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 1,351 records · Page 75Linked to original sources

Integrative analysis and experiment validation of SLC12A8 as a biomarker for the malignant transition from endometriosis to endometriosis associated ovarian cancer.

Endometriosis (EM) is a chronic inflammatory, estrogen‑dependent benign gynecological disorder. A subset of patients with EM may subsequently develop endometriosis‑associated ovarian cancer (EAOC), implying a biological continuum between these two conditions. Nevertheless, the molecular events underlying the progression from benign endometriotic lesions toward EAOC remain incompletely characterized. In this study, transcriptomic datasets retrieved from the GEO database were interrogated through differentially expressed gene screening, functional enrichment analysis, and weighted gene co‑expression network analysis (WGCNA) to identify key genes and pathways relevant to EM and EAOC. Candidate genes were further prioritized by integrating survival analysis via the Kaplan‑Meier Plotter, LASSO regression, random‑forest modeling, and CIBERSORT immune‑infiltration profiling. Loss and gain‑of‑function cellular models were established using siRNA and overexpression plasmids, and in‑vitro functional assays were performed to characterize the phenotypic effects of target genes.We identified several candidate genes associated with EM and EAOC and evaluated their discriminatory performance. Among them, SLC12A8 elevated expression across EM and EAOC tissues and exhibited moderate diagnostic capacity. Higher SLC12A8 expression was also associated with poorer prognosis in EAOC patients. In‑vitro experiments further demonstrated that SLC12A8 modulates proliferation, invasion, and migration in both EM and EAOC cell lines. Collectively, our exploratory research findings support SLC12A8 as a candidate functional mediator and potential biomarker linked to EM‑EAOC pathological progression, thereby extending the mechanistic understanding of these disorders.

Female↗

Role of vasopressin in the ACTH response to isoprenaline.

The present study investigated whether or not the beta-sympathomimetic amine isoprenaline, given systemically to conscious rats, influences corticotrophin (ACTH) release and if so, what could be the role of vasopressin in this response. Isoprenaline (i.m.) elevated plasma ACTH-like immunoreactivity (ACTHi) in a time- and dose-dependent manner. The highest dose of isoprenaline used (240 microgram/kg) raised plasma ACTHi about six fold. Most of the ACTHi co-migrated with porcine ACTH-(1-39) on Sephadex G-50 column chromatography. The beta-receptor antagonist propranolol abolished the increase in plasma ACTHi induced by isoprenaline, as did dexamethasone pretreatment. The increase in plasma ACTHi following isoprenaline (120 microgram/kg) injection was diminished by about 35% in rats congenitally lacking vasopressin (Brattleboro rats), when compared to normal rats. The vasopressin analogue, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]-arginine-vasopressin, almost completely prevented the rise in plasma ACTHi provoked by i.v. injection of arginine vasopressin and diminished by about 40% the isoprenaline-(120 microgram/kg)-caused ACTHi release. However, this vasopressin analogue had no effect in Brattleboro rats. These results indicate that isoprenaline, given systemically, stimulates the release of pituitary ACTH and this response appears to be mediated in part by vasopressin acting as an ACTH-releasing factor.

Adrenocorticotropic Hormone↗

The role of up-regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis.

Proteinases are important at several phases of physiological and pathological inflammation, mediating cellular infiltration, cytokine activation, tissue damage, remodeling, and repair. However, little is known of their role in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the role of tissue proteases in a mouse model of colitis. Proteolytic activity was analyzed, using gel and in situ zymography, in colonic tissues from severe combined immunodeficient mice with colitis induced by transfer of CD4(+) T lymphocytes. Serine proteinase levels increased in colitic tissue, with major species of 23 kd, 30 kd, and 45 kd. Co-migration and inhibition studies indicated that the 23-kd proteinase was pancreatic trypsin and that the 30-kd species was neutrophil elastase. Matrix metalloproteinase (MMP)-9 expression, and MMP-2 and MMP-9 activation, was elevated in colitic tissues. Proteinase levels followed a decreasing concentration gradient from proximal to distal colon. Proteolysis was localized to infiltrating leukocytes in diseased severe combined immunodeficient mice. Transmural inflammation was associated with serine proteinase and MMP activity in overlying epithelium and with marked subepithelial proteolytic activity. The results demonstrate a clear elevation in the levels and activation of proteases in colitis, potentially contributing to disease progression through loss of epithelial barrier function.

Animals↗

Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells.

Early metastasis is the primary cause of death in melanoma patients. The adhesion receptor integrin alpha v beta 3 contributes to tumor cell functions that are potentially involved in melanoma growth and metastasis. We tested whether integrin alpha v beta 3 supports metastasis of human melanoma cells when injected into the bloodstream of immune deficient mice. Comparing variants of the same melanoma cell type that expressed either alpha v beta 3, alpha IIb beta 3 or no beta 3 integrin, we found that only alpha v beta 3 strongly supported metastasis. Inhibition of tumor cell alpha v beta 3 function reduced melanoma metastasis significantly and prolonged animal survival. To understand mechanisms that allow alpha v beta 3, but not alpha IIb beta 3 to support melanoma metastasis, we analyzed proteolytic and migratory activities of the melanoma cell variants. Melanoma cells expressing alpha v beta 3, but not those expressing alpha IIb beta 3 or no beta 3 integrin, produced the active form of metalloproteinase MMP-2 and expressed elevated mRNA levels of MT1-MMP and TIMP-2. This indicates an association between alpha v beta 3 expression and protease processing. Furthermore, alpha v beta 3 expression was required for efficient melanoma cell migration toward the matrix proteins fibronectin and vitronectin. The results suggest that expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells and that the related integrin alpha IIb beta 3 cannot substitute for alpha v beta 3 in this respect.

Animals↗

Regulation of matrix metalloproteinase production by cytokines, pharmacological agents and periodontal pathogens in human periodontal ligament fibroblast cultures.

Matrix metalloproteinases (MMPs). produced by both infiltrating and resident cells of the periodontium, play a role in physiologic and pathologic events. It is recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. To date, little is known about the regulation of MMP synthesis and secretion in human periodontal ligament fibroblasts (PDLFs). The purpose of this study was to examine the effects of cytokines, pharmacological agents (protein synthesis inhibitor and protein kinase C inhibitors) and predominant periodontal pathogens (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) on MMP production in human PDLFs using gelatin zymography. The gelatin zymograms revealed that the main gelatinase secreted by human PDLFs migrated at 72 kDa and represents MMP-2. Minor gelatinolytic bands were also observed at 92 kDa regions that correspond to MMP-9. We found that A. actinomycetemcomitans, P. gingivalis and IL-1alpha can elevate MMP-2 secretion in human PDLFs. These results indicate that periodontal pathogens and inflammatory cytokines play an important role in tissue destruction and disintegration of extracellular matrix in periodontal diseases. Thus, activation of MMPs may be one of the distinct host degradative pathways in the pathogenesis of periodontitis. In addition, H7, staurosporine, cycloheximide and TGF-beta could suppress MMP-2 production. Agents that target protein synthesis or the protein kinase C pathway in human PDLFs inhibit MMP-2 production, and such inhibition may contribute to the pathogenesis of periodontal inflammation. Taken together, these findings suggest a possible new therapeutic approach, involving the use of drugs that modify host-response mechanisms to suppress or inhibit MMP-mediated tissue destruction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

A3 receptors mediate rapid inflammatory cell influx into the lungs of sensitized guinea-pigs.

BACKGROUND: Inhaled adenosine causes bronchoconstriction in asthmatics and may modulate inflammatory cell activity. Elevated adenosine levels occur in the lungs after antigen challenge of asthmatics. OBJECTIVES: The aim of this study was to investigate whether the bronchoconstrictor effects of the adenosine derivative, 5'-AMP, were associated with altered migration of inflammatory cells into the airways using a sensitized atopic guinea-pig model previously shown to display a bronchoconstrictor response. Comparisons were made with the effects of inhaled antigen. METHODS: Airway responses of conscious sensitized guinea-pigs to inhalation exposures of 5'-AMP were determined by whole body plethysmography as the change in specific airway conductance (sGaw). Influx of leucocytes into the airways was determined by bronchoalveolar lavage (BAL). RESULTS: 5'-AMP caused bronchoconstrictor airway responses in sensitized animals. Dose-dependent infiltration of inflammatory cells into the lungs occurred 1 h after 5'-AMP exposure. No bronchoconstriction or cell influx was seen in unsensitized guinea-pigs. Exposure to ovalbumin (OA) also caused influx of inflammatory cells. Twenty-four hours after an OA exposure, 5'-AMP produced no bronchoconstriction. The P1-receptor antagonists, 8-PT and 8-SPT, inhibited the 5'-AMP-induced bronchoconstriction, indicating that the bronchoconstriction seen in sensitized animals is mediated by A1 or A2 receptors. They had no effect on the cell influx, whereas the A3 antagonist, MRS-1220, significantly inhibited cellular infiltration, suggesting mediation through A3 receptors. At 24 h after an OA challenge and accompanying the cellular influx, there was airway hyper-responsiveness to the bronchoconstriction by histamine. In contrast, no hyper-responsiveness to histamine was seen 1 h after 3 mM or 24 h after 300 mM 5'-AMP. CONCLUSIONS: 5'-AMP caused a rapid migration of eosinophils and macrophages into the airways only in sensitized guinea-pigs, and this was blocked by the A3 antagonist MRS-1220. This was not associated with bronchial hyper-reactivity to histamine.

Adenosine Monophosphate↗

Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration.

P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counterreceptor that binds to P-selectin, E-selectin, and L-selectin. To determine its physiological role in cell adhesion as a mediator of leukocyte rolling and migration during inflammation, we prepared mice genetically deficient in PSGL-1 by targeted disruption of the PSGL-1 gene. The homozygous PSGL-1-deficient mouse was viable and fertile. The blood neutrophil count was modestly elevated. There was no evidence of spontaneous development of skin ulcerations or infections. Leukocyte infiltration in the chemical peritonitis model was significantly delayed. Leukocyte rolling in vivo, studied by intravital microscopy in postcapillary venules of the cremaster muscle, was markedly decreased 30 min after trauma in the PSGL-1-deficient mouse. In contrast, leukocyte rolling 2 h after tumor necrosis factor alpha stimulation was only modestly reduced, but blocking antibodies to E-selectin infused into the PSGL-1-deficient mouse almost completely eliminated leukocyte rolling. These results indicate that PSGL-1 is required for the early inflammatory responses but not for E-selectin-mediated responses. These kinetics are consistent with a model in which PSGL-1 is the predominant neutrophil P-selectin ligand but is not a required counterreceptor for E-selectin under in vivo physiological conditions.

Animals↗

Biological activity of a lipopolysaccharide extracted from Treponema hyodysenteriae.

A lipopolysaccharide (LPS) was obtained from pathogenic Treponema hyodysenteriae by hot phenol-water extraction. Various effects of the LPS on host cells were examined in vitro. Toxicity for mouse peritoneal macrophages was observed after 10 h of incubation at concentrations as low as 15 micrograms of the LPS per ml. Marked enhancement of both complement (C3) and immunoglobulin G-Fc receptor-mediated internalization was noted in macrophages obtained from mice injected 6 days previously with 75 micrograms of the material. Incorporation of [3H]thymidine into murine splenocytes was elevated approximately fourfold when splenocytes were treated with 5 to 10 micrograms of LPS per ml. Incubation of the LPS with normal porcine serum resulted in the generation of a factor(s) that stimulated the migration of porcine leukocytes. Generation of the chemotactic activity was inhibited by heating the serum at 56 degrees C for 30 min before treatment with LPS. The results suggest that T. hyodysenteriae contains an LPS that is biologically active.

Animals↗

Genetic and biochemical analysis of mutacin 1140, a lantibiotic from Streptococcus mutans.

Streptococcus mutans JH1000 and its derivatives were previously shown (J. D. Hillman, K. P. Johnson, and B. I. Yaphe, Infect. Immun. 44:141-144, 1984) to produce a low-molecular-weight, broad-spectrum bacteriocin-like inhibitory substance (BLIS). The thermosensitive vector pTV1-OK harboring Tn917 was used to isolate a BLIS-deficient mutant, DM25, and the mutated gene was recovered by shotgun cloning in Escherichia coli. Sequence analysis of insert DNA adjacent to Tn917 led to the identification of four open reading frames including two (lanA and lanB) which have substantial homology to the Staphylococcus epidermidis structural gene (epiA) and a modifying enzyme gene (epiB) for biosynthesis of the lantibiotic epidermin, respectively. Although the BLIS activity could not be recovered from broth cultures, high yields were obtained from a solid medium consisting of Todd-Hewitt broth containing 0.5% agarose that was stab inoculated with JH1140 (a spontaneous mutant of JH1000 that produces threefold-elevated amounts of activity). Agar could not substitute for agarose. Chloroform extraction of the spent medium produced a fraction which yielded two major bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The faster-migrating band was absent in chloroform extracts of the mutant, DM25. The amino acid sequence of this band was determined by Edman sequencing and mass spectroscopy. The results showed that it is a lantibiotic, which we have named mutacin 1140, and that the sequence corresponded to that deduced from the lanA sequence. We observed a number of similarities of mutacin 1140 to epidermin and an S. mutans lantibiotic, B-Ny266, but it appears to have significant differences in the positions of its thioether bridges. It also has other unique features with regard to its leader sequence and posttranslational modification. A proposed structure for mutacin 1140 is presented.

Amino Acid Sequence↗

Enhanced RASGEF1A expression is involved in the growth and migration of intrahepatic cholangiocarcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: To identify novel molecular targets for the treatment of intrahepatic cholangiocarcinoma (ICC), the second most common type of primary hepatobiliary cancer, we earlier analyzed genome-wide expression profiles of genes in 25 ICCs. Among the genes whose expression levels were commonly elevated in the tumors, we identified a novel gene termed RASGEF1A that encodes a putative Ras guanine nucleotide exchange factor domain-containing protein. RESULTS: We showed in this article that RASGEF1A protein has a guanine nucleotide exchange activity to K-RAS, H-RAS, and N-RAS proteins in vitro. Consistently, exogenous RASGEF1A expression increased the activity of Ras. In addition, suppression of RASGEF1A by small interfering RNA retarded the growth of cholangiocarcinoma cells. Interestingly, COS7 cells expressing exogenous RASGEF1A showed enhanced cellular motility in Transwell and wound-healing assays. CONCLUSIONS: These data suggest that elevated expression of RASGEF1A may play an essential role for proliferation and progression of ICC. Our data indicate that RASGEF1A may be a promising therapeutic target for the majority of ICCs.

Animals↗

Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene.

Although prostate-restricted replicative adenovirus has exhibited significant antitumor efficacy in preclinical studies, it is necessary to develop more potent adenoviruses for prostate cancer gene therapy. We evaluated the synergistic killing effect of prostate-restricted replicative adenovirus and AdEndoAngio, a replication-defective adenovirus expressing the endostatin-angiostatin fusion protein (EndoAngio). When coadministered with AdEndoAngio, prostate-restricted replicative adenovirus significantly elevated EndoAngio expression, suggesting that AdEndoAngio coreplicates with prostate-restricted replicative adenovirus. Conditioned medium from prostate cancer cells infected by prostate-restricted replicative adenovirus plus AdEndoAngio inhibited the growth, tubular network formation, and migration of human umbilical vein endothelial cells better than conditioned medium from prostate cancer cells infected by AdEndoAngio alone. Furthermore, in vivo animal studies showed that the coadministration of prostate-restricted replicative adenovirus plus AdEndoAngio resulted in the complete regression of seven out of eight treated androgen-independent CWR22rv tumors, with a tumor nodule maintaining a small size for 14 weeks. The residual single tumor exhibited extreme pathologic features together with more endostatin-reactive antibody-labeled tumor cells and fewer CD31-reactive antibody-labeled capillaries than the AdEndoAngio-treated tumors. These results show that combination therapy using prostate-restricted replicative adenovirus together with antiangiogenic therapy has more potent antitumor effects and advantages than single prostate-restricted replicative adenovirus and deserves more extensive investigation.

Adenoviridae↗

Eosinophil-associated inflammation and elaboration of eosinophil-derived proteins in 2 children with raccoon roundworm (Baylisascaris procyonis) encephalitis.

OBJECTIVE: Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection. METHODS: Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophil-derived neurotoxin and major basic protein, were assayed in the CSF. RESULTS: Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophil-derived neurotoxin, and major basic protein were markedly elevated over controls. CONCLUSIONS: This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.

Animals↗

Function of peritoneal exudate cells after abdominal surgery.

Peritoneal macrophages and polymorphonuclear neutrophils are key cells in the repair of postoperative injury. Increased numbers of macrophages migrate into the peritoneal cavity after operation and the function of these cells changes over the postoperative interval. Macrophage activities, such as respiratory burst, arachidonic acid metabolism, monokine secretion, and plasminogen activator inhibitory activity, are elevated by peritoneal operation. However, the secretion of plasminogen activator activity is decreased after operation. The kinetics with which each of these functions changes varies with the parameter examined, indicating a complex regulation of the differentiation of leukocytes after operation. In addition, the activity of postoperative macrophages can be modulated in vitro by exposure to cytokines and conditioned media from polymorphonuclear neutrophils and macrophages. Thus, cell-cell interactions and factors secreted within the peritoneal cavity may regulate the contribution of postoperative leukocytes to peritoneal repair after operation.

Abdomen↗

HIV type 1 Nef protein is a viral factor for leukocyte recruitment into the central nervous system.

Recombinant HIV-1 Nef protein, but not Tat, gp120, and gp160, provoked leukocyte recruitment into the CNS in a rat model. The strong reduction of bioactivity by heat treatment of Nef, and the blocking effect of the mAb 2H12, which recognizes the carboxy-terminal amino acid (aa) residues 171-190 (but not of mAb 3E6, an anti-Nef Ab of the same isotype, which maps the aa sequence 168-175, as well as a mixture of mAbs to CD4) provided evidence for the specificity of the observed Nef effects. Using a modified Boyden chamber technique, Nef exhibited chemotactic activity on mononuclear cells in vitro. Coadministration of the anti-Nef mAb 2H12, as well as treatment of Nef by heat inhibited Nef-induced chemotaxis. Besides soluble Nef, chemotaxis was also induced by a Nef-expressing human astrocytoma cell line, but not by control cells. These data suggest a direct chemotactic activity of soluble Nef. The detection of elevated levels of IL-6, TNF-alpha, and IFN-gamma in rat cerebrospinal fluid 6 h after intracisternal Nef injection hint at the additional involvement of indirect mechanisms in Nef-induced leukocyte migration into rat CNS. These data propose a mechanism by which HIV-1 Nef protein may be essential for AIDS neuropathogenesis, as a mediator of the recruitment of leukocytes that may serve as vehicles of the virus and perpetrators for disease through their production of neurotoxins.

Animals↗

Characterization of lymphocyte surface markers in patients with vitiligo.

It was demonstrated that all vitiligo patients, independently of the disease stage, have a significant decrease in the total number of T cells and an elevated level of peripheral blood lymphocytes and activated natural killers (CD56). The low level of T lymphocytes is associated with the increase in the number of CD3(+)4(+)8(+) cells, which are characterized by a faster apoptosis induction. The elevated level of B lymphocytes in peripheral blood in vitiligo is due to the significant increase in the number of B cells of all the stages of differentiation, suggesting a general activation of the whole B-cell immunity. Perhaps, it is associated with the continuous stimulations of B cells by the type 2 helper lymphocytes. The Th2 lymphocyte mediators, including IL-4, do not only stimulate of B-cell immunity, but also regulate maturation of NK cells. It is typical for vitiligo that the level of mature B cells responsible for Ig synthesis (CD38(+), mIgM(+), mIgG(+)) stays elevated even in remission. Moreover, a considerable increase in the number of peripheral blood lymphocytes expressing the adhesion receptor CD54 is observed, which most likely reflects that the blood lymphocytes are highly prepared for tissue migration.

B-Lymphocytes↗

Granulocyte-macrophage colony-stimulating factor induces neutrophil adhesion to pulmonary vascular endothelium in vivo: role of beta 2 integrins.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) causes upregulation of neutrophil surface CD11b/CD18 expression, and enhances the adhesion of neutrophils to cultured human endothelial cells in vitro. Systemic administration of GM-CSF results in a rapid, transient decrease in circulating phagocyte numbers. Using a nonhuman primate model (Cynomolgus), we provide histologic evidence that this transient leukopenia is associated with the margination of neutrophils in the pulmonary microcirculation. In four animals receiving 2 to 15 micrograms/kg recombinant human GM-CSF (rhGM-CSF), light microscopic sections of lung contained 36 +/- 8, 17 +/- 7, 21 +/- 6, and 15 +/- 8 (mean +/- SD, n = 20) neutrophils within a graticule grid, as compared with two control animals receiving saline injections whose lung sections contained 2.1 +/- 1.6 and 3.1 +/- 2.1 (mean +/- SD, n = 20) neutrophils within the same grid. Scanning electron microscopy shows activated leukocytes adherent to pulmonary vascular endothelium, but no morphologic evidence of endothelial damage, and no migration of cells into the extravascular space. Margination is associated with an increase in surface expression of CD11b/CD18 on circulating phagocytes, which could contribute to the adhesion to capillary endothelial cells, but CD11b/CD18 levels remain elevated even when demargination is complete. In vitro, monoclonal antibodies (MoAbs) to CD18 and CD11b were able to inhibit neutrophil aggregation and adhesion to endothelium. FMLP-induced neutrophil aggregation was inhibited by 39.8% +/- 11.5% and 44.8% +/- 12.3%, respectively, by MoAbs to CD18 and CD11b (P less than .0005, n = 4 for both); a similar effect was demonstrated on TPA-induced aggregation. MoAb CD18 reduced the adhesion of unstimulated neutrophils to endothelium by 44% (P less than .01, n = 7), and inhibited the amount of GM-CSF-stimulated adhesion by 74% (P less than .001, n = 7), while MoAb to CD11b produced a reduction of unstimulated neutrophil adhesion by 30%, and of GM-CSF-stimulated adhesion by 40% (P less than .01, n = 5, for both). However, when administered in vivo, MoAb CD18 produced only a small, albeit significant, amelioration of GM-CSF-induced margination in vivo, while MoAb CD11b was without effect. These results show that GM-CSF-induced transient leukopenia is associated with enhanced neutrophil adherence to pulmonary vascular endothelium, but suggest that the beta 2 leukocyte integrins CD11/CD18 play only a minor role in this process.

Antibodies, Monoclonal↗

Synthetic urokinase inhibitors as potential anti-invasive drugs.

In carcinogenesis, proteinases play an important role in metastasis of solid malignant tumors. Aside from several matrix metalloproteinases and cathepsins, the urokinase-plasmin system seems to be one of the main players within the cell surface-associated proteolytic activity, facilitating tumor cell migration and invasion. Upon binding to a specific receptor, the enzymatic activity of urokinase is focused to the cell surface. The significance of the plasminogen activator system in malignancy is underlined by the finding of elevated levels of urokinase and its receptor in tumor tissues. Therefore, the possible use of urokinase inhibitors in the therapeutic treatment of cancer and metastasis has been the subject of intensive investigations. This review covers synthetic inhibitors of urokinase described up to December 2000, although the number of lead structures is still relatively small.

Journal Article↗

Human granulocyte function during dextran infusion.

The granulocyte function was determined in healthy persons before and immediately after the infusion of 500 ml of dextran for 4 hours. The nitroblue tetrazolium (NBT) reduction reflecting the metabolic activity of these cells was measured both in cells at rest and after stimulation with E. coli, as well as with and without the addition of plasma. In 13 persons, the NBT-reduction was slightly but significantly increased in all four types of experiments after the dextran infusion. When dextran was added in vitro to granulocytes from normal volunteers, the NBT reduction of these cells was increased and the effect was dose-dependent. A surface effect of dextran together with phagocytosis of dextran molecules are the most probable reasons for the elevated NBT-reduction. - In 9 persons tested, the bactericidal capacity was not significantly influenced by dextran infusion. - When dextran was added in vitro to granulocytes neither the bactericidal capacity nor the chemotactic and random migration of the cells were changed. -

Adult↗