340 research outputs found
Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones
No full textTo verify whether PTH acts on bone-specific blood vessels and on cells surrounding these blood vessels, 6-week-old male mice were subjected to vehicle (control group) or hPTH [1-34] (20 mu g/kg/day, PTH group) injections for 2 weeks. Femoral metaphyses were used for histochemical and immunohistochemical studies. In control metaphyses, endomucin-positive blood vessels were abundant, but alpha SMA-reactive blood vessels were scarce. In the PTH-administered mice, the lumen of endomucin-positive blood vessels was markedly enlarged. Moreover, many alpha SMA-positive cells were evident near the blood vessels, and seemed to derive from those vessels. These alpha SMA-positive cells neighboring the blood vessels showed features of mesenchymal stromal cells, such as immunopositivity for c-kit and tissue nonspecific alkaline phosphatase (TNALP). Thus, PTH administration increased the population of perivascular/stromal cells positive for alpha SMA and c-kit, which were likely committed to the osteoblastic lineage. To understand the cellular events that led to increased numbers and size of bone-specific blood vessels, we performed immunohistochemical studies for PTH/PTHrP receptor and VEGF. After PTH administration, PTH/PTHrP receptor, VEGF and its receptor flk-1 were consistently identified in both osteoblasts and blood vessels (endothelial cells and surrounding perivascular cells). Our findings suggest that exogenous PTH increases the number and size of bone-specific blood vessels while fostering perivascular/stromal cells positive for alpha SMA/TNALP/c-kit
Histochemical examination of blood vessels in murine femora with intermittent PTH administration
No full textObjective: To verify the biological effects of parathyroid hormone (PTH) on the blood vessels in the bone, this study aimed to investigate histological alterations in endomucin-positive blood vessels and perivascular cells in murine femora after intermittent PTH administration. For comparison with blood vessels in the bone, we examined the distribution of endomucin-positive blood vessels and surrounding aSMAimmunoreactive perivascular cells in the liver, kidney, and aorta with or without PTH administration. Methods: Six-week-old male C57BL/6J mice received hPTH [1-34] or vehicle for two weeks. All mice were fixed with a paraformaldehyde solution after euthanasia, and the right femora, kidney, liver, and aorta were extracted for immunohistochemical analysis of endomucin, aSMA, ephrinB2, EphB4, and HIF1a. Light microscopic observations of semi-thin sections and transmission electron microscopic (TEM) observations of ultra-thin sections were performed on the left femora. Results: After intermittent PTH administration, aSMA-reactive/ephrinB2-positive stromal cells appeared around endomucin-positive/EphB4-immunoreactive blood vessels in the bone. In addition, intense immunoreactivities of EphB4 and HIF1a were seen in vascular endothelial cells after the PTH treatment. Several stromal cells surrounding PTH-treated blood vessels exhibited well-developed rough endoplasmic reticulum under TEM observations. In contrast to bone tissues, aSMA-positive stromal cells did not increase around the endomucin-positive blood vessels in the kidney, liver, or aorta, even after PTH administration. Conclusion: These findings show that intermittent PTH administration increases aSMA-reactive/ephrinB2-positive perivascular stromal cells in bone tissue but not in the kidney, liver, or aorta, suggesting that PTH preferentially affects blood vessels in the bone. (c) 2022 Published by Elsevier B.V. on behalf of Japanese Association for Oral Biology
Immunocytochemical distribution of PTH immunoreactivity in vertebrate brains
No full text Immunoreactive (IR) cell bodies, reacting with an antiserum specific for the 48-64 region of bovine parathyroid hormone (PTH), were detected in the brains of primitive vertebrates (hagfish), bullfrogs, and higher vertebrates (mice). In each species the IR perikarya were located in the preoptic region, although the precise location and abundance of IR perikarya differed among species. Fiber tracts from these IR perikarya were traced to the neurohypophysis in the hagfish but only to the median eminence in the bullfrog and mouse, where the axonal terminals were in close proximity to hypophyseal portal blood vessels. These results suggest that a novel PTH-like peptidergic system, similar to those secreting hypophysiotropic-releasing factors, is present in the vertebrate brain. </jats:p
On high-order iterative schemes for the matrix pth root avoiding the use of inverses
No full textThis paper is devoted to the approximation of matrix pth roots. We present and analyze a family of algorithms free of inverses. The method is a combination of two families of iterative methods. The first one gives an approximation of the matrix inverse. The second family computes, using the first method, an approximation of the matrix pth root. We analyze the computational cost and the convergence of this family of methods. Finally, we introduce several numerical examples in order to check the performance of this combination of schemes. We conclude that the method without inverse emerges as a good alternative since a similar numerical behavior with smaller computational cost is obtained.The research of the authors S.A. and S.B. was funded in part by Programa de Apoyo a la investigación de la Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia 20928/PI/18 and by PID2019-108336GB-100 (MINECO/FEDER). The research of the author M.Á.H.-V. was supported in part by Spanish MCINN PGC2018-095896-B-C21. The research of the author Á.A.M. was funded in part by Programa de Apoyo a la investigación de la Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia 20928/PI/18 and by Spanish MCINN PGC2018-095896-B-C21
LASER SPECTROSCOPY OF PdH/PdD AND PtH/PtD
No full textAuthor Institution: Department of Chemistry, Massachusetts Institute of Technology; Department of Chemistry, Arizona State University; Department of Chemistry, Massachusetts Institute of TechnologyWe have recently observed several new bands in the electronic spectrum of PtH/PtD and reanalyzed several other bands in both PtH/PtD and PdH/PdD by laser excitation spectroscopy in the region 23,800-. Sub-Doppler intermodulated fluorescence measurements also have been performed on the strong (1,0) and (0,0) bands of PtH and hyperfine constants for both the ground and excited states have been determined. In addition to discussing these results, we will present an electronic structure model, based on the supermultiplet and augmented by the atomic zero-order energy separation, which we have developed to explain the position and ordering of the low-lying states in the homologous series consisting of NiH, PdH, and PtH
FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line
No full textThe signaling axis comprised by the parathyroid hormone (PTH)-related peptide (PTHrP), the PTH/PTHrP receptor and the fibroblast growth factor receptor 3 (FGFR3) plays a central role in chondrocyte proliferation. The Indian hedgehog (IHH) gene is normally expressed in early hypertrophic chondrocytes, and its negative feedback loop was shown to regulate PTH/PTHrP receptor signaling. In this study, we examined the regulation of PTH/PTHrP receptor gene expression in a FGFR3-transfected chondrocytic cell line, CFK2. Expression of IHH could not be verified on these cells, with consequent absence of hypertrophic differentiation. Also, expression of the PTH/PTHrP receptor (75% reduction of total mRNA) and the PTHrP (50% reduction) genes was reduced in CFK2 cells transfected with FGFR3 cDNA. Interestingly, we verified significant reduction in cell growth and increased apoptosis in the transfected cells. STAT1 was detected in the nuclei of the CFK2 cells transfected with FGFR3 cDNA, indicating predominance of the JAK/STAT signaling pathway. The reduction in PTH/PTHrP receptor gene in CFK2 cells over-expressing FGFR3 was partially blocked by treatment with an inhibitor of JAK3 (WHI-P131), but not with an inhibitor of MAPK (SB203580) or JAK2 (AG490). Altogether, these findings suggest that FGFR3 down-regulates PTH/PTHrP receptor gene expression via the JAK/STAT signaling in chondrocytic cells
General Programs for Least pth and Near Minimax Approximation
No full textTitle: General Programs for Least pth and Near Minimax Approximation, Author: Jadranka K. Rizoniko-Popovic, Location: ThodeUser-oriented computer programs in FORTRAN IV for discrete least pth approximation with a single specified function, and more generalized discrete least pth approximation with various specifications, which may also be used for nonlinear programming, are presented. Values of p up to 10^6 can be used successfully in conjunction with efficient gradient minimization algorithms such as the Fletcher-Powell method and a recent method due to Fletcher. It has already been demonstrated how efficiently extremely near minimax results can be achieved on a discrete set of sample points using this approach and the programs written verify this. The programs may be applied to a wide variety of design problems with a wide range of specifications. They are suitable for electrical network and system design and such problems as filter design.ThesisMaster of Engineering (ME
Suppression of the Pth(Ts) phenotype mediated by the overproduction of tRNA maintains moderate levels of the Pth(Ts) protein
No full text<p><b>Copyright information:</b></p><p>Taken from "Excess of charged tRNA maintains low levels of peptidyl-tRNA hydrolase in (Ts) mutants at a non-permissive temperature"</p><p>Nucleic Acids Research 2006;34(5):1564-1570.</p><p>Published online 15 Mar 2006</p><p>PMCID:PMC1408313.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> () Depicts the cellular growth of the (Ts) mutant strain AA7852 separately transformed with pVH124 (ΔU, ΔV), pVH125 (U, ΔV) or pVH119 (U, V) incubated at different temperatures. Isolated colonies of the independent transformants were streaked onto LB-Ap plates and incubated overnight at the indicated temperatures. () Presents the immunodetection of Pth(Ts) in the (Ts) mutant strain AA7852 separately transformed with pVH124, pVH125, pVH119, ptRNACCA (X, R, T, M) or pTH2 (W) and grown at 32°C prior to transfer at time = 0 min at 41 or 43°C. The concentration of Pth(Ts) protein was estimated by immunoblot analysis. The left lane shows purified wild-type Pth protein, which migrates slightly faster in SDS–PAGE than the Pth(Ts) variant (arrowed) ()
Immunohistochemical and Morphometric Assessment on the Biological Function and Vascular Endothelial Cells in the Initial Process of Cortical Porosity in Mice With PTH Administration
No full textTo clarify the cellular mechanism of cortical porosity induced by intermittent parathyroid hormone (PTH) administration, we examined the femoral cortical bone of mice that received 40 mu g/kg/day (four times a day) human PTH (hPTH) (1-34). The PTH-driven cortical porosity initiated from the metaphyseal region and chronologically expanded toward the diaphysis. Alkaline phosphatase (ALP)-positive osteoblasts in the control mice covered the cortical surface, and endomucin-positive blood vessels were distant from these osteoblasts. In PTH-administered mice, endomucin-reactive blood vessels with TRAP-positive penetrated the ALP-positive osteoblast layer, invading the cortical bone. Statistically, the distance between endomucin-positive blood vessels and the cortical bone surface abated after PTH administration. Transmission electron microscopic observation demonstrated that vascular endothelial cells often pass through the flattened osteoblast layer and accompanied osteoclasts in the deep region of the cortical bone. The cell layers covering mature osteoblasts thickened with PTH administration and exhibited ALP, alpha-smooth muscle actin (alpha SMA), vascular cell adhesion molecule-1 (VCAM1), and receptor activator of NF-kappa B ligand (RANKL). Within these cell layers, osteoclasts were found near endomucin-reactive blood vessels. In PTH-administered femora, osteocytes secreted Dkk1, a Wnt inhibitor that affects angiogenesis, and blood vessels exhibited plasmalemma vesicle-associated protein, an angiogenic molecule. In summary, endomucin-positive blood vessels, when accompanied by osteoclasts in the ALP/alpha SMA/VCAM1/RANKL-reactive osteoblastic cell layers, invade the cortical bone, potentially due to the action of osteocyte-derived molecules such as DKK1
Vasodilation to PTH 1-84 in bone resistance arteries of rats occurs via endothelium-dependent, rather than endothelium-independent signaling
No full textParathyroid hormone (PTH) is a potent vasodilator, causing systemic hypotension. Previous investigations concluded that vasodilation to PTH in a variety of vascular beds occurs via inhibition of L-type calcium channels in smooth muscle cells. Further, removal of the endothelium in aortic strips and tail arteries did not inhibit relaxation to PTH, suggesting that vasodilation in these vessels does not require nitric oxide (NO) or vascular endothelial cells (Pang et al., 1985; Nickols 1987; Nickols et al., 1986; Crass et al., 1988). We have previously shown that PTH 1-84 augments vasodilation to ~52% of maximum diameter in the femoral principal nutrient artery (PNA; the primary conduit for blood flow to long bones). Further, vasodilation was nearly obliterated with blockade of NO production with the endothelial nitric oxide synthase inhibitor L-NAME, suggesting that vasodilation in the bone vasculature occurs exclusively via NO-mediated signaling. Thus, to confirm these findings, the purpose of this study was to determine whether vasodilation to PTH 1-84 occurs in the absence of endothelial cells. METHODS: Right femoral PNAs were dissected from 4 month-old male Wistar rats (453 g; n=6), denuded (i.e., removed of the endothelial cells) and cannulated on glass micropipettes. PNAs were considered adequately denuded if they dilated ≤ 20 µm to a bolus dose of acetylcholine (5x10-5 M). Vasodilation to PTH 1-84 (10-13 – 10-8 M) was assessed in the presence of 1) PSS buffer, 2) PSS buffer with L-NAME, and 3) PSS buffer with L-NAME + indomethacin (Indo; a cyclooxygenase inhibitor). To ensure that the smooth muscle cells were not damaged during endothelial cell removal, endothelium-independent vasodilation to sodium nitroprusside (SNP; 10-10 – 10-4) was determined. RESULTS: Vasodilation to cumulative doses of PTH 1-84 peaked at 5% of maximum diameter. Inhibition of NO production with L-NAME completely inhibited vasodilation and caused a slight vasoconstriction, while combined inhibition with L-NAME + Indo did not constrict the femoral PNA; however, neither response differed from the PTH 1-84 response. Vasodilation to SNP rose to 69% of maximal diameter, indicating that smooth muscle cell responsiveness was not altered with endothelial denudation. DISCUSSION: These preliminary data support our contention that vasodilation of the bone resistance vasculature occurs via endothelium-dependent, rather than endothelium-independent signaling pathways. This novel finding suggests that, contrary to vasodilator mechanisms in blood vessels from other tissue beds, bone blood vessels require the vascular endothelial cell lining for vasodilation to PTH 1-84.
Supported by NIH Grant 1R15AR062882-0
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