The Ifi 200 genes: an emerging family of IFN-inducible genes

The biological activities of interferons (IFNs) are mediated by IFN-induced proteins. One family is encoded by several structurally related genes located on murine chromosome 1 (Ifi 200 cluster) and three homologous genes (MNDA, IFI 16 and AIM2) located on human chromosome 1 as well, within a linkage group highly conserved between mouse and human. All the proteins of this family contain at least one copy of a conserved 200 amino acid domain, in addition to other regions that are different or missing among the various family members. Conservation of the 200 amino acid segment, therefore, may be responsible for a common function, while individually expressed domains may afford other tissue- or cell-specific functions. The data available demonstrate that at least two members of the Ifi 200 protein family, p202 and p204, inhibit cell proliferation in vitro. Moreover, high constitutive levels of p204 expression impair normal embryo development in transgenic animals. Here, we will review the principal features of murine and human proteins belonging to this family and their function in the cell growth-regulatory activities mediated by IFNs.     

Autocrine regulation of keratinocytes: the emerging role of heparin-binding, epidermal growth factor-related growth factors

Two hundred and ninety-seven consecutive Charnley total hip replacements that had been followed for at least twenty years or until revision or death were analyzed to determine the effect of early debonding of the smooth-surfaced femoral component on its subsequent survival. Radiographically evident debonding was not found to have a significant effect, with the numbers available, on the long-term survival of the femoral component when the maximum thickness of the radiolucent line between the superolateral border of the prosthesis and the cement had been less than 2.0 millimeters during the first one to five years after the operation. The radiographic finding of debonding also was not found to be associated with pain in the hip. These data show that most components with early debonding functioned well during a long period of follow-up and suggest that debonding of a smooth femoral component of a Charnley total hip replacement should not be considered to be analogous to loosening. In contrast, when the maximum thickness of the radiolucent line between the superolateral border of the prosthesis and the cement was 2.0 millimeters or more, an early appearance of debonding was associated with a significantly poorer (p < 0.0001) probability of survival of the Charnley femoral component without revision because of aseptic loosening. Thus, pronounced early subsidence of the component within the cement mantle had a strong negative impact on the long-term performance of the implant. The results of the present study should not be extrapolated to prostheses with substantially different design characteristics, as it appears that different types of femoral components behave differently when debonding occurs.     

Serial marriage: A heuristic analysis of an emerging family form.

We discuss serial marriage, defined as three or more marriages as a result of repeated divorce, from a heuristic perspective. We estimate the prevalence of the phenomenon and advance hypotheses based on existing empirical, clinical, and theoretical work concerning the development of this life-style and its consequences for family members. We discuss possible outcomes of children in serial marriage families. We present conceptual and theoretical considerations for the study of serial marriage, as well as suggestions for future research directions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of prostatic growth and function by peptide growth factors

Polypeptide growth factors are positive and negative regulators of prostatic growth and function. Expression and biological effects of epidermal growth factor (EGF), transforming growth factors (TGFs) alpha and beta, fibroblast growth factors (FGFs), and insulin-like growth factors (IGFs) in the prostate have been extensively studied. EGF and TGF alpha, which share the same receptor, are strong mitogens for prostatic epithelial and stromal cells. Their paracrine mode of action in normal tissue and early-stage tumors is apparently altered towards an autocrine stimulation in hormone-independent tumors, which gain the ability to produce TGF alpha by themselves. TGF beta has a dual role in the regulation of prostatic growth. It inhibits growth of prostatic epithelial cells in culture and mediates programmed cell death after androgen withdrawal. However, advanced prostatic carcinomas become insensitive to the inhibitory effect of TGF beta. Several members of the FGF family have been identified in the prostate. They are mainly or exclusively expressed in the stromal cells, and stimulate the epithelial cells. In the rat Dunning tumor model, progression is accompanied by distinct changes in the expression of FGFs and their receptors. In the hyperplastic tissue, basic FGF (bFGF) is accumulated. This growth factor is also a potent angiogenic inducer, expression of which may determine the metastatic capability of a tumor. IGFs are paracrine growth stimulators in the normal and hyperplastic prostate. It is still under consideration whether prostatic cancer cells gain the ability to produce IGF-I by themselves and thus shift to an autocrine mode of IGF-I stimulation. Growth factors also interact with the androgen-signaling pathway. IGF-I in particular, other growth factors as well, can activate the androgen receptor.     

Lectin activities of cytokines and growth factors: function and implications for pathology

The discovery that certain cytokines have carbohydrate-binding (lectin) properties opens new concepts in the understanding of their mechanism of action. The carbohydrate-recognition domain, which is localized opposite to the receptor-binding domain, makes these molecules bi-functional. The expression of the biological activity of the cytokine relies on its carbohydrate-binding activity which allows the association of the cytokine receptor with molecular complexes comprising the specific kinase involved in receptor phosphorylation and in specific signal transduction. It is expected that blood accumulation of free or membrane-bound glucan ligands of cytokines may dramatically perturb their endogenous function inducing specific immunodeficiencies.     

Survivors of childhood cancer and comparison peers: The influence of early family factors on distress in emerging adulthood.

This prospective study examines family predictors of distress among survivors of childhood cancer and comparison peers during the transition to emerging adulthood. Children with cancer (n = 55), comparison peers (n = 60), and parents completed measures of distress, family environment, social support, and demographic characteristics during initial treatment, as well as follow-up measures of young adult distress and demographic characteristics soon after participants turned 18 years old. Severity of initial treatment and late effects were rated by healthcare providers for participants with cancer. For all participants, mother and father report of initial parent distress was associated with their report of young adult distress at follow-up. Young adult gender moderated this association. For survivors of childhood cancer, severity of initial treatment and late effects also moderated the association between parent and young adult distress. Improving parent distress may help reduce child distress in general. For survivors specifically, ameliorating the impact of initial treatment and long-term physical problems may be beneficial. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tuberculosis in the newborn: an emerging disease

During the last three years 172 diagnostic laparoscopies (DL) were performed at our department in patients with an acute abdomen of unclear causes. This corresponds to 17% of all patients who underwent operation due to an acute abdomen in the same period. Always the indication for a diagnostic laparoscopy arose then, when the cause or the localization of the acute abdomen could not be found by conventional diagnostic methods. The advantages of DL were either the confirmation (93%) or the exclusion (7%) of the diagnosis "acute abdomen", the exact localization and simultaneously a definitive operative treatment of the cause by minimal invasive interventions (n = 109/65%). In these patients with acute abdomen the main causes were acute inflammations of gallbladder (n = 48) and appendix (n = 29), ulcus perforations (n = 9) and ileus (n = 9). The conversion rate amounted to 2.7%, the postoperative complication rate to 11% and the lethality rate to 1.8% in these patients. A new indication is the so-called "bedside laparoscopy" as means to control the postoperative course of mesenteric embolism (n = 9) and diffuse peritonitis (n = 3) in order to avoid the stress of a second-look operation for these seriously ill patients or to secure the indication for relaparotomy.     

Cognitive function as an emerging treatment target for marijuana addiction.

Cannabis is the most widely used illicit substance in the world, and demand for effective treatment is increasing. However, abstinence rates following behavioral therapies have been modest, and there are no effective pharmacotherapies for the treatment of cannabis addiction. We propose a novel research agenda and a potential treatment strategy, based on observations that both acute and chronic exposure to cannabis are associated with dose-related cognitive impairments, most consistently in attention, working memory, verbal learning, and memory functions. These impairments are not completely reversible upon cessation of marijuana use, and moreover may interfere with the treatment of marijuana addiction. Therefore, targeting cognitive impairment associated with chronic marijuana use may be a promising novel strategy for the treatment of marijuana addiction. Preclinical studies suggest that medications enhancing the cholinergic transmission may attenuate cannabis-induced cognitive impairments, but these cognitive enhancing medications have not been examined in controlled human studies. Preliminary evidence from individuals addicted to other drugs suggests that computerized cognitive rehabilitation may also have utility to improve cognitive function in marijuana users. Future clinical studies optimally designed to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these treatments for marijuana addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimer's disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons.     

Quantitative risk assessment: an emerging tool for emerging foodborne pathogens

New challenges to the safety of the food supply require new strategies for evaluating and managing food safety risks. Changes in pathogens, food preparation, distribution, and consumption, and population immunity have the potential to adversely affect human health. Risk assessment offers a framework for predicting the impact of changes and trends on the provision of safe food. Risk assessment models facilitate the evaluation of active or passive changes in how foods are produced, processed, distributed, and consumed.     

Aminopeptidases: structure and function

Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Several aminopeptidases perform essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes and are inhibited by the transition-state analog bestatin. Some are monomeric, and others are assemblies of relatively high mass (50 kDa) subunits. cDNA sequences are available for several aminopeptidases, and a 3-dimensional structure is available for the bovine lens enzyme. Crystallographic, electron micrographic, NMR, and photoaffinity labeling studies indicate that lens leucine aminopeptidase protomers are bilobal and that bestatin and substrates are bound in an active site, which is found in the larger lobe on each protomer. Zn2+ is involved in substrate liganding in most aminopeptidases. There is no evidence of an acyl-enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate some amino acid sequence homologies in organisms as diverse as Escherichia coli and mammals, particularly in catalytically important residues or in residues involved in metal ion binding.     

Acting up and physical illness: temporal patterns and emerging structure

Many psychoanalytic writers have viewed acting out and somatization as alternate routes for the discharge of uncontained aggressive impulses in borderline patients. In order to investigate this empirically, we tracked the occurrence of two related behaviors--acting up and physical illness--over the course of one patient's long-term hospitalization. Daily scores on these variables were analyzed using a time series procedure. Results indicated that as treatment progressed, acting up and physical illness became more synchronized, and this occurred just prior to symptom remission. Material from psychotherapy suggested that these behavioral changes were associated with the patient's increased ability to verbalize aggressive impulses in the context of fantasy and memory.     

Pleiotrophin and midkine, a family of mitogenic and angiogenic heparin-binding growth and differentiation factors

The lipid emulsions used in parenteral nutrition are constituted of particles rich in triacylglycerols (TAG) called artificial chylomicrons (200-500 nm in diameter; monolayer of phospholipids [PL] enveloping a TAG core) and PL-rich particles called liposomes (diameter inferior to 80 nm; bilayer of PL around an aqueous phase), which represent the excess emulsifier. Introduced into the circulation, the two populations of particles come into contact with circulating lipoproteins and cell membranes and experience the same overall fate: exchanges and transfers of lipids and apolipoproteins, enzymatic hydrolysis of TAG and PL, and internalization by different tissues. The relative importance of these different metabolic processes varies depending on the type of particle. The artificial chylomicrons undergo a hydrolysis of their TAG by lipoprotein lipase, with a release of fatty acids and formation of smaller particles of remnants, which are rapidly removed by the liver. In delivering fatty acids to the tissue, artificial chylomicrons fulfill an energy transport function similar to the natural chylomicrons. The liposomes hold little energy interest, and they also have deleterious effects when infused in excess. They inhibit the lipolysis of artificial chylomicrons and, by actively capturing endogenous cholesterol, they stimulate tissue cholesterogenesis and accumulate in the blood as lipoprotein-X, a long-lived abnormal lipoprotein. To limit as much as possible the metabolic perturbations due to the intravenous administration of exogenous PL, the emulsion has to be infused at a low rate, and should contain the minimal amount of excess PL.     

Regulation of metabolism and growth during immune challenge: an overview of cytokine function

Commercially reared food animals encounter serial pathogenic and nonpathogenic immune challenges throughout production. Because of the diversion of nutrients away from growth in support of immune-related processes, immune challenge is considered a major obstacle to animals' achieving their genetic potential for growth or efficiency of gain. Scientists now recognize that many metabolic processes respond directly or indirectly to proinflammatory cytokines. This cytokine-mediated "reprogramming" of metabolism is a homeorhetic mechanism that ensures an adequate supply of nutrients for proliferation of lymphocyte and macrophage populations, antibody production, and hepatic synthesis of acute phase proteins. Proinflammatory cytokines have been linked to altered nutrient uptake and utilization. Anabolic processes are interrupted, and companion catabolic activities are amplified. Furthermore, cytokines may influence prenatal growth and development, and to the extent that postnatal proliferation and differentiation of myogenic and adipogenic cells contribute to postnatal growth, cytokine regulation of these events may ultimately influence growth. The following discussion is an overview of the impact of immune challenge and proinflammatory cytokines on metabolism and growth.