Does Cytomegalovirus Play a Role in Atherosclerosis?

In vitro experiments, as well as experiments using animal models, suggest that cytomegalovirus (CMV) infection can stimulate atherosclerosis. There is also evidence that CMV stimulates the development of restenosis and transplantation-associated arteriosclerosis. Activation of arterial cells, enhancement of the inflammatory response and induction of cytokine production may all be important in mediating these effects. Further experiments, especially in animals susceptible to atherosclerosis and in patients with cardiovascular disease, will be necessary to elucidate the role of CMV, and also that of other infectious agents, in atherosclerosis.     

Do Regulatory T Cells Play a Role in the Control of Homeostatic Proliferation?

The control of peripheral lymphocyte numbers is a fundamental aspect of the immune system. Regulatory T cells are involved in the suppression of autoimmune, antitumor, allergic, and other inflammatory responses, as well as in facilitating graft acceptance. In this paper, we discuss whether the control of homeostatic proliferation is another facet of the immune system that is controlled by regulatory T cells. A review of the published data connecting regulatory T cells with the control of homeostatic proliferation indicates that several key questions remain open. One of these relates to the stage at which regulatory T cells could play a role (i.e., T-cell proliferation vs. survival).     

MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart: Do They Play a Role in Cardiac Hypertrophy?

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin II or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.     

MicroRNA: Could It Play a Role in Bovine Endometritis?

Inflammation - Endometritis in dairy cows is a major economic problem worldwide; without advances in lifestyle management and drug treatment, it causes high morbidity and death. Micro ribonucleic...     

N-Cadherin-Mediated Human Granulosa Cell Adhesion Prevents Apoptosis : A Role in Follicular Atresia and Luteolysis?

Studies suggest that cell-cell interactions may regulate apoptosis, and in particular, the calcium-dependent cell adhesion molecule N-cadherin has been shown to be capable of modulating this process. Rat granulosa cells (GCs) are known to express N-cadherin whereas cAMP is known to induce apoptosis in human and rat GCs. Based on these observations, we hypothesized that N-cadherin regulates human GC apoptosis via a cAMP-dependent mechanism. N-cadherin expression was evaluated in ovarian follicles and corpora lutea utilizing immunohistochemical techniques and in luteinized GCs in culture using immunoblotting, flow cytometric analysis, immunohistochemistry, and indirect immunofluorescence techniques utilizing anti-N-cadherin antibodies directed against both the extracellular and cytoplasmic domains of the molecule. Apoptosis was assessed by TUNEL and DNA fragmentation analysis and confirmed by flow cytometric cell cycle analysis and electron microscopy. The rate of GC apoptosis was found to be two- to three-fold lower among aggregated cells, as compared with single cells. N-cadherin was found to be expressed by aggregating GCs in vitro and GCs cultured in the presence of either N-cadherin function disrupting antibodies or peptides exhibiting enhanced rates of apoptosis. GCs in situ stained intensely for N-cadherin in preantral and normal growing preovulatory follicles as well as early corpora lutea. N-cadherin was weak in atretic follicles and regressing corpora lutea. Exposure of GCs to cAMP increased apoptosis while decreasing N-cadherin protein expression in a dose-dependent manner. Cell culture under serum-free conditions increased apoptosis and decreased N-cadherin expression, in part through cleavage of the extracellular domain of the molecule. The metalloproteinase inhibitor 1-10-phenanthroline inhibited the cleavage of the extracellular domain of N-cadherin and concomitantly inhibited the serum-deprivation-induced apoptosis of aggregated GCs. Collectively, these observations suggest that down-regulation of N-cadherin or the absence of a functional extracellular domain of the molecule prevents cell aggregation and is associated with GC apoptosis. In addition, cAMP induces apoptosis in a dose-dependent manner, and this process is dependent, at least in part, on regulation of the N-cadherin molecule at the surface of the cells. We conclude that N-cadherin-mediated GC signaling plays a central role in follicular and luteal cell survival.     

Appearance of Tissue Transglutaminase in Astrocytes in Multiple Sclerosis Lesions: A Role in Cell Adhesion and Migration?

Multiple Sclerosis (MS) is a neuroinflammatory disease mainly affecting young adults. A major pathological hallmark of MS is the presence of demyelinated lesions in the central nervous system. In the active phase of the disease, astrocytes become activated, migrate and contribute to local tissue remodeling that ultimately can result in an astroglial scar. This process is facilitated by extracellular matrix proteins, including fibronectin. Tissue Transglutaminase (TG2) is a multifunctional enzyme with a ubiquitous tissue distribution and it has been shown that inflammatory cytokines can induce TG2 activity. In addition, TG2 is known to mediate cell adhesion and migration. We therefore hypothesized that TG2 is present in MS lesions and plays a role in cell adhesion and/or migration. Our studies showed that TG2 immunoreactivity appeared in astrocytes in active and chronic active MS lesions. These TG2 positive astrocytes partly co‐localized with fibronectin. Additional in vitro studies showed that TG2 mediated astrocytoma adhesion to and migration on the extracellular matrix protein fibronectin. We therefore speculate that TG2 mediates the enhanced interaction of astrocytes with fibronectin in the extracellular matrix of MS lesions, thereby contributing to astrocyte adhesion and migration, and thus in tissue remodeling and possibly glial scarring.     

Does Thrombin Play a Role in the Pathogenesis of Brain Damage After Periventricular Hemorrhage?

Neonatal periventricular hemorrhage (PVH) is a devastating complication of prematurity in the human infant. Based upon observations made primarily in adult rodents and the fact that the immature brain uses proteolytic systems for cell migration and growth, we hypothesized that thrombin and plasmin enzyme activities contribute to the brain damage after PVH. The viability of mixed brain cells derived from newborn rat periventricular region was suppressed by whole blood and thrombin, but not plasmin. Following injection of autologous blood into the periventricular region of newborn rat brain, proteolytic activity was detected in a halo around the hematoma using membrane overlays impregnated with thrombin and plasmin fluorogenic substrates. Two-day old rats received periventricular injection of blood, thrombin, and plasminogen. After 2 days, thrombin and blood were associated with significantly greater damage than saline or plasminogen. Two-day old mice received intracerebral injections of blood in combination with saline or the proteolytic inhibitors hirudin, alpha2macroglobulin, or plasminogen activator inhibitor-1. After 2 days, hirudin significantly reduced brain cell death and inflammation. Two-day-old mice then received low and high doses of hirudin mixed with blood after which behavioral testing was conducted repeatedly. At 10 weeks there was no statistically significant evidence for behavioral or structural brain protection. These results indicate that thrombin likely plays a role in neonatal periventricular brain damage following PVH. However, additional factors are likely important in the recovery from this result.     

Can the First Addition of Alkyl Radicals Play a Role in the Fate of NMP?

Values of k_d for the C? ON bond homolysis were measured for alkoxyamines based on imidazoline and imidazole nitroxides. They were analyzed in terms of polar/stabilization, steric, and entropic effects. k_d decreased with increasing electron‐withdrawing capacities of the groups attached to the nitroxide, but increasing with both the bulkiness of the group attached to the nitroxide and the presence of substituents on the ring. With three alkoxyamines, it was shown that the fate of the NMP of styrene depended on the type of initiating alkyl radical: successful for initiating 1‐phenylethyl radicals and unsuccessful for initiating p‐nitrophenyloxycarbonyl‐2‐prop‐2‐yl radicals.

     

Does Hemopoietic Stem Cell Transplantation Have a Role in Treatment of Severe Rheumatoid Arthritis?

Based on animal models and limited clinical experience, there is considerable interest in use of high-dose immunosuppression followed by hemopoietic stem cell transplantation as treatment for severe rheumatoid arthritis. Because of its relatively low treatment-related mortality and morbidity, autologous transplantation is a more attractive option than allogeneic transplantation for initial clinical trials, even though anecdotal reports suggest that allogeneic transplantation has a greater likelihood of bringing about long-term disease control. The approach remains experimental with many unanswered questions such as the value and safety of high-dose therapy without transplantation, the need for T cell purging, the possible deleterious effects of post-transplant hemopoietic growth factors and the potential of mini allogeneic transplantation (a process whereby intense immunosuppression is combined with less intense myelosuppression). To achieve quick progress it is essential that clinical trials be carefully designed with all cases being reported to the Autoimmune Disease Stem Cell Project Database.     

Do Fish Thrombocytes Play an Immunological Role? Their Cytoenzymatic Profiles and Function During an Accidental Piscine Candidiasis in Aquarium

Fish (F) thrombocytes (THRs) from healthy trouts were studied in terms of cytoenzyme expression. FTHRs were positive to acid periodic of shiff (PAS) and acid phosphatase (ac. phos.) without tartaric acid (? TA) stainings, as well to alkaline phosphatase. However, when compared with autologous macrophages (MØs), they were negative to naphthol cloroacetate esterase (AS-D), α-naphthyl acetate esterase (Anae), peroxidase (perox) and control ac. phos. with tartaric acid (+ TA) stainings, thus indicating a lack of typical lysosomial enzymes. This evidence supports the notion that FTHRs are not true digesting cells. Quite interestingly, trouts and human MØs were positive for PAS, AS-D, Anae, and perox stainings, thus confirming that cellular cytochemistries are maintained across evolution as their phagocytic functions. Additionally, blood films from trouts, accidentally infected with Candida albicans in aquarium, were morphologically analyzed. Actually, FTHRs interact with erythrocytes, potentiating the formation of rosettes around a central MØ. Polymorph nuclear cells and lymphocytes are present in these cellular aggregates, thus suggesting that FTHRs may represent a link between innate and adaptive immunity.     

Success in Weight Management Among Patients with Type 2 Diabetes: Do Perceived Autonomy Support,Autonomous Motivation,and Self-Care Competence Play a Role?

Based on self-determination theory (SDT), this study investigated whether the three central SDT variables—perceived autonomy support (from a physician), autonomous motivation and self-care competence—were associated with success in weight management (SWM) among primary care patients with type 2 diabetes when the effect of other important life-context factors was controlled for. Patients participated in a mail survey in 2011. Those who had tried to change their health behavior during the past two years in order to lose weight, either with or without success (n = 1433, mean age 63 years, 50% men), were included in this study. The successors were more autonomously motivated and energetic than the non-successors. Moreover, male gender, younger age, taking oral medication only, and receiving less social support in diabetes care predicted better success. Autonomous motivation predicted SWM; self-care competence also played a role by partly mediating the effect of autonomous motivation on SWM. These results support the idea of SDT that internalizing the value of weight management and its health benefits is necessary for long-term maintenance of health behavior change. Perceived autonomy support was not directly associated with SWM. However, physicians can promote patients' weight management by supporting their autonomous motivation and self-care competence.     

Soluble Hla Class I Antigens in Chronic Hepatitis C: A Disease-Associated Manifestan or Molecules Modulating Immunoresponsiveness?

Abstract

The occurrence of high levels of soluble human leukocyte class I antigens (sHLA-I) represents an usual finding during the course of different clinical conditions, such as viral infections and autoimmune disorders. On the other hand, the well known property of sHLA-I to modulate T cell responsiveness could be taken as an advantage to improve long-term allograft acceptance.

Recent data have pointed out that subjects with chronic hepatitis C virus (HCV) infection exhibit high amounts of sHLA-I, a pattern which has also been used for monitoring host responsiveness to interferon α (IFN-α) therapy. However, the lack of correlation between lymphocyte infiltration at liver site and disease biological activity suggests a potential role for sHLA-I in T cell dysfunction during chronic hepatitis C. sHLA-I antigens may, in fact, either interact with T cell receptor delivering an inhibitory signal or trigger cytotoxic T lymphocyte apoptosis by inducing CD95 ligand expression. Both events seem to favour HCV replication and liver tissue damage progression.

Altogether, these findings indicate that, besides viral variant generation and HCV core-mediated immunosuppression, sHLA-I may contribute to the imbalance of immunoresponsiveness during chronic HCV infection.     

Stress--Where are we Now? Does Immunity Play an Intrinsic Role?

The whole world experiences progress and development, however it is the human being who pays the price in stress--an inevitable part of modern life. When encountering stress, an individual reacts at the level of both the micro- and macroenvironment. Nowadays, stress is defined as a real or interpreted threat to the physiological or psychological integrity of an individual, which results in a physiological and/or behavioral response. In the article a review of the stress conceptualization, health consequences of stress (its neuro- physiology and relation to autoimmune disease) as well as ways of management (exercises and psychotherapeutic intervention) is given.     

From Soluble Aβ to Progressive Aβ Aggregation: Could Prion‐Like Templated Misfolding Play a Role?

Accumulation, aggregation and deposition of Aβ peptides are pathological hallmarks in the brains of individuals affected by Alzheimer's disease (AD) or by cerebral β‐amyloid angiopathy (Aβ‐CAA). While Aβ is a peptide of yet largely unknown function, it is constantly produced in the human brain where it normally remains in a soluble state. However, Aβ peptides are aggregation prone by their intrinsic ability to adopt alternative conformations rich in β‐sheet structure that aggregate into oligomeric as well as fibrillar formations. This transition from soluble to aggregated state has been hypothesized to initiate the pathological cascade and is therefore subject to intensive research. Mounting evidence suggests prion‐like templated misfolding as the biochemical phenomenon responsible for promoting progressive Aβ aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral Aβ aggregation may indeed progress via prion‐like templated misfolding. The implications of these findings are discussed with respect to understanding initiation and progression of the disease and to developing therapeutics.