and organic anion transporting polypeptide (OATP1B1). It is not known whether the combination of statins and tacrolimus (Tac) also suffers from this drawback. Therefore, a pharmacokinetic study of atorvastatin and its metabolites was performed in 13 healthy volunteers after 4 days' treatment, and after short (12 h) concomitant exposure to CsA and Tac. A complementary assessment of overall CYP, and hepatic and intestinal CYP3A4 + PGP activity was performed after each treatment episode and compared to baseline (no drugs). Systemic exposure to atorvastatin acid and its metabolites was significantly increased when administered with CsA. In contrast, intake of Tac did not have any impact on atorvastatin pharmacokinetics. Concomitantly, a profound decrease of hepatic and intestinal PGP and an increase of intestinal CYP3A4 were noted with CsA, whereas no effect was seen after atorvastatin therapy with or without Tac. Based on these findings treatment with Tac appears a safer option for patients needing a combination of statins and calcineurin inhibitors. [source] Small nerve fiber involvement in systemic lupus erythematosus: A controlled studyARTHRITIS & RHEUMATISM, Issue 5 2002Roald Omdal Objective To determine if patients with systemic lupus erythematosus (SLE) may have a peripheral neuropathy involving unmyelinated and small, myelinated nerve fibers, by immunostaining epidermal nerve fibers (ENF) in skin biopsy samples for the panaxonal marker, protein gene product 9.5 (PGP 9.5). Methods Fifteen consecutive and nonselected SLE patients and 15 age- and sex-matched controls were included in the study. The age of the patients ranged from 25 years to 65 years, with a mean ± SD age of 47.3 ± 10.2 years and a disease duration of 2,28 years (mean ± SD 14.8 ± 8.6 years). Two 3-mm skin biopsy samples were obtained with a punch needle ,10 cm superior to the lateral malleolus of the right leg and immunostained with 0.1% rabbit polyclonal antibodies to human PGP 9.5. The number of ENF per millimeter was counted and recorded as the mean ± SD of counts in six 50-,m sections, 3 from each of the 2 biopsy samples. Results The mean number of ENF per mm in patients with SLE was 8.0 ± 1.5 (range 5.0,9.9), while the matched controls had 12.2 ± 3.8 ENF per mm (range 6.8,18.6) (P = 0.0006). Conclusion This study indicates that a small fiber involvement in patients with SLE may be responsible for the prevalent neuropathic symptoms and impaired warm sense that is observed in such patients. [source] Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosusBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008B. Maddison Summary Background, Lichen amyloidosus is a localized, chronic, pruritic skin disease characterized by deposition of amyloid in the papillary dermis. The pathogenesis of the pruritus of lichen amyloidosus is largely unknown. Objectives, To determine any change in the nerve fibre density in lichen amyloidosus lesions as an explanation for itch. Methods, Using an antibody to protein gene product (PGP) 9.5, the immunohistochemical analysis of the skin biopsies of 30 Hispanic patients with clinicopathologically proven lichen amyloidosus and of 11 healthy Hispanic controls matched for age, sex and site was performed. Results, Unexpectedly, the mean amount of PGP9.5 stain, a measure for nerve fibre amount, for the healthy controls was higher than the lichen amyloidosus group both in the epidermis (P < 0·0019) and dermoepidermal junction (P < 0·0064). No change was observed in the papillary dermis. Furthermore, the proportion of area covered by PGP9.5 showed a significant decrease in the epidermis (P < 0·0024) and dermoepidermal junction (P < 0·0075) in lichen amyloidosus compared with healthy controls. Age, gender and body site were found not to be influencing factors in nerve fibre amounts in lichen amyloidosus samples. Conclusions, We speculate that the severe pruritus observed in lichen amyloidosus might be the result of the hypersensitivity of the remaining nerve fibres as a response to an unexplained neurodegeneration of the absent nerve fibres. [source] P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Maria Ilaria Del Principe Summary. Concurrent resistance mechanisms, such as P-glycoprotein (PGP) and bcl-2, may contribute to a worse outcome in adult acute lymphoblastic leukaemia (ALL). Between 1990 and 2000, we analysed PGP and bcl-2 by flow cytometry, using two anti-PGP (C219 and JSB-1) monoclonal antibodies (mAbs) and an anti-bcl-2 mAb in 115 de novo adult ALL patients. Both a longer overall survival (OS) and longer disease-free survival (DFS) were observed in PGP-negative patients (23%vs 0% at 3 years, P = 0·011 and 29%vs 0% at 2 years, P = 0·006 for C219 respectively; 42%vs 0% at 1·5 years, P = 0·004 and 53%vs 0% at 8·5 months, P = 0·00006 for JSB-1 respectively). Bcl-2 positivity was associated with a significantly higher complete remission rate (90%vs 66%, P = 0·01). Moreover, in 69 patients not presenting with either t(9;22) or B-mature immunophenotype, PGP negativity (JSB-1) maintained its significant favourable prognostic impact with regard to OS (41%vs 0% at 1·5 years, P = 0·009) and DFS (83%vs 0% at 6 months, P = 0·0005). Importantly, within a subset of 62 patients with normal (n = 31) or unknown (n = 31) karyotype, PGP (JSB-1)-negative patients showed both a significantly longer OS and DFS (63%vs 0% at 1·4 years, P = 0·018 and 84%vs 0% at 6 months, P = 0·001 respectively). In multivariate analysis, JSB-1 (P = 0·008) and cytogenetics (P = 0·02) were found to be independent prognostic factors with regard to DFS. Therefore, in adult ALL, PGP and bcl-2 represent sensitive indicators of clinical outcome, and potential targets of novel molecules aimed at overcoming chemoresistance and recurrent relapses. [source] Determination of metastasis-associated proteins in non-small cell lung cancer by comparative proteomic analysisCANCER SCIENCE, Issue 8 2007Tian Tian The development of metastasis is the leading cause of death and an enormous therapeutic challenge in cases of non-small cell lung cancer. To better understand the molecular mechanisms underlying the metastasis process and to discover novel potential clinical markers for non-small cell lung cancer, comparative proteomic analysis of two non-small cell lung cancer cell lines with different metastatic potentials, the non-metastatic CL1-0 and highly metastatic CL1-5 cell lines, was carried out using two-dimensional electrophoresis followed by matrix-assisted laser desorption ionization,time of flight mass spectrometry and tandem mass spectrometry. Thirty-three differentially expressed proteins were identified unambiguously, among which 16 proteins were significantly upregulated and 17 proteins were downregulated in highly metastatic CL1-5 cells compared with non-metastatic CL1-0 cells. Subsequently, 8 of 33 identified proteins were selected for further validation at the mRNA level using real-time quantitative polymerase chain reaction, and three identified proteins, S100A11, PGP 9.5 and HSP27, were confirmed by western blotting. The protein S100A11 displaying significant differential expression at both the protein and mRNA levels was further analyzed by immunohistochemical staining in 65 primary non-small cell lung cancer tissues and 10 matched local positive lymph node specimens to explore its relationship with metastasis. The results indicated that the upregulation of S100A11 expression in non-small cell lung cancer tissues was significantly associated with higher tumor,node,metastasis stage (P = 0.001) and positive lymph node status (P = 0.011), implying that S100A11 might be an important regulatory molecule in promoting invasion and metastasis of non-small cell lung cancer. (Cancer Sci 2007; 98: 1265,1274) [source] In vitro and in vivo degradation study on novel blends composed of polyphosphazene and polyester or polyanhydridePOLYMER INTERNATIONAL, Issue 6 2002Y Qiu Abstract Poly[bis(glycine ethyl ester)phosphazene] (PGP) was blended with poly(D,L -lactide- co -glycolide) (80:20 by mole) (PLGA) and poly[sebacic anhydride- co -trimellitylimidoglycine)- block -poly(ethylene glycol)] (30:50:20 by mole) (PSTP) in various ratios using a solvent-mixing technique. The in vitro degradation of polymer blends was examined by treatment in distilled water with or without lipase at 37,°C; the degradation rate of the blends could be regulated by adjusting the composition. PGP/PLGA (70:30 by wt) slabs took 120 days to disappear completely, while PGP/PSTP (70:30 by wt) needed only 20 days. Furthermore, Rhizopus delemer lipase showed the strongest acceleration activity on PGP/PLGA blends. The degree of enzymatic degradation was proportional to the percentage of PLGA in the blend. For comparison, the in vivo degradation of polymer blends was investigated by implanting them subcutaneously in the back of mice, some difference in degradation being observed. © 2002 Society of Chemical Industry [source] On the efficiency of PGPS-based packet and cell switching technologies for traffic with guaranteed delayEUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 4 2003Fulvio Risso Circuit switching, suited to providing real-time services due to the low and fixed switching delay, is not cost effective for building integrated services networks because it is based on static allocation of resources which is not efficient with bursty data traffic. Moreover it cannot handle flows that are not integer multiple of 64,Kb/s, preventing the usage of low bit rate codecs. This work explores the most suitable alternatives to the circuit switching technology (i.e. packet/cell switching) from the efficiency point of view, assuming that a PGPS scheduler is deployed in the network nodes. The paper defines an index to measure the efficiency of packet telephony, i.e. the volume of real-time traffic with deterministically guaranteed quality plus the amount of data carried related to the amount of network resources used. Furthermore it determines the maximum efficiency obtainable by packet networks, compares different network technologies and explores the problems of the deploying of low bit-rate codecs. Copyright © 2003 AEI. [source] Intrinsic chemotherapy resistance to the tubulin-binding antimitotic agents in renal cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Roisean E. Ferguson Abstract Renal cancer is one of the most chemoresistant tumor types. Using a panel of 10 established renal cancer cell lines that have not been subjected to prior drug selection, the range of functional resistance phenotypes to the tubulin-binding agents paclitaxel, vinblastine, vincristine and patupilone (epothilone B, EPO906) was determined, together with expression of P-glycoprotein (PgP), multidrug resistance associated protein-2 (MRP2) and major vault protein (MVP) proteins. The IC50 values for vincristine correlated positively with PgP expression (r = 0.73; p = 0.031), with values for paclitaxel and vinblastine just failing to reach significance. A significant positive correlation was observed for sensitivity to paclitaxel and MRP2 expression only (r = 0.8; p = 0.013). MVP expression did not correlate with sensitivity to any of the drugs examined. All cell lines exhibited much greater sensitivity to patupilone, demonstrating for the first time the potential use of patupilone in this cancer. In tissue samples from chemotherapy-naive renal cell carcinoma (RCC) patients, marked downregulation or absence of PgP in many tumor cells with expression levels more similar to sensitive cell lines rather than the resistant lines was seen. Similarly, MRP2 was absent or only weakly present in tumor cells, whereas MVP was very strongly upregulated in most tumor samples. This study illustrating discrepancies between results exclusively based on studies in cell lines and findings in vivo suggests that the role of PgP and MRP2 in intrinsic resistance in RCC in vivo may be less than expected from the in vitro findings and supports a potential role for MVP on the basis of in vivo expression studies. © 2004 Wiley-Liss, Inc. [source] Upregulation of Brain Expression of P-Glycoprotein in MRP2-deficient TR - Rats Resembles Seizure-induced Up-regulation of This Drug Efflux Transporter in Normal RatsEPILEPSIA, Issue 4 2007Katrin Hoffmann Summary:,Purpose: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood,brain barrier (BBB). MRP2 is absent in the transport-deficient (TR,) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR, rats compared with nonmutant (wild-type) Wistar rats. Methods: The expression of MRP2 and Pgp in brain and liver sections of TR, rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. Results: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR, rats. TR, rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR, rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. Conclusions: The data on TR, rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR, rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose. [source] Variable expression of CYP and Pgp genes in the human small intestineEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003M. Lindell Abstract Background ,The small intestine is receiving increased attention for its importance in drug metabolism. However, knowledge of the intervariability and regulation of the enzymes involved, cytochrome P450 and P-Glycoproteins (CYP and Pgp), is poor when compared with the corresponding hepatic enzymes. Methods ,The expression of eight different CYP genes and the Pgp were determined by reverse transcription polymerase chain reaction (RT-PCR) in 51 human duodenum biopsies. And the variability and correlation of expression was analyzed. Results ,Extensive interindividual variability was found in the expression of most of the genes. Only CYP2C9, CYP3A4 and Pgp were found in all samples. CYP1A2, CYP2A6 and CYP2E1 exhibited the highest interindividual variability. No strong correlation of expression existed between the genes. But a highly significant correlation was found between CYP2D6/1A2, 2D6/2E1, 1A2/2E1 and 2B6/2C9. Acetylsalicylic acid and omeprazole significantly increased the expression of CYPs 2A6, 2E1 and 3A4, respectively. Conclusions ,Extensive interindividual variability is characteristic for the expression of drug-metabolizing CYP and Pgp genes in human duodenum, and external factors such as drugs may further increase the variability. It is possible that the large interindividual variability may lead to variable bioavailability of orally used drugs and hence complicate optimal drug therapy, especially for drugs with a small therapeutic window. Elucidation of factors contributing to clinically important variances warrants further investigation. [source] | ||||||||||||||||||||||||||||||||||||||||