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PubMed1995

Analysis of metallothionein isoforms by capillary electrophoresis: optimisation of protein separation conditions using micellar electrokinetic capillary chromatography.

Capillary electrophoresis (CE) techniques have been successfully applied to the separation of metallothionein (MT) isoforms and have proved to be rapid, practical and economical. Study of a variety of different electrolytes and capillaries has shown that electrolyte buffer composition and capillary wall surface modifications can have considerable influence on isoform separation and resolution. Ionic surfactants such as sodium dodecyl sulphate (SDS) form micelles at elevated concentrations and the partitioning of molecules between the hydrophobic micelle phase and the aqueous phase and their resulting migration in an electric field is the basis of the technique known as micellar electrokinetic capillary chromatography (MECC). In the present work, we have used sheep and rabbit MT to optimise MECC conditions for analysis of MT isoforms. Capillaries of 57 cm gave much better separations than shorter columns although analysis times were increased to about 12 min. Changing the buffer and SDS concentration or the pH affected the selectivity of isoform separation and up to 5 isoforms in sheep MT and 6 in rabbit MT were completely or partially resolved. Comparing different diameter capillaries we conclude that 25 microns I.D. columns give better separations than 50 or 75 microns I.D. columns although sensitivity is reduced by a factor of about 3 and 5, respectively. Using our MECC conditions, columns coated with C1 or C18 hydrophobic material were not found to be useful in improving MT separation or resolution although further evaluation of these columns is in progress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Endothelium as a transducing surface.

Endothelial cells responses to a variety of agonists include release of endothelium dependent vasodilators, such as endothelium dependent relaxing factor (EDRF) and prostacyclin (PGI2). These substances act on vascular smooth muscle to cause relaxation and also have potent anti-aggregatory effects on platelets. A study of the mechanisms of signal transduction involved in these processes was undertaken. An investigation of intracellular calcium using FURA-2 and INDO-1 loaded endothelial cells shows transient elevation in response to vasodilator agonists. The calcium content of endothelial cells calculated using 45Ca flux techniques is increased in response to bradykinin and thrombin. Receptor activation leads to increased phosphoinositide turnover in endothelial cells and activates protein kinase C, the latter may be involved in feedback regulation. Patch clamp studies have demonstrated receptor-operated ionic channels in the endothelial cell membrane. Thus, intracellular calcium concentration is elevated in response to receptor activation, both as a result of liberation of calcium from intracellular stores and calcium entry from extracellular sources. Endothelial cells also respond to particulate stimuli. They can selectively bind and phagocytize bacteria. Phagocytosis leads to generation of superoxide aionin, a process which also seems to be controlled by elevation of intracellular calcium and activation of protein kinase C. In addition phagocytosis activates endothelial cells resulting in increased migration, division and further phagocytosis. All in all, the plethora of different endothelial responses to a variety of stimuli suggests a complex and multipotent cell type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Technetium-99, iodine-129 and tritium in the waters of the Savannah River Site.

Surface water samples were collected from streams on and around the Savannah River Site (SRS) to assess current 3H, 99Tc, and 129I concentrations in the water. The SRS is a nuclear facility operated by Westinghouse Savannah River Company for the US Department of Energy. Water quality parameters were measured at the time of collection using field portable instrumentation. The tritium activity was determined by liquid scintillation spectrometry. The isotopes, 99Tc and 129I, were determined by isotope dilution/inductively coupled plasma-mass spectrometry (D.M. Beals, Determination of technetium-99 in aqueous samples by isotope dilution inductively coupled plasma-mass spectrometry. Presented at the 3rd International Conference on Nuclear and Radiochemistry, Vienna, September 1992, unpublished data; D.M. Beals, P. Chastagner and P.K. Turner, Analysis of iodine-129 in aqueous samples by inductively coupled plasma-mass spectrometry. Presented at the 38th Annual Conference on Bioassay, Analytical and Environmental Radiochemistry, Santa Fe, NM, November 1992). Elevated activities of 3H, 99Tc, and 129I were found in some surface streams of the SRS, principally due to migration of ground water from beneath old seepage basins, however the levels in the waters leaving the SRS are well below any regulatory guidelines.

Fresh Water↗
PubMed1990

Alpha-difluoromethylornithine resistance in Leishmania donovani is associated with increased ornithine decarboxylase activity.

The promastigote form of Leishmania donovani is sensitive to growth inhibition by DL-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), the first enzyme of the polyamine biosynthetic pathway, with an EC50 value of approximately 30 microM. Exposure of a wild type (DI700) cell population to gradually increasing concentrations of DFMO resulted in the selection of a strain of Leishmania, DFMO-10, which was capable of proliferating in 10 mM DFMO. DFMO-10 cells possessed an EC50 value for DFMO greater than 4 mM, and were cross-resistant to alpha-methylornithine, alpha-monofluoromethyl-3,4-dehydroornithine methyl ester, and delta-methyl-acetylenic putrescine, three other inhibitors of ODC activity. DI700 and DFMO-10 cells accumulated and/or transported [3H]DFMO and a spectrum of basic, neutral, and acidic amino acids at comparative rates. However, the DFMO-resistant Leishmania, if suspended in culture medium in the absence of DFMO for several days, expressed up to 15-fold greater levels of ODC activity than did wild-type cells. The overexpressed ODC in mutant cells appeared kinetically normal, since the ODC activities from DI700 and DFMO-10 cells possessed similar apparent Km values for ornithine and were equally sensitive to inactivation by DFMO. Incubation of extracts of DFMO-10 cells, but not of wild-type parental cells, with [3H]DFMO for 1 h resulted in the labeling of a polypeptide, presumably ODC, which migrated with a molecular weight of 76,000 +/- 4000 on SDS-gel electrophoretograms. As a consequence of the elevated ODC activities, the levels of putrescine in mutant cells released from DFMO exposure were also elevated by about 15-fold over those of wild-type cells, although spermidine levels in DI700 and DFMO-10 cells were similar. In the absence of prolonged selective pressure, the resistance to DFMO, the ODC activity, and the putrescine levels of DFMO-10 cells all returned to those of wild type cells, indicating that the mutant phenotype of DFMO-selected L. donovani was unstable.

Affinity Labels↗
PubMed2002

Hematological responses to hematozoa in North American and neotropical songbirds.

Hematocrit (Hct), hemoglobin concentration, RBC count, and blood parasite loads (Plasmodium, Leucocytozoon, Haemoproteus, Trypanosoma, microfilariae) were measured in 688 passerine birds captured at four sites in the US and Belize, C.A., to assess physiological consequences of parasitemia. Parasite loads were low overall: 80% of birds had <5 parasites/10000 RBCs; median infection intensity was 1 per 10000 RBCs. Infection prevalence and intensity were higher in Belize than in the US. Analyses across and within taxa revealed no significant linear correlations between hematology values and parasite load, though infected birds were more likely to be anemic. Neotropical migrants reaching the southern US had lower parasite loads than migrants wintering in Belize. Mean Hct was significantly elevated among infected migrants (but not uninfected migrants) reaching the US relative to migrants in Belize. Long-distance migration thus appears to act as a filter for heavily parasitized and anemic birds. Geographic and seasonal variations in hematology indices were similar within and between taxa, suggesting that community-wide factors, rather than phylogenetic attributes or species-specific pathogens, account for the majority of hematological variation. The low parasite loads and weak correlation between parasite load and hematology indices have implications for attempts to test the version of the 'good genes' hypothesis.

Animal Migration↗
PubMed2001

Mutagen sensitivity of nasopharyngeal cancer patients.

Primary nasopharyngeal carcinomas (NPCs) may be of various types, including squamous cell carcinomas, undifferentiated carcinomas, and lymphoepitheliomas. Tumor initiation has been linked to the Epstein-Barr virus and, in some geographical regions, to alimentary factors. Possible hereditary components for the appearance of NPCs have not yet been clearly identified. In this study, genetic sensitivity to the genotoxic effects of carcinogenic xenobiotics as an endogenous risk factor of tumor initiation was investigated. The single cell microgel electrophoresis assay was used to quantify chemically-induced DNA damage in lymphocytes of 30 NPC patients and 30 non-tumor donors. The xenobiotics investigated were N'-nitrosodiethylamine, sodium dichromate, and nickel sulphate, with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) as positive and negative controls, respectively. The extent of DNA migration in the solvent control cultures was not significantly different between the two groups (1.2+/-0.5 mean Olive tail moment and standard deviation of 30 individuals for NPC patients; 1.1+/-0.4 for non-tumor donors). With constant exposure and electrophoretic conditions, genotoxic effects of varying degrees were induced by the different xenobiotics in tumor and non-tumor patients (nickel sulphate: 7.1+/-2.5 for NPC patients and 5.9+/-1.6 for non-tumor donors; sodium dichromate: 18.1+/-5.3 for NPC patients and 16.2+/-5.4 for non-tumor donors; MNNG: 47.8+/-13.3 for NPC patients and 52.7+/-13.6 for non-tumor donors). Only N'-nitrosodiethylamine proved to induce significantly more DNA migration in lymphocytes of tumor patients (9.8+/-3.1) as compared to non-tumor patients (8.2+/-2.3). Although for sodium dichromate the degree of DNA migration did not significantly differ, variability in migration patterns proved to be lower in the tumor group. Mutagen sensitivity of NPC patients was shown to be elevated for a selected xenobiotic, whereas a general elevation of DNA fragility was not present. Further studies on mutagen sensitivity as an endogenous risk factor influencing the susceptibility of patients at the time of first diagnosis of nasopharyngeal carcinomas are warranted.

Adult↗
PubMed2005

X-chromosome as a marker for population history: linkage disequilibrium and haplotype study in Eurasian populations.

Linkage disequilibrium (LD) structure is still unpredictable because the interplay of regional recombination rate and demographic history is poorly understood. We have compared the distribution of LD across two genomic regions differing in crossing-over activity -- Xq13 (0.166 cM/Mb) and Xp22 (1.3 cM/Mb) -- in 15 Eurasian populations. Demographic events predicted to increase the LD level -- genetic drift, bottleneck and admixture - had a very strong impact on extent and patterns of regional LD across Xq13 compared to Xp22. The haplotype distribution of the DXS1225-DXS8082 microsatellites from Xq13 exhibiting strong association in all populations was remarkably influenced by population history. European populations shared one common haplotype with a frequency of 25-40%. The Volga-Ural populations studied, living at the geographic borderline of Europe, showed elevated LD as well as harboring a significant fraction of haplotypes originating from East Asia, thus reflecting their past migrations and admixture. In the young Kuusamo isolate from Finland, a bottleneck has led to allelic associations between loci and shifted the haplotype distribution, but has much less affected single microsatellite allele frequencies compared to the main Finnish population. The data show that the footprint of a demographic event is longer preserved in haplotype distribution within a region of low crossing-over rate, than in the information content of a single marker, or between actively recombining markers. As the knowledge of LD patterns is often chosen to assist association mapping of common disease, our conclusions emphasize the importance of understanding the history, structure and variation of a study population.

Asia↗
PubMed2002

Increased spreading, Rac/p21-activated kinase (PAK) activity, and compromised cell motility in cells deficient in vasodilator-stimulated phosphoprotein (VASP).

Ena/VASP (Drosophila Enabled/vasodilator-stimulated phosphoprotein) proteins are key regulators that promote or inhibit actin-based motility, cell adhesion, and various aspects of axon guidance. However, a conclusive concept of Ena/VASP functions remains elusive. Here, we report that VASP-deficient fibroblasts, despite normal mammalian Enabled (Mena) and Ena-VASP-like (Evl) expression levels, are highly spread. VASP(-/-) cells cover about twice the substrate surface area as wild type cells, while cell volumes are unchanged. In accordance with these observations, activation of the Rac/p21-activated kinase (PAK) pathway, a crucial element in the regulation of cell spreading, is markedly enhanced in VASP(-/-) cells. Thus, in the absence of VASP Rac activation is dramatically prolonged, and PAK activity is elevated after stimulation with platelet-derived growth factor or serum, respectively. Moreover, VASP-deficient cells show compromised migration and reorientation in a wound healing assay. Collectively, our results reveal a VASP-dependent modulation of the Rac/PAK pathway and Rac/PAK-regulated processes, like cell motility and polarization.

Animals↗
PubMed2003

Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma.

Src family kinases are major regulators of various integrin-mediated biological processes, although their functional roles and substrates in cancer metastasis are unknown. We explored the roles of Src family tyrosine kinases in cell migration and the spread of K-1735 murine melanoma cell lines with low or high metastatic potential. Corresponding to elevated cell motility and spreading ability, Fyn was selectively activated among Src family kinases, and the cell motility was blocked by an inhibitor of Src family kinases. Significant tyrosine phosphorylation of cortactin, stable complex formation between activated Fyn and cortactin, and co-localization of cortactin with Fyn at cell membranes were all observed only in cells with high metastatic potential. Both integrin-mediated Fyn activation and hyperphosphorylation of cortactin were observed 2-5 h after stimulation in highly metastatic cells, and they required de novo protein synthesis. We demonstrate that cortactin is a specific substrate and cooperative effector of Fyn in integrin-mediated signaling processes regulating metastatic potential.

Animals↗
PubMed2004

The Brn-3b transcription factor regulates the growth, behavior, and invasiveness of human neuroblastoma cells in vitro and in vivo.

Neuroblastomas are the second most common solid tumor in children but the molecular mechanisms underlying the initiation and progression of this disease are poorly understood. We previously showed that the Brn-3b transcription factor is highly expressed in actively proliferating neuroblastoma cells but is significantly decreased when these cells are induced to differentiate. In this study, we analyzed the effects of manipulating Brn-3b levels in the human neuroblastoma cell line, IMR-32 and showed that constitutive overexpression of Brn-3b consistently increased cellular growth and proliferation in monolayer as well as in an anchorage-independent manner compared with controls whereas stably decreasing Brn-3b can reduce the rate of growth of these cells. Cells with high Brn-3b also fail to respond to growth inhibitory retinoic acid, as they continue to proliferate. Moreover, Brn-3b levels significantly modified tumor growth in vivo with elevated Brn-3b resulting in faster tumor growth in xenograft models whereas decreasing Brn-3b resulted in slower growth compared with controls. Interestingly, elevated Brn-3b levels also enhances the invasive capacity of these neuroblastoma cells with significantly larger numbers of migrating cells observed in overexpressing clones compared with controls. Because invasion and metastasis influence morbidity and mortality in neuroblastoma and so significantly affect the course and outcome of neuroblastomas, this finding is very important. Our results therefore suggest that Brn-3b transcription factor contributes to proliferation of neuroblastoma cells in vivo and in vitro but may also influence progression and/or invasion during tumorigenesis. It is possible that decreasing Brn-3b levels may reverse some effects on growth and proliferation of these cells.

Cell Adhesion↗
PubMed2000

Antiangiogenic gene therapy for cancer via systemic administration of adenoviral vectors expressing secretable endostatin.

A growing number of antiangiogenesis strategies have been investigated for the treatment of cancer and other angiogenesis-dependent diseases. One of the most promising strategies is to systemically administer one or more antiangiogenic proteins frequently enough to achieve a sufficient long-term steady state level of the protein(s) to achieve the maximum beneficial effect. However, the utility of this strategy is limited because of many technical difficulties, including obtaining both the quantity and quality of the protein(s) necessary for optimal therapeutic benefit. To overcome these difficulties, we hypothesized that a single administration of a replication-defective adenoviral vector expressing a secretable antiangiogenic protein could achieve an optimal long-term systemic concentration. We constructed a recombinant adenoviral vector, Av3mEndo, which encodes a secretable form of murine endostatin. We demonstrated secretion of endostatin from several cell lines transduced with Av3mEndo. Partially purified endostatin secreted from Av3mEndo-transduced mammalian cells was shown to potently inhibit endothelial cell migration in vitro. A single intravenous administration of Av3mEndo in mice was shown to result in (1) prolonged and elevated levels of circulating endostatin, (2) partial inhibition of VEGF-induced angiogenesis in a VEGF implant angiogenesis model, and (3) prolonged survival and in 25% of mice the complete prevention of tumor growth in a prophylactic human colon/liver metastasis xenograft murine model. These results support our contention that adenoviral vector-mediated expression of an antiangiogenic protein(s) represents an attractive therapeutic approach to cancer and other angiogenesis-dependent diseases.

Adenoviridae↗
PubMed2004

Thrombin and its protease-activated receptor-1 (PAR1) participate in the endothelial-mesenchymal transdifferentiation process.

The serine protease thrombin, independently of its participation in hemostasis and thrombosis, has been involved in tissue repair and remodeling, embryogenesis, angiogenesis, and development and progression of atherosclerosis. Many of these functions appear to be mediated by specific thrombin receptors, particularly the protease-activated receptor-1 (PAR1). In this study, we investigated whether both thrombin and PAR1 were present in the aortic wall of chicken embryos at days 11 and 12 of development. We found that PAR1 was limited to some cells of the intimal thickening and the inner media, whereas thrombin appeared distributed across the aortic wall. We also investigated whether PAR1 was present during endothelial-mesenchymal transdifferentiation (EMT) in vitro. A moderate immunoreactivity was detected in the monolayer of endothelial cells. In contrast, a strong cytoplasmic immunoreactivity was observed in the detaching and migrating cells and those that had acquired mesenchymal characteristics. This PAR1 expression was confirmed by flow cytometry. In this study, the addition of thrombin to arrested endothelial cell cultures was assessed. We found that thrombin stimulated endothelial cell spreading and migration, as no migrating cells were observed in serum-free medium (SFM) condition. Immunolocalization of PAR1 in the thrombin-treated cultures showed strong cytoplasmic immunoreactivity in the monolayers and in spreading and migrating cells, whereas in the SFM condition undetectable PAR1 immunoreactivity was observed. Flow cytometry of these cultures revealed an elevated expression of PAR1 in the presence of thrombin, in contrast to that detected in SFM and complete medium. These data indicate that both thrombin and PAR1 are involved in the remodeling of the aortic wall and intimal thickening formation, and in the endothelial-mesenchymal transdifferentiation process.

Animals↗
PubMed1993

Clinical gnathostomiasis: case report and review of the English-language literature.

Human gnathostomiasis is most frequently caused by the nematode Gnathostoma spinigerum. This disease is endemic to Southeast Asia, particularly Thailand and Japan. The clinical presentation is most commonly characterized by localized, intermittent, migratory swellings of the skin and subcutaneous tissues, often in association with localized pain, pruritus, and erythema. Since this worm can migrate to deeper tissues, any organ system may become involved. Characteristically, patients with gnathostomiasis have a moderate to severe elevation of the peripheral eosinophil count, with values not uncommonly exceeding 50% of the total white blood cell count. With modern-day travel and immigration, cases of gnathostomiasis are being diagnosed with increased frequency in the United States. Because of its rarity in this country, however, gnathostomiasis often is not included in an initial differential diagnosis despite the characteristic triad of intermittent migratory swelling, a history of travel to Southeast Asia, and eosinophilia. We report a case of cutaneous gnathostomiasis diagnosed in the United States, and we present a clinical review of the English-language literature on human gnathostomiasis.

Adult↗
PubMed1998

Fibronectin and the extracellular matrix in the perforating disorders of the skin.

Despite detailed microscopic descriptions and clinical observation, little is known regarding the pathogenesis of the perforating disorders of skin, which have traditionally been subdivided into numerous microscopic entities associated with various clinical settings. An increasing body of evidence now suggests that the perforating disorders of skin are akin, and may constitute an expanded single pathologic entity. Each of the classic perforating disorders of skin, including elastosis perforans serpiginosa, perforating folliculitis, reactive perforating collagenosis, Kyrle's disease, and perforating disorder of uremia, have been shown to extrude collagen, elastin, and related extracellular matrix components through the epidermis. Considering a shared pathogenic mechanism among these entities, we explored the possible role of the extracellular matrix, in particular fibronectin, in perforating disorders of skin. Using immunohistochemical and serum determinations of extracellular matrix constituents, including fibronectin, collagen type IV, laminin, and tenascin, we showed consistent serum elevation and/or deposition of fibronectin, in each case, without a commensurate increase in laminin, collagen type IV, and tenascin. We propose that elevated serum and tissue concentrations of fibronectin may be responsible for inciting, in a physiologically aberrant manner, increased epithelial migration and proliferation culminating in perforation.

Adolescent↗
PubMed2001

Effects of Orengedoku-to and Senkanmeimoku-to, traditional herbal medicines, on the experimental elevation of aqueous flare in pigmented rabbits.

We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese) and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS) were injected into the ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w) Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05) elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P < 0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku-to and Senkanmeimoku-to may migrate some forms of uveitis.

Animals↗
PubMed2002

Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury.

The use of positive pressure mechanical ventilation can cause ventilator-induced lung injury (VILI). We hypothesized that hyperoxia in combination with large tidal volumes (VT) would accentuate noncardiogenic edema and neutrophil infiltration in VILI and be dependent on stretch-induced macrophage inflammatory protein-2 (MIP-2) production. In rats ventilated with VT 20 ml/kg, there was pulmonary edema formation that was significantly increased by hyperoxia. Total lung neutrophil infiltration and MIP-2 in bronchoalveolar lavage (BAL) fluid were significantly elevated, in animals exposed to high VT both on room air (RA) and with hyperoxia. Hyperoxia markedly augmented the migration of neutrophils into the alveoli. Anti-MIP-2 antibody blocked migration of neutrophils into the alveoli in RA by 51% and with hyperoxia by 65%. We concluded that neutrophil migration into the alveoli was dependent on stretch-induced MIP-2 production. Hyperoxia significantly increased edema formation and neutrophil migration into the alveoli with VT 20 ml/kg, although BAL MIP-2 levels were nearly identical to VT 20 ml/kg with RA, suggesting that other mechanisms may be involved in hyperoxia-augmented neutrophil alveolar content in VILI.

Animals↗
PubMed2005

Crk-associated substrate tyrosine phosphorylation sites are critical for invasion and metastasis of SRC-transformed cells.

Crk-associated substrate (CAS, p130Cas) is a major tyrosine phosphorylated protein in cells transformed by v-crk and v-src oncogenes. We recently reported that reexpression of CAS in CAS-deficient mouse embryo fibroblasts transformed by oncogenic Src promoted an invasive phenotype associated with enhanced cell migration through Matrigel, organization of actin into large podosome ring and belt structures, activation of matrix metalloproteinase-2, and elevated tyrosine phosphorylation of the focal adhesion proteins FAK and paxillin. We have now extended these studies to examine the mechanism by which CAS achieves these changes and to evaluate the potential role for CAS in promoting in vivo tumor growth and metastasis. Whereas the presence or absence of CAS did not alter the primary growth of subcutaneous-injected Src-transformed mouse embryo fibroblasts, CAS expression was required to promote lung metastasis following removal of the primary tumor. The substrate domain YxxP tyrosines, the major sites of CAS phosphorylation by Src that mediate interactions with Crk, were found to be critical for promoting both invasive and metastatic properties of the cells. The ability of CAS to promote Matrigel invasion, formation of large podosome structures, and tyrosine phosphorylation of Src substrates, including FAK, paxillin, and cortactin, was also strictly dependent on the YxxP tyrosines. In contrast, matrix metalloproteinase-2 activation was most dependent on the CAS SH3 domain, whereas the substrate domain YxxP sites also contributed to this property. Thus multiple CAS-mediated signaling events are implicated in promoting invasive and metastatic properties of Src-transformed cells.

Animals↗
PubMed1995

In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes.

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.

Animals↗