A comparison of two anti-neuraminidase monoclonal antibodies by complement activation

The specificities of two anti-neuraminidase monoclonal antibodies have been compared by their ability to fix complement. They were found to differ to some extent in their reactivity with a range of N2 influenza viruses. Thus, as in the case of anti-hemagglutinin antibodies, anti-neuraminidase monoclonal antibodies are able to detect subtle structural changes in the viral antigen. Although both monoclonal antibodies fixed complement with intact virus, neither one fixed complement when complexed with isolated neuraminidase “heads”.     

Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation

The recent improvements in the treatment of cancer by chemo- and radiotherapy have led to a significant increase in the survival rates of patients with malignant disease, but at the expense of distressing side effects. One major problem, especially for younger patients, is that aggressive therapy destroys a significant proportion of the follicular population, which can result in either temporary or permanent infertility. Freeze-banking pieces of ovarian cortex prior to treatment is one strategy for preserving fecundity. When the patient is in remission, fertility could, theoretically, be restored by autografting the thawed tissue at the orthotopic site or by growing isolated follicles to maturity in vitro. Recent studies have found good follicular survival in frozen-thawed human ovarian tissue but to optimize the process an effective cryopreservation method needs to be developed. An essential part of such a technique is to permeate the tissue with a cryoprotectant to minimize ice formation and the extent of this equilibration is an important determinant of post-thaw cellular survival. In the current study, we have investigated the diffusion of four cryoprotective agents into human tissue at both 4 degrees C and 37 degrees C. We have also studied the effect of adding different concentrations of the non penetrating cryoprotective agent, sucrose, to the freezing media using the release of lactate dehydrogenase as a measure of its protective effect. At 4 degrees C propylene glycol and glycerol penetrated the tissue significantly slower than either ethylene glycol or dimethyl sulphoxide. At the higher temperature of 37 degrees C all four cryoprotectants penetrated at a faster rate, however concern about enhanced toxicity prevents the use of these conditions in practice. Thus, the results suggest that the best method of preparing tissue for freezing is exposure for 30 min to 1.5 M solutions of ethylene glycol or dimethyl sulphoxide at 4 degrees C; this achieved a mean tissue concentration that was almost 80% that of the bathing solution. We also report that the addition of low concentrations of sucrose to the freezing medium does not have a significant protective effect against freezing injury.      

Assessment of Self-Reward Strategies for Maintenance of Breast Self-Examination

This study examined the relative impact of different self-reward strategies on maintenance of breast self-examination (BSE) practice among 1649 women trained to do BSE. Training groups were randomized into four conditions: (a) self-reward instructions and materials delivered at the end of the BSE training session; (b) self-reward suggestions delivered through the mail each month, contingent upon the BSE performance; (c) external monetary rewards and self-reward suggestions delivered through the mail each month on an intermittent schedule, contingent upon BSE practice; and (d) a no-reward control condition. Follow-up assessments 12 months following training revealed a pattern of evidence in support of the benefits of external monetary rewards and self-reward prompts on BSE frequency and quality; however, it is likely that the value of that condition lies in the external reward component.     

Life events and depression in a community sample of siblings

BACKGROUND: The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. METHODS: We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. RESULTS: Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. CONCLUSIONS: Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features

Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.     

Nano-structured polymers enhance bladder smooth muscle cell function

It is the hypothesis of the present study that a biocompatible material which mimics the nanometer topography of native bladder tissue will enhance cellular responses and lead to better tissue integration in vivo. Previous in vitro studies have verified the ability to successfully reduce the surface feature dimensions of poly(lactic-co-glycolic acid) (PLGA) and poly(ether urethane) (PU) films into the nanometer regime via chemical etching procedures. Results from these studies also provided the first evidence that bladder smooth muscle cell adhesion was enhanced on chemically treated nano-structured polymeric surfaces compared to their conventional counterparts. Although cell adhesion is necessary for a biomaterial's success, subsequent cell functions (such as long-term cell growth and proliferation) are also critical for tissue ingrowth and long-term implant survival. The present in vitro study, therefore, investigated the function of bladder smooth muscle cells on these novel, nano-structured polymers over the expanded periods of 1, 3 and 5 days. Results indicated that cell number was influenced by both surface roughness and surface chemistry changes; the important contributor, however, was increased nanometer surface roughness. This claim is supported by the fact that cell number was enhanced on nano-structured compared to conventional PLGA and PU once chemistry changes were eliminated using casting techniques.