The integrative roles of chemokines at the maternal-feta interface in early pregnancy

Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.     

转化生长因子-β在哮喘气道炎症与重塑中的作用

Transforming growth factor-β(TGF-β) was reported to be increased in asthma in some studies. Accumulation of TGF-β in airway promotes smooth muscle cell mitogenesis and hyperplasia, and in-duces fibroblast and myofibroblast and smooth muscle proliferation as well as increase in protein synthesis in connective tissue(such as collagen deposition on the reticular basement membrane). The autocrine induction of collagen expression by smooth muscle may contribute to the thickening of the reticular basement membrane, irre-versible f‘throsis and remodeling seen in the airways in some asthmatics. TGF-β is considered to be a major fi-brogenic cytokine. It can increase smooth muscle mass and lead to severe bronchial obstruction in an asthma at-tack.     

Current perspectives of nanoparticles in medical and dental biomaterials

Nanotechnology is gaining tremendous impetus due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Nanoparticles have been introduced as materials with good potential to be extensively used in biological and medical applications. Nanoparticles are clusters of atoms in the size range of 1-100 nm. Inorganic nanoparticles and their nano-composites are applied as good antibacterial agents. Due to the outbreak of infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance, pharmaceutical companies and researchers are searching for new antibacterial agents. The metallic nanoparticles are the most promising as they show good antibacterial properties due to their large surface area to volume ratios, which draw growing interest from researchers due to increasing microbial resistance against metal ions, antibiotics and the development of resistant strains. Metallic nanoparticles can be used as effective growth inhibitors in various microorganisms and thereby are applicable to diverse medical devices. Nanotechnology discloses the use of elemental nanoparticles as active antibacterial ingredient for dental materials. In dentistry, both restorative materials and oral bacteria are believed to be responsible for restoration failure. Secondary caries is found to be the main reason to restoration failure. Secondary caries is primarily caused by invasion of plaque bacteria (acid-producing bacteria) such as Streptococcus mutans and lactobacilli in the presence of fermentable carbohydrates. To make long-lasting restorations, antibacterial materials should be made. The potential of nanoparticles to control the formation of biofilms within the oral cavity is also coming under in- creasing scrutiny. Possible uses of nanoparticles as topically applied agents within dental materials and the appli- cation of nanoparticles in the control of oral infections are also reviewed.     

Salmonella Typhi： from a Human Pathogen to a Vaccine Vector

Salmonella （S.） typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular ＆ Molecular Immunology.     

MicroRNA在脑胶质瘤中的作用

icroRNAs (miRNAs) are critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than one third of protein-coding genes, and have been implicated in the control of many biological processes, including the biology of glioma. The functional significance in some of the miRNAs begins to emerge. This paper reviews the biogenesis of miRNAs, their roles in neuronal development and tumorigenesis of gliomas, and their contribution as tumor biomarkers. Research in this area is quickly gathering pace and is illuminating important aspects of the diseases that may ultimately lead to novel therapeutic interventions, as well as diagnostic and prognostic tools for brain tumors.     

CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40-induced RAG expression

CD4＋ T cells expressing CD40 （Th40 cells） constitute a pathogenic T-cell subset that is necessary and sufficient to transfer autoimmune disease. We have previously demonstrated that CD40 signals peripheral Th40 cells to induce RAG1 and RAG2 expression, proteins necessary for the expression of T-cell receptor （TCR）, leading to TCR revision. The dependency of TCR expression in the thymus on RAG proteins has long been known. However, despite numerous publications, there is controversy as to whether TCR expression can be altered in the periphery, post-thymic selective pressures. Therefore, a better understanding of TCR expression in primary peripheral cells is needed. We now show that the CD40 protein itself interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus in Th40 cells. This indicates that the CD40 molecule is closely involved in the mechanism of TCR expression in the periphery. In addition, Fas signals act as a silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the nucleus. It will be important to further understand the involvement of CD40 in peripheral TCR expression and how TCR revision impacts auto-antigen recognition in order to effectively target and tolerize autoaggressive T cells in autoimmune disease.     

Immunological effects of silica and asbestos

Silicosis patients （SILs） and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis （known as Caplan syndrome）, and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cellmediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestosrelated malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.     

A STUDY OF THE NERVE FIBERS ORIGINATED FROM INTRINSIC CARDIAC GANGLION CONNECT WITH STELLATE GANGLION IN THE RAT

There have been many reports about the intrinsic cardiac ganglion in recent years. Most of them are ultrastructural and immunohistochemical investgations, in which many neuropeptides have been localized in the nerve cells and fibers of the mammalian heart, such as vasoactive intestinal polypeptides, neuropeptide Y, neurotensin, substance P and so on. These reports suggested that the intrinsic cardiac ganglia are not only cholinergic but have also other properties. However, their function need to be studied further. Are there any sensory neurons and interneurons which transmit information from the heart to the intrinsic or extrinsic cardiac ganglia, as well as to the central nervous system, in these ganglia? Up to now, there have been no reports about this question. In the present study, CB-HRP was injected into the     

Effect of He-Ne Laser on the Expressions of EGF and EGFR in Gastric Mucosa of Chronic Atrophic Gastritis

To investigate the histological change and the expressions of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in atrophic gastric mucosa in rats so as to appraise the effect of these regulators on the formation of atrophic gastritis, to study the expressions of EGF and EGFR in rats with chronic atrophic gastritis (CAG) after the irradiation of He-Ne laser, and to investigate the relations of He-Ne laser and precancerous lesion or apoptosis. The rats were divided into normal group, model group and laser group. The models of CAG rats were established with enema which was the mixed liquor consisted of sodium salicylate and alcohol, combined with irregular fasting and compulsive sporting as pathogenic factors. He-Ne laser(3.36 J/cm2 ) was used to irradiate CAG rats, once a day for 7 min, 20 days as a course of treatment; the expressions of EGF and EGFR were detected with immunohistochemical method. During the process of antral atrophy, the expressions of EGF and EGFR increased, they were higher in model group than those in normal group (P<0.05). After the irradiation of He-Ne laser, the expressions of EGF and EGFR were obviously lower than those in model group (P<0.05). We draw the conclusion as follows: gastric mucosa of model rat is in a hyper-proliferation status, with high protein expressions of apoptosis suppressor EGF and EGFR. CAG has some correlation with the imbalance between cell proliferation and apoptosis. He-Ne laser (3.36 J/cm2 ) can reduce the expressions of EGF and EGFR, which is an effective physiostimulator to stimulate the gastric mucosa of rat. The appropriate secretions of EGF and EGFR are propitious to the repair and regeneration for the gastric mucosa tissues, thus preventing CAG to canceration.     

Lipopolysaccharide Could Be Internalized into Human Peripheral Blood Mononuclear Cells and Elicit TNF-α Release,but not via the Pathway of Toll-Like Receptor 4 on the Cell Surface

Lipopolysaccharide(LPS),the principal component of the outer membrane of Gram-negative bacteria,stimulatesvarious cell types to release numerous proinflammatory mediators such as TNF-α,IL-6 and IL-12,which maydamage cells and lead to organ injury,even sepsis and septic shock.Toll-like receptor 4(TLR4) has beenidentified as the receptor involved in the recognition of LPS,but the role of LPS uptake in activating signaltransduction remains controversial.In the present study,TNF-α was used as a marker of macrophages/monocytes activated by LPS,and CQ was used as an inhibitor of endosome mature in order to definitude whatstage of the signal transduction elicited by LPS was interrupted.We found that there indeed existedinternalization of LPS and internalization partially participated in LPS signaling since CQ inhibited cytokinerelease,and decreased accumulation of FITC-LPS in hPBMCs.In contrast,anti-hTLR4 antibody coulddecrease cytokine release,but had no inhibition on accumulation of FITC-LPS.This result revealed thatinhibition of cytokine release was related to reduction of FITC-LPS accumulation in the cells.But TLR4 on thecell surface couldn't participate in internalization of LPS.Thus,LPS signaling and internalization couldn't beviewed as mutually independent processes.Cellular & Molecular Immunology.2004;1(5):373-377.     

Obesity as disease and as social problem

This text is part of a broader line of study that aims to analyze how and why certain eating habits and bodily practices have become social problems, as is the case with fatness. We will show that the ideas that support the definition of obesity as a chronic and avoidable disease are leading experts and health authorities, and other social workers, to know and to think about its evolution in terms of "global" illness (epidemic) and to consider cultural factors as their main cause (obesogenic environment). Paradoxically, the international and national preventive measures taken are focused on changing individual behavior and, in particular, eating habits. The concepts about the regulation of excess weight and food provide interesting information about a particular understanding of lifestyles and culture and they take into account the current promotion of health patterns.     

Guitarfish possess ipsilateral as well as contralateral retinofugal projections

Autoradiographic analysis of the primary retinal projections in the thornback guitarfish reveals both contralateral and ipsilateral projections to diencephalic, pretectal, and tegmental nuclei and the optic tectum. A total of 12 retino-recipient cell groups receive ipsilateral as well as contralateral inputs.     

Rickettsiae as organisms

Although most pathogenic rickettsiae are obligate intracellular parasites, it is clear that they are bacteria. As such, form and function in rickettsiae are closely similar to form and function found in their free-living counterparts. This review of rickettsiae as bacteria portrays the broad similarities of rickettsiae and free-living bacteria, as well as the differences which distinquish one group from the other and one rickettsia from another. Growth characteristics and requirements, ecologic influences, special adaptations, antibiotic susceptibilities and host-parasite relationships will be considered in a broad survey of likenesses and differences displayed by rickettsiae pathogenic to man.     

Sleep-dependent learning: a nap is as good as a night

The learning of perceptual skills has been shown in some cases to depend on the plasticity of the visual cortex and to require post-training nocturnal sleep. We now report that sleep-dependent learning of a texture discrimination task can be accomplished in humans by brief (60- 90 min) naps containing both slow-wave sleep (SWS) and rapid eye movement (REM) sleep. This nap-dependent learning closely resembled that previously reported for an 8-h night of sleep in terms of magnitude, sleep-stage dependency and retinotopic specificity, and it was additive to subsequent sleep-dependent improvement, such that performance over 24 h showed as much learning as is normally seen after twice that length of time. Thus, from the perspective of behavioral improvement, a nap is as good as a night of sleep for learning on this perceptual task.     

Ectosomes as immunomodulators

Considerable progress has been made in recognizing microvesicles as important mediators of intercellular communication rather than irrelevant cell debris. Microvesicles released by budding directly from the cell membrane surface (i.e., ectocytosis) either spontaneously or in response to various stimuli are called shed vesicles or ectosomes. Ectosomes are rightside-out vesicles with cytosolic content, and they expose phosphatidylserine in the outer leaflet of their membrane. Depending on their cellular origin, ectosomes have been associated with a broad spectrum of biological activities. In the light of recent findings, we now know that ectosomes derived from polymorphonuclear leukocytes, erythrocytes, platelets, and tumor cells have profound effects on the innate immune system, as well as on the induction of the adaptive immunity, globally reprogramming cells such as macrophages or dendritic cells toward an immunosuppressive and possibly tolerogenic phenotype. Although the effects observed in the circulation are mainly procoagulant and pro-inflammatory, ectosomes might be anti-inflammatory/immunosuppressive in local inflammation.     

Prostaglandins as abortifacients

Clinical trials have demonstrated the use of prostaglandins as effective abortifacients. Continuous intravenous infusion of the drugs however has been associated with certain side effects at therapeutically effective doses, such as nausea, vomiting, diarrhea and a local erythematous reaction at the site of venepuncture. Higher doses result in more serious side effects such as vasovagal symptoms, pyrexia and tachycardia. Direct application of prostaglandins E2 or F2a into the uterine cavity has been shown to minimize the side effects. Appropriate doses of prostaglandins every one or 2 hours administered at the site of action between the fetal membrane and uterine wall (via the cervix) produce the strong and frequent uterine contractions necessary for the expulsion of the products of conception. A drawback of this method is the need for the uterine cavity to be continuously monitored as dosage is determined by the uterine response. Another effective method of terminating 1st and 2nd trimester pregnacy with minimal side effects is vaginal administration (into the posterior fornix) of 50 mg PGF2a or 20 mg PGE2 every 2 or 3 hours. Single injection of prostaglandins into the amniotic sac usually results in complete abortion. The method is simple but should be used only in pregnancies of over 12 weeks' gestation as the amniotic sac is inaccessible in the 1st trimester. The prostaglandin method, compared with other methods of abortion in the 1st trimester of pregnancy (e.g., suction or dilatation and curettage) is inferior in terms of time, expense and convenience. Incomplete abortion is quite common in the 1st trimester when prostaglandins are used. With respect to 2nd trimester methods (hypertonic saline and hysterotomy) however, prostaglandins given by intravaginal, intrauterine, or intraamniotic routes offer clear advantages.     

Amplicons as vaccine vectors

HSV-1 amplicon vectors efficiently transduce cultured antigen-presenting cells (APC), including both human and murine dendritic cells as well as primary human chronic lymphocytic leukemia (CLL) B cells. Helper-free amplicons have been shown to be especially well-suited for this purpose, since they do not impair the antigen-presenting functions of these target cells. In vivo, amplicon vectors have been used in preclinical studies aimed at the development of therapeutic cancer vaccines, as well as vaccines for Alzheimer's disease, and selected microbial pathogens. Studies in small animal model systems have shown that ex vivo transduction of irradiated tumor cells with amplicon vectors encoding immunomodulatory cytokines such as IL-2 or GM-CSF can elicit protective responses against a tumor challenge. In an experimental model for cancer immunotherapy, direct transduction of preformed tumors with vectors encoding CD40L resulted in slowed tumor growth or tumor eradication. Other studies have examined the ability of amplicons to elicit immune responses against encoded antigens, and have shown that strong cellular immune responses can be generated against amplicon encoded HIV-1 antigens in mice. Thus, amplicon vectors have shown significant promise as vaccine vectors in a range of settings. These promising initial findings highlight the need to perform additional studies, including experiments to evaluate the immunogenicity of amplicon vectors in additional animal models, possibly including nonhuman primates. Overall, amplicon vectors offer compelling advantages when compared to other vaccine-delivery platforms, which include the capacity to incorporate a very large transgene payload and the potential to efficiently transduce mucosal surfaces. It will be important to design future studies to directly test and exploit these features of the amplicon system. The next few years therefore promise to be an exciting and important period in the development of amplicons as vaccine vectors.     

Stealth viruses as neuropathogens

Neuropsychiatric diseases viewed as multifaceted expression of a dysfunctional brain in which atypical responses are evoked by various sensory inputs. Disease entities have traditionally been classified according to the predominant manifestation ( ) without regard to the overlapping features of many of the diseases (+/-). Thus, mild to moderate pain, mood, cognitive, and neurosomatic symptoms are frequently present in chronic fatigue syndrome (CFS) patients. Fibromyalgia syndrome (FMS) is listed as an example of a predominantly chronic pain syndrome. Affect (mood) disorders include depression (Depress.), anxiety, panic reactions, blunted affect, mania, etc. Schizophrenia (Schizo.) is listed as an example of a major cognitive psychosis. Autism as well as various forms of dementia would be included in this category. Irritable bowel syndrome (IBS) is an example of a neurosomatic disease.     

Hospital as a temple

The present concept of hospital health care has exhausted its purpose. In a personal view as well as experience the idea "Hospital as a temple" was studied in an attempt to reconcile modern and technical with older form of health care, the latter often labelled as alternative or complementary. Both from a historical perspective as well as nowadays situation this vision is pursued.     

Why technology matters as much as science in improving healthcare

ABSTRACT: BACKGROUND: More than half a million new items of biomedical research are generated every year and added to Medline. How successful are we at applying this steady accumulation of scientific knowledge and so improving the practice of medicine in the USA? DISCUSSION: The conventional wisdom is that the US healthcare system is plagued by serious cost, access, safety and quality weaknesses. A comprehensive solution must involve the better translation of an abundance of clinical research into improved clinical practice.Yet the application of knowledge (i.e. technology) remains far less well funded and less visible than the generation, synthesis and accumulation of knowledge (i.e. science), and the two are only weakly integrated. Worse, technology is often seen merely as an adjunct to practice, e.g. electronic health records.Several key changes are in order. A helpful first step lies in better understanding the distinction between science and technology, and their complementary strengths and limitations. The absolute level of funding for technology development must be increased as well as being more integrated with traditional science-based clinical research. In such a mission-oriented federal funding strategy, the ties between basic science research and applied research would be better emphasized and strengthened.