Method of treating endothelial dysfunction comprising administration of a thrombin peptide derivative

Endothelial dysfunction (ED) is associated with a number of diseases and disorders. Agonists of the non-proteolytically activated thrombin receptor can be used in methods to treat ED or ED-related diseases and disorders.Board of Regents, University of Texas Syste

Adjustable single incision sling Ajust — the effects of first operations controlled by pelvic floor sonography

Objective: The aim of this study is to evaluate using PFS-TV the mid-term results of our first operative experience with implanting a single incision sling — Ajust™. Material and methods: One and the same surgeon has operated all the patients with symptoms of stress urinary incontinence. Ajust was the only performed procedure. Postoperative evaluation consisted of: a standardized interview and examination, a cough test and a PFS-TV for evaluation of urinary continence and tape location. PFS-TV was performed under standardized conditions at rest and during maximum Valsalva maneuver. Results: This is a retrospective analysis of data from a total of 31 patients who attended a control visit between the 36th and the 50th month following the operation. Sixteen patients (51.6%) were cured. There were statistically significant differences in urethral mobility (p < 0.0007) and tape-urethra distance (p < 0.002) between cured and not-cured group. The difference in urethral length was not statistically significant. 77.8% of women with a hypermobile urethra was cured in contrast to 15.4% with a normobile urethra. Neither of the groups had a hypomobile urethra patient. There were no significant complications intra- or post-operatively. De novo urgency was observed in 1 patient only. Conclusions: Implantation of Ajust tape seems to be a safe mode of operative treatment for SUI in women. Our mid-term results suggest that long term effects might be worse compared to retropubic or transobturator tapes, especially at first operative experience with Ajust. Urethral mobility seems to be an important risk factor for treatment failure after Ajust implantation. It seems that patients that may benefit from Ajust most are women with urethral hypomobility but this needs to be verified with a prospective study

Differential Expression of Ovine Innate Immune Genes by Preterm and Neonatal Lung Epithelia Infected with Respiratory Syncytial Virus

Preterm infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. The cause(s) for this age-dependent vulnerability is/are not well-defined, but alterations in innate immune products have been implicated. In sheep, RSV disease severity has similar age-dependent characteristics and sheep have several related innate molecules for study during pulmonary infection including surfactant protein A (SP-A), surfactant protein D (SP-D), sheep beta defensin 1 (SBD1), monocyte chemotactic protein 1 (MCP1), and Toll-like receptor 4 (TLR4). However, the in vivo cellular gene expression as a response to RSV infection is poorly understood. In this study, the effect of RSV infection on expression of these innate immune genes was determined for bovine RSV-infected (bRSV+ fluorescence) epithelial cells, adjacent cells lacking bRSV antigen (adjoining cells lacking fluorescence), and control cells from non-infected lung using laser capture microdissection (LCM) and real-time RT-PCR. Control lambs had increased expression of innate immune molecules in full term (term) compared to preterm epithelia with statistical significance in SBD1, SP-D, and TLR4 mRNA. Infected cells (bRSV+ fluorescent cells) had consistently higher mRNA levels of SP-A (preterm and term), MCP1 (preterm and term), and SP-D (preterm). Interestingly, bRSV- cells of infected term lambs had significantly reduced SP-D mRNA expression compared to bRSV+ and control epithelia, suggesting that RSV infected cells may regulate the adjacent epithelial SP-D expression. This study defines specific innate immune components (e.g., SBD1, SP-D, and TLR4) that have differential age-dependent expression in the airway epithelia. Furthermore, cellular bRSV infection enhanced certain innate immune components while suppressing adjacent cellular SP-D expression in term animals. These in vivo gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis

Eosinophil Cationic Protein and Chemokines in Nasopharyngeal Secretions of Infants with Respiratory Syncytial Virus (RSV) Bronchiolitis and Non-RSV Bronchiolitis

Bronchiolitis is a risk factor for the development of childhood asthma. Eosinophilic inflammation in airways plays an important role in the pathophysiology of both bronchiolitis and asthma. To investigate this inflammation, we measured the eosinophil cationic protein (ECP), regulated on activation normal T-cell expressed and secreted (RANTES) and eotaxin levels in nasopharyngeal secretions (NPS). Twenty-eight patients with RSV bronchiolitis (RSV group), 11 patients with non-RSV bronchiolitis (non-RSV group) and 7 controls were enrolled in this study. ECP, RANTES, and eotaxin levels were measured by enzyme immunoassays. The ECP level in the NPS of the RSV group was significantly higher than that in the NPS of the non-RSV group and controls. RANTES and eotaxin levels in infants with bronchiolitis were significantly higher than those in the controls, but there was no significant difference between the RSV and non-RSV groups. In conclusion, with regard to eosinophilic airway inflammation, as compared with non-RSV bronchiolitis, RSV bronchiolitis may be more similar to childhood asthma

Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle

Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1-dependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src inactivation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers

Eosinophil Survival and Apoptosis in Health and Disease

Eosinophilia is common feature of many disorders, including allergic diseases. There are many factors that influence the production, migration, survival and death of the eosinophil. Apoptosis is the most common form of physiological cell death and a necessary process to maintain but limit cell numbers in humans and other species. It has been directly demonstrated that eosinophil apoptosis is delayed in allergic inflammatory sites, and that this mechanism contributes to the expansion of eosinophil numbers within tissues. Among the proteins known to influence hematopoiesis and survival, expression of the cytokine interleukin-5 appears to be uniquely important and specific for eosinophils. In contrast, eosinophil death can result from withdrawal of survival factors, but also by activation of pro-apoptotic pathways via death factors. Recent observations suggest a role for cell surface death receptors and mitochondria in facilitating eosinophil apoptosis, although the mechanisms that trigger each of these death pathways remain incompletely delineated. Ultimately, the control of eosinophil apoptosis may someday become another therapeutic strategy for treating allergic diseases and other eosinophil-associated disorders

Respiratory syncytial virus infection induces higher Toll-like receptor-3 expression and TNF-α production than human metapneumovirus infection

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Induction of reactive oxygen intermediates in human monocytes by tumour cells and their role in spontaneous monocyte cytotoxicity

The present study examined the ability of human monocytes to produce reactive oxygen intermediates after a contact with tumour cells. Monocytes generated oxygen radicals, as measured by luminol-enhanced chemiluminescence and superoxide anion production, after stimulation with the tumour, but not with untransformed, cells. The use of specific oxygen radical scavengers and inhibitors, superoxide dismutase, catalase, dimethyl sulphoxide and deferoxamine as well as the myeloperoxidase inhibitor 4-aminobenzoic acid hydrazide, indicated that chemiluminescence was dependent on the production of superoxide anion and hydroxyl radical and the presence of myeloperoxidase. The tumour cell-induced chemiluminescent response of monocytes showed different kinetics from that seen after activation of monocytes with phorbol ester. These results indicate that human monocytes can be directly stimulated by tumour cells for reactive oxygen intermediate production. Spontaneous monocyte-mediated cytotoxicity towards cancer cells was inhibited by superoxide dismutase, catalase, deferoxamine and hydrazide, implicating the role of superoxide anion, hydrogen peroxide, hydroxyl radical and hypohalite. We wish to suggest that so-called ‘spontaneous’ tumoricidal capacity of freshly isolated human monocytes may in fact be an inducible event associated with generation of reactive oxygen intermediates and perhaps other toxic mediators, resulting from a contact of monocytes with tumour cells. © 1999 Cancer Research Campaig