Emotional suppression: can it predict cancer outcome in women with suspicious screening mammograms?

BACKGROUND: Previous studies have implicated emotional suppression, in particular suppression of anger, in the onset and progression of breast cancer. Many of these studies used non-standardized measures and failed to control for the effects of age and/or possible knowledge of diagnosis. The present study aimed to avoid these methodological errors in investigating the relationship of emotional suppression to a diagnosis of breast cancer in a large mammography screened population. METHOD: Data were collected from 1151 women with suspicious mammograms recalled to a breast screening programme. Prior to multidisciplinary assessment women were asked to complete the Courtauld Emotional Control Scale. Imaging assessment outcome data and biopsy results were collected. RESULTS: Fifteen per cent of this population subsequently were diagnosed with breast cancer. There were no significant associations between a cancer outcome and emotional suppression before or after the highly significant effect of age was taken into account. CONCLUSIONS: These results suggest that suppression of emotion may not be relevant to the development of breast cancer. Its role in the progression of existing disease requires clarification.     

Hematopoietic stem cells: can old cells learn new tricks?

Since the establishment of cell lines derived from human embryonic stem (ES) cells, it has been speculated that out of such "raw material," we could some day produce all sorts of replacement parts for the human body. Human pluripotent stem cells can be isolated from embryonic, fetal, or adult tissues. Enormous self-renewal capacity and developmental potential are the characteristics of ES cells. Somatic stem cells, especially those derived from hematopoietic tissues, have also been reported to exhibit developmental potential heretofore not considered possible. The initial evidences for the plasticity potential of somatic stem cells were so encouraging that the opponents of ES cell research used them as arguments for restricting ES cell research. In the past months, however, critical issues have been raised challenging the validity and the interpretation of the initial data. Whereas hematopoietic stem-cell therapy has been a clinical reality for almost 40 years, there is still a long way to go in basic research before novel therapy strategies with stem cells as replacement for other organ systems can be established. Given the present status, we should keep all options open for research in ES cells and adult stem cells to appreciate the complexity of their differentiation pathways and the relative merits of various types of stem cells for regenerative medicine.     

Glucose-transport regulation in leukemic cells: how can H2O2 mimic stem cell factor effects?

In leukemic cells, glucose transport is activated by SCF and H2O2 through a common signal cascade involving Akt, PLCgamma, Syk, and the Src family, in this order. An explanation can be provided by the phosphorylation of c-kit, the SCF receptor, elicited by either SCF or H2O2. Moreover, antioxidants prevent the SCF effect on glucose transport, confirming the involvement of H2O2 in the pathway leading to glucose-transport activation and suggesting a potential role for reactive oxygen species in leukemia proliferation.     

Chlamydia trachomatis in the endometrium: can surgical pathologists identify plasma cells?

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease. The authors examined the relation between chronic endometritis, which they term plasma cell endometritis (PCE), and chlamydial infection using plasmid-based polymerase chain reaction (PCR) and immunohistochemical staining (IHC) of paraffin-embedded endometrial sections. C. trachomatis infection was detected in 5 (24%) of 21 cases of PCE and in 1 (4%) of histologically normal endometrium. The diagnosis of chronic endometritis (with plasma cells confirmed by methyl green pyronin staining) was correctly made in 74% of the cases originally diagnosed as PCE and in 23% of control cases originally diagnosed as normal. The authors conclude that the histopathologic finding of plasma cells in endometrial samples should encourage further examination for chlamydial infection.     

Peritoneal dialysis-related peritonitis: can we predict it?

Peritonitis complicating peritoneal dialysis represents a major cause of technique failure, hospitalization, and increased mortality. Peritonitis tends to be recurrent and clustered within particular patients at risk. The aim of this review is to evaluate the potential predictive factors for development of peritoneal dialysis-associated peritonitis based on currently available evidence. Risk factors were divided into medical and non-medical ones, and characterized by a schema of fixed versus modifiable factors. A new direction in the landscape change of the risk factors of peritonitis appears to focus on psychosocial aspects and patient training. Identification of these factors have important clinical implications because of the hitherto lack of well-established strategies to prevent peritonitis complicating peritoneal dialysis. It is hoped that better understanding of the risk factors will allow us to take tangible steps toward minimizing the infectious burden from the Achilles' heel of peritoneal dialysis.     

HLA class I antigen expression in malignant cells: why does it not always correlate with CTL-mediated lysis?

HLA class I antigen defects are frequently found in malignant cells. They appear to play a role in the clinical course of the disease, probably because they provide tumor cells with a mechanism to escape cytotoxic T lymphocyte (CTL) recognition and destruction. Expression of HLA class I antigens, however, is not always associated with the susceptibility of tumor cells to CTL lysis. Many mechanisms may underlie this finding, including the lack of tumor antigen (TA)-derived peptide presentation by a given HLA class I allospecificity, and/or the expression of immunosuppressive molecules such as HLA-G. These findings emphasize the need to develop probes to measure HLA class I allospecificity-TA peptide complex expression in malignant cells. Furthermore, the evaluation of the role of HLA class I antigens in the interaction of malignant cells with host immune cells should take into account the potential interference of tumor-derived immunomodulators.     

'Necrosome'-induced inflammation: must cells die for it?

Necrosis, a form of death characterized by rupture of the cell membrane, is closely interlinked with inflammation. Cellular components released during necrotic death can trigger inflammation. Conversely, inflammation often yields tissue damage and, as a consequence, cell death. Which occurs first--necrosis or inflammation--in specific in vivo situations is currently difficult to tell. A way out of this 'chicken-and-egg' conundrum may be found via the recent finding that both necrotic cell death and inflammation can be initiated by a distinct set of signaling proteins, the 'necrosome', that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. Further clarifying the function of these signaling proteins should make it possible to establish when they induce inflammation directly and when inflammation is caused by necrotic cell death.     

Defining psychology: what can it do for us?

"Psychology," like many abstract terms, is difficult to define precisely. Henriques' (this issue) argument that psychology, though unified and coherent, actually spans two realms-psychological formalism ("the science of mind," this issue) and human psychology ("the science of human behavior at the individual level," this issue)-seems likely to improve the clarity of the concept. The strongest contribution of his analysis may be its placing "psychology" in the larger conceptual framework of the Tree of Knowledge taxonomy.     

Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?

The discovery that mesenchymal stem cells (MSCs) are recruited into tumors has led to a great deal of interest over the past decade in the function of MSCs in tumors. To address this, investigators have used a variety of tumor models in which MSCs are added exogenously to determine their impact on tumor development. Interestingly, many studies have reported contradicting results, with some investigators finding that MSCs promote tumor growth and others reporting that MSCs inhibit tumor growth. Many mechanisms have been reported to account for these observations, such as chemokine signaling, modulation of apoptosis, vascular support, and immune modulation. In this review, we analyzed the differences in the methodology of the studies reported and found that the timing of MSC introduction into tumors may be a critical element. Understanding the conditions in which MSCs enhance tumor growth and metastasis is crucial, both to safely develop MSCs as a therapeutic tool and to advance our understanding of the role of tumor stroma in carcinogenesis.     

Unexplained recurrent miscarriage: how can we explain it?

Unexplained recurrent miscarriage (RM) can be a challenging and frustrating condition for both patients and clinicians. For the former, there is no diagnosis available for consolation, while for the latter there is little evidence-based treatment to offer. However, the majority of these patients have an excellent prognosis without the need for any treatment. Epidemiological associations suggest that the reason for this is that the majority of women with unexplained RM are in fact healthy individuals, with no underlying pathology, who have suffered three miscarriages purely by chance. Nevertheless, a certain proportion of women with unexplained RM will continue to miscarry, and preliminary studies suggest the presence of pathology in some women of this group. As a result, two types of unexplained RM can be described: Type I unexplained RM, which occurs by chance in women who have no underlying pathology and has a good prognosis; and Type II unexplained RM, which occurs due to an underlying pathology that is currently not yet identified by routine clinical investigations and has a poorer prognosis. Distinguishing between Types I and II unexplained RM can be achieved by considering several factors: the age of the woman, the definition used for RM (i.e. whether biochemical pregnancy losses are considered as miscarriages), the number of previous miscarriages suffered and the karyotype of the products of conception, where available. A better understanding of the two types of unexplained RM could lead to more targeted referrals, investigations and treatments, which would improve cost-effectiveness and overall clinical care.     

Mast cells participate in allograft rejection: can IL-37 play an inhibitory role?

Objective

The aim of this study was to evaluate the role of mast cells (MCs) in allograft rejection, eventually inhibited by IL-37. Immune cells including MCs participate in allograft rejection by generating IL-1, IL-33, TNF and other cytokines.

Methods

We evaluated allograft rejection on the experience of our experimental data and using the relevant literature.

Results

MCs are involved in initiation and regulation of innate and adaptive immune responses-pathways. MCs are important pro-inflammatory cells which express high-affinity receptor FceRI and can be activated by IgE and some pro-inflammatory cytokines, such as IL-1 and IL-33. The cross-linkage of high affinity IgE receptor on MCs by antigen ligation has a crucial role in allergy, asthma, anaphylaxis, cancer and allograft rejection. MCs mediate immunity in organ transplant, leading to the activation of allospecific T cells implicated in the rejection and generate pro-inflammatory cytokines/chemokines. IL-1 pro-inflammatory cytokine family members released by MCs mediate allograft rejection and inflammation. IL-37 is also an IL-1 family member generated by macrophage cell line in small amounts, which binds to IL-18Rα and produces an anti-inflammatory effect. IL-37 provokes the inhibition of TLR signaling, TLR-induced mTOR and (MyD88)-mediated responses, suppressing pro-inflammatory IL-1 family members and increasing IL-10.

Conclusion

IL-37 inhibition offers the opportunity to immunologically modulate MCs, by suppressing their production of IL-1 family members and reducing the risk of allograft rejection, resulting as a potential good therapeutic new cytokine. Here, we report the relationship between inflammatory MCs, allograft rejection and pro-inflammatory and anti-inflammatory IL-37.

     

Review article: cyclic AMP sensors in living cells: what signals can they actually measure?

Cyclic AMP is a ubiquitous intracellular second messenger that transmits information to several proteins including cyclic nucleotide-gated ion channels and protein kinase A (PKA). In turn, these effectors regulate such diverse cellular functions as Ca²⁺ influx, excitability, and gene expression, as well as cell-specific processes such as glycogenolysis and lipolysis. The enzymes known to regulate cAMP levels, adenylyl cyclase and phosphodiesterase, have been studied in detail. Unfortunately, an understanding of how information is encoded within cAMP signals has been elusive, because, until recently, methods for measuring cAMP lacked both spatial and temporal resolution. In this paper, we describe two recently developed methods for detecting cAMP levels in living cells. The first method measures fluorescence energy transfer between labeled subunits of PKA. This method is particularly useful for monitoring cellular localization of PKA activity following increases in cAMP levels. However, the slow activation and deactivation rates, the necessarily high concentrations of labeled subunits, and the redistribution of labeled subunits throughout the cell, all intrinsic to this method, limit its utility as a cAMP sensor. The second method uses genetically modified cyclic nucleotide-gated channels to measure plasma membrane-localized cAMP levels in either cell populations or single cells. The rapid gating kinetics of these channels allow real-time measurement of cAMP concentrations. These methods have given us the first glimpses of cAMP signals within living cells. © 2002 Biomedical Engineering Society. PAC2002: 8716Uv, 8780-y, 8716Sr     

Metronomic chemotherapy and anti‐angiogenesis: can upgraded pre‐clinical assays improve clinical trials aimed at controlling tumor growth?

Metronomic chemotherapy, which is continuously administered systemically at close to non‐toxic doses, targets the endothelial cells (ECs) that are proliferating during tumor angiogenesis. This leads to harmful effects of an even greatly increased number contiguous tumor cells. Although pre‐clinical studies of angiogenesis‐related EC features in vitro and of the anti‐angiogenic and anti‐tumor effects in vivo of metronomic chemotherapy have provided valuable insights, clinical trials with this type of therapy have been less successful in inhibiting tumor growth. One possible reason for the apparent disconnect between the pre‐clinical and clinical outcomes is that most of the currently used experimental angiogenesis assays and tumor models are incapable of yielding data that can be translated readily into the clinical setting. Many of the assays used suffer from unintentional artifactual effects, e.g., oxidative stress in vitro, and inflammation in vivo, which reduces the sensitivity and discriminatory power of the assays. Co‐treatment with an antioxidant or the inclusion of antioxidants in the vehicle often significantly affects the angiogenesis‐modulating outcome of metronomic mono‐chemotherapy in vivo. This ‘metronomic chemotherapy vehicle factor’ merits further study, as do the observations of antagonistic effects following metronomic treatment with a combination of standard chemotherapeutic drugs in vivo.     

Reactivity of measurement in health psychology: How much of a problem is it? What can be done about it?

Purpose. Measurement reactivity is defined as being present where measurement results in changes in the people being measured. The main aim of this review is to provide an overview of the current state of knowledge concerning the extent and nature of psychological measurement affecting people who complete the measures. Other aims are to describe how this may affect conclusions drawn in health psychology research and to outline where more research is needed. Methods. Narrative review. Results. Several studies, using a variety of methods, have found measurement procedures to alter subsequent cognition, emotion, and behaviour. In many instances, the effects obtained were of up to medium size. However, the extent to which such studies are representative is not clear: do other studies which find no reactive effects of measurement not exist or do they exist but are not reported? Conclusions. Although measurement reactivity can yield medium‐sized effects, our understanding of this phenomenon is still rudimentary. We do not know the precise circumstances that are likely to result in measurement reactivity: we cannot predict when problems are more likely to arise. There is a particular absence of studies of the mechanisms by which measurement reactivity arises. There is a need for a systematic review of this literature, which should aim to quantify the extent of measurement reactivity effects and to provide a firmer evidence base for theorizing about the sources of reactivity.