Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “elevational migration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources
PubMed2026

Crosstalk between S-nitrosylation and glycation defines a metabolic vulnerability in liver and renal cancers.

Metabolic reprogramming is a defining feature of cancer; however, how it contributes to therapeutic resistance remains incompletely understood. Here we show that loss of aldo-ketoreductase 1A1 (AKR1A1) in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) disrupts terminal glycolytic flux and lactate production through S-nitrosylation-mediated inhibition of pyruvate kinase, resulting in the accumulation of methylglyoxal (MGO). In multiple AKR1A1-deficient models, but not in those endogenously expressing the C423/424 A mutant of pyruvate kinase M2, elevated MGO triggers autophagic degradation of Kelch-like ECH-associated protein 1, leading to Nuclear factor erythroid 2-Related Factor 2 (NRF2) activation and transcriptional reprogramming. This NRF2-driven response enhances chemoresistance and promotes tumor cell migration, two hallmarks of aggressive cancer. Therapeutically, we demonstrate that pharmacological inhibition of the glyoxalase system-the major pathway for MGO detoxification-restores drug sensitivity in patient-derived cells and xenograft models, revealing a context-dependent metabolic vulnerability in AKR1A1 loss conditions. These findings identify AKR1A1 as a metabolic tumor suppressor and uncover crosstalk between S-nitrosylation and glycation as a key regulatory axis linking metabolic reprogramming to NRF2-driven therapy resistance, offering glyoxalase inhibition as a potential precision treatment strategy for RCC and HCC.

Humans↗
PubMed1976

Lymphocytes forming rosettes with sheep erythrocytes in metastatic pleural effusions.

Percentages of lymphocytes forming rosettes with sheep erythrocytes at 29 degrees C were determined in 10 cancer patients with metastases to the pleural cavity. Compared with normal controls, the patients showed a decreased proportion of rosette-forming cells (RFC) in the peripheral blood. The same patients had elevated levels of RFC in their metastatic pleural effusions. However, 2 patients with benign diseases had normal levels of RFC in their peripheral blood and pleural transudates. These observations suggested that in cancer patients some T-cells might migrate from the peripheral blood and accumulate in sites of tumor infiltration such as the pleural cavity.

Adult↗
PubMed1990

Failure of ovulation induction with pulsatile gonadotropin-releasing hormone and human menopausal gonadotropins in isolated gonadotropin deficiency.

A 30-year-old woman with primary amenorrhea, hypothalamic hypogonadism, decreased sense of smell, and primary infertility failed to respond to pulsatile exogenous gonadotropin-releasing hormone. In addition, failure to respond to stimulation with human menopausal gonadotropins was consistent with concomitant ovarian failure. Perturbation of normal cellular migration during embryogenesis in the regions of the olfactory placode, yolk sac, hindgut, and gonadal ridge may explain both the hypothalamic defect and ovarian failure experienced by this woman. She demonstrates that gonadal failure need not be accompanied by elevated gonadotropin levels; nor do low gonadotropin levels necessarily indicate potentially responsive ovaries. These findings are consistent with the coexistence of isolated gonadotropin deficiency and ovarian failure in the same individual.

Adult↗
PubMed2005

Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma.

We used a spheroid model of colon carcinoma to analyze integrin dynamics as a function of the epithelial-mesenchymal transition (EMT), a process that provides a paradigm for understanding how carcinoma cells acquire a more aggressive phenotype. This EMT involves transcriptional activation of the beta6 integrin subunit and a consequent induction of alphavbeta6 expression. This integrin enhances the tumorigenic properties of colon carcinoma, including activation of autocrine TGF-beta and migration on interstitial fibronectin. Importantly, this study validates the clinical relevance of the EMT. Kaplan-Meier analysis of beta6 expression in 488 colorectal carcinomas revealed a striking reduction in median survival time of patients with high beta6 expression. Elevated receptor expression did not simply reflect increasing tumor stage, since log-rank analysis showed a more significant impact on the survival of patients with early-stage, as opposed to late-stage, disease. Cox regression analysis confirmed that this integrin is an independent variable for these tumors. These findings define the alphavbeta6 integrin as an important risk factor for early-stage disease and a novel therapeutic candidate for colorectal cancer.

Animals↗
PubMed2005

ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow.

In vivo, leukocyte transendothelial migration (TEM) occurs at endothelial cell junctions (paracellular) and nonjunctional (transcellular) locations, whereas in vitro models report that TEM is mostly paracellular. The mechanisms that control the route of leukocyte TEM remain unknown. Here we tested the hypothesis that elevated intercellular adhesion molecule-1 (ICAM-1) expression regulates the location of polymorphonuclear leukocyte (PMN) TEM. We used an in vitro flow model of tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelium cells (HUVECs) or an HUVEC cell line transfected with ICAM-1GFP (green fluorescent protein) and live-cell fluorescence microscopy to quantify the location of PMN adhesion and TEM. We observed robust transcellular TEM with TNF-alpha-activated HUVECs and ICAM-1GFP immortalized HUVECS (iHUVECs). In contrast, primary CD3+ T lymphocytes exclusively used a paracellular route. Endothelial ICAM-1 was identified as essential for both paracellular and transcellular PMN transmigration, and interfering with ICAM-1 cytoplasmic tail function preferentially reduced transcellular TEM. We also found that ICAM-1 surface density and distribution as well as endothelial cell shape contributed to transcellular TEM. In summary, ICAM-1 promotes junctional and nonjunctional TEM across inflamed vascular endothelium via distinct cytoplasmic tail associations.

Amino Acid Sequence↗
PubMed1997

A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil recruitment in guinea pig skin.

The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibit eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhibitors rolipram, RP 73401 and CDP 840 on allergic and PAF-induced eosinophil recruitment. Rolipram and RP 73401 were equally effective and potent when given by the oral route and much more active than the PDE4 inhibitor CDP 840. We suggest that this guinea pig model of allergic and mediator-induced eosinophil recruitment is both a sensitive and simple tool to test the efficacy and potency of PDE4 inhibitors in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

[Extracorporeal lithotripsy of biliary lithiasis. 160 patients treated with an EDAP apparatus].

Since February 1987, we have been using extracorporeal lithotripsy for certain cases of chronic biliary lithiasis, using an EDAP lithotripter. The technique is reserved for patients with less than four radiotransparent, or partially calcified calculi, less than 25 mm in size, within the context of a functioning gall bladder with no evidence of lithiasis in the C.B.D. Dissolution of the fragments after lithotripsy is ensured by bile salts, this treatment being continued for at least 3 months after the gall bladder has been completely cleared. 160 patients were treated using a total of 181 treatment sessions. Hospitalisation lasted on average 3 days, 1/5th of the patients suffered right hypochondrial pain and nausea for 24 hours. 17% of patients showed a transient elevation in alkaline phosphatase and 12% an elevation in amylase after the procedure. The rate of gall bladder clearance was 24% at 1 month, 40.7% at 3 months ans 50% at 1 year. 11 cholecystectomies were carried out (6.8%), 8 of which were essential. Bile duct migration occurred in 2 cases and produced oedematous pancreatitis in one case. Recurrent lithiasis was noted in 4 cases between 6 and 18 months after gall bladder clearance. 75% of cured patients had a single, radiotransparent stone less than 20 mm in diameter.

Adult↗
PubMed1998

Cancer risk among Scandinavian immigrants in the US and Scandinavian residents compared with US whites, 1973-89.

Studies of migrants can generate hypotheses on the aetiology of cancer. Such studies are most informative when cancer incidence data are available both in the source and host country. We compared the incidence rate ratio of cancers (stomach, lung, female breast, colorectal and prostate) in Scandinavian immigrants to the US to US-born whites, using data from the SEER registry, 1973-89. Odds ratios (OR) for cancer sites in relation to birthplace were estimated using logistic regression. We also compared rate ratios (RR) for Scandinavian and US residents, using Poisson regression. Compared with US whites, most Scandinavian migrant groups had elevated OR for stomach cancer (1.58 to 3.92), and lower OR for lung cancer (0.38 to 0.88). Similarly, compared with US whites, residents of most Scandinavian countries had elevated RR for stomach cancer (1.47 to 3.33) and lower RR for lung cancer (0.27 to 0.97). Therefore, risk factors for lung and stomach cancers, such as smoking habits and Helicobacter pylori infection, respectively, may have been retained upon migration. Risks for breast, colorectal and prostate cancer among immigrants approached risks in the US (contrasting Scandinavian risks) suggesting assimilation of environmental and/or lifestyle factors.

Adolescent↗
PubMed2001

Neuronal regeneration in the cerebellum of adult teleost fish, Apteronotus leptorhynchus: guidance of migrating young cells by radial glia.

In contrast to mammals, adult fish exhibit an enormous potential to replace injured brain neurons by newly generated ones. In the present study, the role of radial glia, identified by immunostaining against fibrillary acidic protein (GFAP), was examined in this process of neuronal regeneration. Approximately 8 days after application of a mechanical lesion to the corpus cerebelli in the teleost fish Apteronotus leptorhynchus, the areal density of radial glial fibers increased markedly in the ipsilateral dorsal molecular layer compared to shorter survival times, or to the densities found in the intact brain or in the hemisphere contralateral to the lesion. This density remained elevated throughout the time period of up to 100 days examined. The increase in fiber density was followed approximately 2 days later by a rise in the areal density of young cells, characterized by labeling with the nuclear dye DAPI, in the ipsilateral dorsal molecular layer. Based on this remarkable spatio-temporal correlation, and the frequently observed close apposition of elongated young cells to radial glial fibers, we hypothesize that radial glia play an important role in the guidance of migrating young cells from their proliferation zones to the site of lesion where regeneration takes place.

Age Factors↗
PubMed2003

Avian migration phenology and global climate change.

There is mounting evidence that global climate change has extended growing seasons, changed distribution patterns, and altered the phenology of flowering, breeding, and migration. For migratory birds, the timing of arrival on breeding territories and over-wintering grounds is a key determinant of reproductive success, survivorship, and fitness. But we know little of the factors controlling earlier passage in long-distance migrants. Over the past 30 years in Oxfordshire, U.K., the average arrival and departure dates of 20 migrant bird species have both advanced by 8 days; consequently, the overall residence time in Oxfordshire has remained unchanged. The timing of arrival has advanced in relation to increasing winter temperatures in sub-Saharan Africa, whereas the timing of departure has advanced after elevated summer temperatures in Oxfordshire. This finding demonstrates that migratory phenology is quite likely to be affected by global climate change and links events in tropical winter quarters with those in temperate breeding areas.

Africa South of the Sahara↗
PubMed1995

Unwinding of closed circular DNA by the Escherichia coli RuvA and RuvB recombination/repair proteins.

The RuvA and RuvB proteins of Escherichia coli promote the branch migration of Holliday junctions during genetic recombination and the recombinational repair of damaged DNA. Using a topological assay that measures the underwinding of covalently closed duplex DNA, we find that RuvA and RuvB promote the transient unwinding of relaxed or supercoiled DNA. Detection of unwinding by RuvAB requires the presence of ATP and a non-hydrolysable ATP analogue (ATP gamma S), and was not observed in the presence of ATP or ATP gamma S alone. These results indicate that RuvAB catalyse the unwinding and rewinding of duplex DNA via an intermediate that can be stabilised by the presence a non-hydrolysable cofactor. At elevated concentrations of Mg2+ (12 to 30 mM), which are known to favour RuvB binding to DNA without the need for RuvA, RuvB protein alone promotes DNA unwinding. These results show that RuvB protein, an ATPase that forms hexameric ring structures that encircle the DNA, is directly responsible for the DNA unwinding activity exhibited by RuvAB. From these results, we propose that branch migration of Holliday junctions by RuvAB occurs by the passage of double-stranded DNA through the RuvAB complex, in a reaction coupled to transient DNA unwinding.

Adenosine Triphosphate↗
PubMed1992

Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation.

With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation.

Anastomosis, Surgical↗
PubMed2000

RGS molecule expression in murine B lymphocytes and ability to down-regulate chemotaxis to lymphoid chemokines.

Ag-mediated changes in B lymphocyte migration are important for normal immune function, yet the mechanisms by which these changes occur are poorly defined. Because chemokines direct many lymphocyte movements, molecules that regulate signaling by G protein-coupled chemokine receptors are likely to participate in Ag receptor-induced changes in cell migration. In this study, we have investigated the expression pattern and activity in murine B cells of members of the regulators of G protein signaling (RGS) family of molecules. We present the sequence of mouse RGS1 and describe a novel short isoform of RGS3 that we term RGS3s. Following in vivo activation by Ag, B cells rapidly up-regulate expression of RGS1 and RGS2 while simultaneously decreasing expression of RGS3 and RGS14. Anergic hen egg lysozyme autoantigen-binding B cells are also shown to have slightly elevated RGS1 and RGS2 expression. CD40 signaling, by contrast, fails to cause rapid up-regulation of RGS1 or RGS2. Using a transient transfection approach in a mature B cell line, 2PK3, we demonstrate that RGS1 and RGS3s are effective inhibitors of chemotaxis toward the lymphoid tissue chemokines stromal cell-derived factor-1, B lymphocyte chemoattractant, and EBV-induced molecule 1 ligand chemokine, whereas RGS2 has a minimal effect on migration to these chemokines. Together these findings support the conclusion that Ag-mediated changes in RGS molecule expression are part of the mechanism by which Ag receptor signaling regulates B cell migration within lymphoid tissues. The findings also suggest important roles for additional G protein-mediated events in B cell activation and tolerance.

Amino Acid Sequence↗
PubMed2005

Cutting edge: macrophage migration inhibitory factor is necessary for progression of experimental autoimmune encephalomyelitis.

Macrophage migration inhibitory factor (MIF) has been implicated in the pathogenesis of inflammatory and autoimmune diseases. The role of MIF in the progression of experimental autoimmune encephalomyelitis (EAE) was explored using MIF-/- mice. Wild-type mice showed a progressive disease course, whereas MIF-/- mice exhibited acute signs but no further progression of clinical disease. MIF-/- mice displayed markedly elevated corticosterone levels and significant decreases in the inflammatory cytokines TNF-alpha, IFN-gamma, IL-2, and IL-6 before, during, and after EAE onset. Taken together, these findings support that MIF is an important mediator of EAE progression through glucocorticoid antagonism and up-regulation of the inflammatory response.

Animals↗
PubMed2003

How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration.

The interaction of the plasma protein vitronectin with plasminogen activator inhibitor-1 (PAI-1) is central to human health. Vitronectin binding extends the lifetime of active PAI-1, which controls hemostasis by inhibiting fibrinolysis and has also been implicated in angiogenesis. The PAI-1-vitronectin binding interaction also affects cell adhesion and motility. For these reasons, elevated PAI-1 activities are associated both with coronary thrombosis and with a poor prognosis in many cancers. Here we show the crystal structure at a resolution of 2.3 A of the complex of the somatomedin B domain of vitronectin with PAI-1. The structure of the complex explains how vitronectin binds to and stabilizes the active conformation of PAI-1. It also explains the tissue effects of PAI-1, as PAI-1 competes for and sterically blocks the interaction of vitronectin with cell surface receptors and integrins. Structural understanding of the essential biological roles of the interaction between PAI-1 and vitronectin opens the prospect of specifically designed blocking agents for the prevention of thrombosis and treatment of cancer.

Amino Acid Sequence↗
PubMed2004

Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis.

We investigated the serum macrophage migration inhibitory factor (MIF) levels of palmoplantar pustulosis patients, before and after the tonsillar provocation test. Higher serum MIF levels of palmoplantar pustulosis patients were decreased after the tonsillar provocation test (n=29). To confirm these phenomena, two patients with acute tonsillitis had their changes in body temperature, C-reactive protein (CRP) and serum MIF levels examined during the course of their illness. Surprisingly, increased MIF preceded fever and CRP elevation, and MIF subsequently decreased at the onset of fever and CRP elevation. Since MIF is an initiator of other proinflammatory cytokines, we suggest that the induction of MIF may precede other inflammatory conditions.

Acute Disease↗
PubMed1996

Immunolocalization of basic fibroblast growth factor during wound repair in rat retina after laser photocoagulation.

BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key role in wound repair. We studied the immunohistochemical localization of bFGF during wound repair in the rat retina after laser photocoagulation. METHODS: Krypton laser photocoagulation was performed on the eyes of pigmented rats. The eyes were enucleated on days 1, 3, 7, 14 and 28 after the photocoagulation, and the immunohistochemical localization of bFGF was assessed. Two different monoclonal antibodies and one polyclonal antibody against bFGF as first antibodies were used. RESULTS: Marked immunoreactivity for bFGF was found in the ganglion cell layer, and weak immunoreactivity for bFGF was found in the retinal pigment epithelial (RPE) cells of the normal adult rat retina. On day 3 after laser photocoagulation, the nuclei and cytoplasm of proliferating RPE cells at the center of the photocoagulated lesion showed intense bFGF immunoreactivity. The nuclei of RPE cells around the lesion showed intense bFGF immunoreactivity. Macrophages that migrated into the lesion showed positive staining for bFGF. These immunoreactivity decreased with time. Controls (0.05 M Tris-HCl buffer, normal serum, or these same antibodies preabsorbed with bFGF) did not show positive staining. CONCLUSION: The finding of an elevated expression of bFGF immunoreactivity in the photocoagulated lesion suggests that bFGF may play a role in wound repair in the rat retina after laser photocoagulation.

Animals↗