Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death

Background  

Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations.     

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.     

Species distribution and <Emphasis Type="Italic">in vitro</Emphasis> antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

Background  

In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Novel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in health

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and additionally may provide targets for antigen-specific immune therapy. In this study, we tested 9 self-peptides derived from joint-related autoantigens for T-cell recognition (T-cell proliferative responses and cytokine production) in 36 JIA patients and 15 healthy controls. Positive T-cell proliferative responses (stimulation index ≥2) to one or more peptides were detected in peripheral blood mononuclear cells (PBMC) of 69% of JIA patients irrespective of major histocompatibility complex (MHC) genotype. The peptides derived from aggrecan, fibrillin, and matrix metalloproteinase (MMP)-3 yielded the highest frequency of T-cell proliferative responses in JIA patients. In both the oligoarticular and polyarticular subtypes of JIA, the aggrecan peptide induced T-cell proliferative responses that were inversely related with disease duration. The fibrillin peptide, to our knowledge, is the first identified autoantigen that is primarily recognized in polyarticular JIA patients. Finally, the epitope derived from MMP-3 elicited immune responses in both subtypes of JIA and in healthy controls. Cytokine production in short-term peptide-specific T-cell lines revealed production of interferon-γ (aggrecan/MMP-3) and interleukin (IL)-17 (aggrecan) and inhibition of IL-10 production (aggrecan). Here, we have identified a triplet of self-epitopes, each with distinct patterns of T-cell recognition in JIA patients. Additional experiments need to be performed to explore their qualities and role in disease pathogenesis in further detail.     

Mental practice-based rehabilitation training to improve arm function and daily activity performance in stroke patients: a randomized clinical trial

Background  

Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective.     

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.