Plasmapheresis in a very young infant with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, the pathogenesis of which is unclear. Plasma transfusions and plasmapheresis are widely used modes of therapy for adults with this life-threatening syndrome. There is very limited experience in using plasmapheresis therapy in children and infants with atypical HUS. Plasmapheresis, which is considered a relatively safe procedure in adults and older children, may be hazardous in neonates and very young infants and can result in severe complications. We report a 2-month-old infant with idiopathic atypical HUS, who was successfully treated with a 1-month course of plasmapheresis during the acute phase of the disease. Appropriate preparations as well as several adjustments were made in order to meet the special needs of this very young infant who, to the best of our knowledge, is the youngest reported patient with atypical HUS to undergo plasmapheresis. Plasmapheresis therapy of the infant was not associated with any complications of the procedure and resulted in marked clinical improvement. We conclude that plasmapheresis in neonates and in very small infants is technically feasible, can be performed without major complications, and may be of benefit in individual cases. Received: 11 November 1999 / Revised: 3 August 2000 / Accepted: 10 August 2000     

Induction of apoptosis by adenovirus E4orf4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A

We previously have shown that adenovirus type 5 E4orf4 protein associates with protein phosphatase 2A (PP2A) and induces apoptosis in transformed cells in a p53-independent manner. Here we show that the interaction between E4orf4 and PP2A is required for induction of apoptosis by the viral protein. This conclusion is supported by a mutation analysis of E4orf4 protein, showing a correlation between the ability to bind PP2A and to induce apoptosis, and by the observation that transfection of an antisense construct of the PP2A-B55 subunit reduces expression of the PP2A-B55 subunit and inhibits induction of apoptosis by E4orf4, but not by p53. The mutant analysis also indicates that even a low level of interaction with PP2A is sufficient to initiate the E4orf4 apoptotic pathway. In addition, E4orf4 inhibits cellular transformation by various oncogenes, and this function is coupled to its ability to induce apoptosis. Furthermore, expression of oncogenes in primary cell cultures sensitizes these cells to induction of apoptosis by E4orf4. Our results suggest that E4orf4 is a potentially useful tool for cancer gene therapy.     

Intermodal matching of emotional expressions in young children with autism

This study examined the ability of young children with autism spectrum disorders (ASD) to detect affective correspondences between facial and vocal expressions of emotion using an intermodal matching paradigm. Four-year-old children with ASD (n = 18) and their age-matched normally developing peers (n = 18) were presented pairs of videotaped facial expressions accompanied by a single soundtrack matching the affect of one of the two facial expressions. In one block of trials, the emotions were portrayed by their mothers; in another block of trials, the same emotion pairs were portrayed by an unfamiliar woman. Findings showed that ASD children were able to detect the affective correspondence between facial and vocal expressions of emotion portrayed by their mothers, but not a stranger. Furthermore, in a control condition using inanimate objects and their sounds, ASD children also showed a preference for sound-matched displays. These results suggest that children with ASD do not have a general inability to detect intermodal correspondences between visual and vocal events, however, their ability to detect affective correspondences between facial and vocal expressions of emotions may be limited to familiar displays.     

Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice.

Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.     

Increased serum C-reactive protein levels are associated with shorter survival and development of second cancers in chronic lymphocytic leukemia

Background: Chronic lymphocytic leukemia (CLL) is characterized by a heterogeneous clinical course, ranging from stable to more aggressive disease. Herein, we determined the prognostic significance of serum C-reactive protein (CRP) levels in patients with CLL

Methods: A retrospective cohort study reviewing the records of 107 consecutive treatment naïve patients with CLL and a control group comprised of apparently healthy individuals attending for periodic health examinations.

Results: The median CRP level of patients with CLL was 0.19?mg/dL (0–2.9). In univariate analysis, high-CRP levels (≥0.4 mg/dL) were significantly associated with an increased risk of mortality (HR?=?3.97, 95%CI 1.64–9.62, p?=?.002) and development of second solid cancers (HR?=?4.54, 95%CI 1.57–13.11, p?=?.005), compared to low-CRP values (<0.4 mg/dL). In multivariate analysis, high-CRP retained statistical significance for all-cause mortality (HR?=?2.81, 95%CI 1.04–7.57, p?=?.04) and the development of second solid malignancies (HR?=?4.54, 95%CI 1.57–13.11, p?=?.005). Moreover, when compared to an apparently healthy population, CLL patients with high CRP levels had more than an eightfold risk of cancer.

Conclusions: Elevated baseline CRP levels are associated with shorter survival and development of second cancers in patients with CLL. We suggest that increased CRP in patients with CLL may justify a more rigorous search for second cancers.

• KEY MESSAGES

• Elevated CRP levels are associated with a shorter overall survival in CLL.

• Elevated CRP levels are associated with an increased risk of second cancers in CLL.

• Increased CRP in patients with CLL may justify a more rigorous search for second cancers.

     

Kaposi's sarcoma-associated herpesvirus: clinical, diagnostic, and epidemiological aspects

Kaposi's sarcoma-associated herpesvirus (KSHI) is one of the few viruses proven to be associated with tumorigenesis in humans. Its causal association with all clinical and epidemiological variants of Kaposi's sarcoma (KS) is well established. KSHV is also involved in the pathogenesis of primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease (MCD). Possible associations of KSHV with other clinical settings have been extensively examined. The findings from several of these studies are contradictory and are yet to be resolved. Concentrated effort over the last decade, since the initial discovery of KSHV, led to the development of several experimental systems that resulted in a better comprehension of the biological characteristics of KSHV and set the stage for the understanding of mechainisms by which diseases are induced by the virus. The development of molecular, histological, and serological tools for KSHV diagnosis allowed researchers to track the transmission and to study the epidemiology of KSHV. These assays have been applied, in particular in ambiguous cases, in order to confirm clinically and pathologically based diagnoses. Here, we review the advances in the clinical, experimental, diagnostic, and epidemiological research of KSHV.     

Establishing a high level of knowledge regarding bioterrorist threats in emergency department physicians: methodology and the results of a national bio-preparedness project

INTRODUCTION: Medical systems worldwide are facing the new threat of morbidity associated with the deliberate dispersal of microbiological agents by terrorists. Rapid diagnosis and containment of this type of unannounced attack is based on the knowledge and capabilities of medical staff. In 2004, the knowledge of emergency department physicians of anthrax was tested. The average test score was 58%. Consequently, a national project on bioterrorism preparedness was developed. The aim of this article is to present the project in which medical knowledge was enhanced regarding a variety of bioterrorist threats, including cutaneous and pulmonary anthrax, botulinum, and smallpox. METHODS: In 2005, military physicians and experts on bioterrorism conducted special seminars and lectures for the staff of the hospital emergency department and internal medicine wards. Later, emergency department senior physicians were drilled using one of the scenarios. RESULTS: Twenty-nine lectures and 29 drills were performed in 2005. The average drill score was 81.7%.The average score of physicians who attended the lecture was 86%, while those who did not attend the lectures averaged 78.3% (NS). CONCLUSIONS: Emergency department physicians were found to be highly knowledgeable in nearly all medical and logistical aspects of the response to different bioterrorist threats. Intensive and versatile preparedness modalities, such as lectures, drills, and posters, given to a carefully selected group of clinicians, can increase their knowledge, and hopefully improve their response to a bioterrorist attack.     

RBL cells as models for in vitro studies of mast cells and basophils

Since their establishment in 1981, RBL-2H3 cells have been widely used as a mast cell (MC) model. Their ability to be easily grown in culture in large amounts, their responsiveness to FcεRI-mediated triggers and the fact that they can be genetically manipulated, have provided advantages over primary MCs, in particular for molecular studies relying on genetic screening. Furthermore, the ability to generate clones that stably express proteins of interest, for example, a human receptor, have marked the RBL cells as an attractive MC model for drug screening. Indeed, 3 RBL reporter cell lines (RS-ATL8, NFAT-DsRed, and NPY-mRFP) have been generated providing useful models for drug and allergen screening. Similarly, RBL cells stably expressing the human MrgprX2 receptor provide a unique paradigm for analyzing ligand interactions and signaling pathways of the unique human receptor. Finally, transient co-transfections of RBL cells allow functional genomic analyses of MC secretion by combining library screening with simultaneous expression of a reporter for exocytosis. RBL cells thus comprise powerful tools for the study of intracellular membrane trafficking and exocytosis and the detection of allergens, vaccine safety studies and diagnosis of allergic sensitization. Their recent uses as an investigative tool are reviewed here.