Genetic aspects of the organization of legumin genes in pea

We have compared physical and genetic maps of the region around the legJ gene in pea. In this vicinity there are four B-type legumin genes, arranged as two close pairs. The detection of a recombination event within this gene cluster allows the orientation of this group of genes within the surrounding linkage group to be determined. The relationship between physical and genetic distances in this region is discussed, as are the implications of this for relating physical and genetic maps elsewhere in the pea genome.

Quality aspects in service ecosystems : areas for exploitation and exploration

Service Science, Management, and Engineering (SSME) is a research area with significant relevance to research and practice. Networked systems of web services are a field of service science that enjoys growing interest from researchers. The complex and dynamic environment of these service ecosystems poses new requirements on quality management that are insufficiently addressed by current approaches that focus mainly on the technical aspects of quality. This focus is a severe limitation for the development of service networks because it neglects perceived service quality from the viewpoint of service consumers. In this paper we propose a reference model for quality management in service ecosystems. This reference model is linked in particular to innovation and new service development. Towards the end we propose premises for the implementation and outline a future research agenda.

Three-dimensional dose verification for clinical treatments of small intracranial tumours

Cancers of the brain and central nervous system account for 1.6% of new cancers and 1.8% of cancer deaths globally. The highest rates of all developed nations are observed in Australia and New Zealand. There are known complexities associated with dose measurement of very small radiation fields. Here, 3D dosimetric verification of treatments for small intracranial tumours using gel dosimetry was investigated.

Clinical use of objective measures of physical activity

With measurement of physical activity becoming more common in clinical practice, it is imperative that healthcare professionals become more knowledgeable about the different methods available to objectively measure physical activity behaviour. Objective measures do not rely on information provided by the patient, but instead measure and record the biomechanical or physiological consequences of performing physical activity, often in real time. As such, objective measures are not subject to the reporting bias or recall problems associated with self-report methods. The purpose of this article was to provide an overview of the different methods used to objectively measure physical activity in clinical practice. The review was delimited to heart rate monitoring, accelerometers and pedometers since their small size, low participant burden and relatively low cost make these objective measures appropriate for use in clinical practice settings. For each measure, strengths and weakness were discussed; and whenever possible, literature-based examples of implementation were provided.

Neck movement and muscle activity characteristics in female office workers with neck pain

Study Design Cross-sectional study. Objective To explore aspects of cervical musculoskeletal function in female office workers with neck pain. Summary of Background Data Evidence of physical characteristics that differentiate computer workers with and without neck pain is sparse. Patients with chronic neck pain demonstrate reduced motion and altered patterns of muscle control in the cervical flexor and upper trapezius (UT) muscles during specific tasks. Understanding cervical musculoskeletal function in office workers will better direct intervention and prevention strategies. Methods Measures included neck range of motion; superficial neck flexor muscle activity during a clinical test, the craniocerivcal flexion test; and a motor task, a unilateral muscle coordination task, to assess the activity of both the anterior and posterior neck muscles. Office workers with and without neck pain were formed into 3 groups based on their scores on the Neck Disability Index. Nonworking women without neck pain formed the control group. Surface electromyographic activity was recorded bilaterally from the sternocleidomastoid, anterior scalene (AS), cervical extensor (CE) and UT muscles. Results Workers with neck pain had reduced rotation range and increased activity of the superficial cervical flexors during the craniocervical flexion test. During the coordination task, workers with pain demonstrated greater activity in the CE muscles bilaterally. On completion of the task, the UT and dominant CE and AS muscles demonstrated an inability to relax in workers with pain. In general, there was a linear relationship between the workers’ self-reported levels of pain and disability and the movement and muscle changes. Conclusion These results are consistent with those found in other cervical musculoskeletal disorders and may represent an altered muscle recruitment strategy to stabilize the head and neck. An exercise program including motor reeducation may assist in the management of neck pain in office workers.

Oncogene-induced basement membrane invasiveness in human mammary epithelial cells

Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell lines in vitro and in vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-rasH, v-rasKi, v -mos, SV40T and c -myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determined in vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection with ras, despite similar ras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-rasH + SV40T and v -rasH + v -mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentinpositive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines. Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness.

Human breast cancer cell metastasis to long bone and soft organs of nude mice : a quantitative assay

Bone is a common metastatic site in human breast cancer (HBC). Since bone metastasis occurs very rarely from current spontaneous or experimental metastasis models of HBC cells in nude mice, an arterial seeding model involving the direct injection of the cells into the left ventricle has been developed to better understand the mechanisms involved in this process. We present here a sensitive polymerase chain reaction (PCR) method to detect and quantitate bone and soft organ metastasis in nude mice which have been intracardially inoculated with Lac Z transduced HBC cells. Amplification of genomically incorporated Lac Z sequences in MDA-MB-231-BAG HBC cells enables us to specifically detect these cells in mouse organs and bones. We have also created a competitive template to use as an internal standard in the PCR reactions, allowing us to better quantitate levels of HBC metastasis. The results of this PCR detection method correlate well with cell culture detection from alternate long bones from the same mice, and are more sensitive than gross Lac Z staining with X-gal or routine histology. Comparable qualitative results were obtained with PCR and culture in a titration experiment in which mice were inoculated with increasing numbers of cells, but PCR is more quantifiable, less time consuming, and less expensive. This assay can be employed to study the molecular and cellular aspects of bone metastasis, and could easily be used in conjunction with RT-PCR-based analyses of gene products which may be involved with HBC metastasis.

EMT and MET in carcinoma : clinical observations, regulatory pathways and new models

The articles collected here in this special edition Epithelial-Mesenchymal (EMT) and Mesenchymal-Epithelial Transitions (MET) in Cancer provide a snapshot of the very rapidly progressing cinemascope of the involvement of these transitions in carcinoma progression. Pubmed analysis of EMT and cancer shows an exponential increase in the last few years in the number of papers and reviews published under these terms (Fig. 1). The last few years have seen these articles appearing in high calibre journals including Nature, Nature Cell Biology, Cancer Cell, PNAS, JNCI, JCI, and Cell, signaling the acceptance and quality of work in this field.

Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA- MB-231 human breast cancer cells

We have previously reported that induction of MMP-2 activation by Concanavalin A (ConA) in MDA-MB-231 human breast cancer cells involves both transcriptional and post-transcriptional mechanisms, and that the continuous presence of ConA is required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995). In an effort to identify signal transduction pathways which may either contribute to or modulate this mechanism, we found that three different cAMP-inducing agents, cholera toxin (CT), forskolin (FSK), and 3- isobutyl-1-methylxanthine (IBMX) partially inhibited ConA-induced MT1-MMP expression and MMP-2 activation in MDA-MB-231 cells. Combinations of CT or FSK with IBMX exhibited additive effects on reduction of MT1-MMP mRNA expression and MMP-2 activation. Agents which increase cAMP levels appeared to target transcriptional aspects of ConA induction, reducing MT1-MMP mRNA and protein in parallel with the reduced MMP-2 activation. In the absence of ConA, down-regulation of constitutive production of MT1-MMP mRNA and protein was observed, indicating that cAMP acts independently of ConA. These observations may help to elucidate factors regulating MT1-MMP expression, which may be pivotal to the elaboration of invasive machinery on the cell surface.

Understanding negation and family history to improve clinical information retrieval

We present a study to understand the effect that negated terms (e.g., "no fever") and family history (e.g., "family history of diabetes") have on searching clinical records. Our analysis is aimed at devising the most effective means of handling negation and family history. In doing so, we explicitly represent a clinical record according to its different content types: negated, family history and normal content; the retrieval model weights each of these separately. Empirical evaluation shows that overall the presence of negation harms retrieval effectiveness while family history has little effect. We show negation is best handled by weighting negated content (rather than the common practise of removing or replacing it). However, we also show that many queries benefit from the inclusion of negated content and that negation is optimally handled on a per-query basis. Additional evaluation shows that adaptive handing of negated and family history content can have significant benefits.

Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Molecular aspects of tissue engineering in the dental field

Tissue engineering is a multidisciplinary field with the potential to replace tissues lost as a result of trauma, cancer surgery, or organ dysfunction. The successful production, integration, and maintenance of any tissue-engineered product are a result of numerous molecular interactions inside and outside the cell. We consider the essential elements for successful tissue engineering to be a matrix scaffold, space, cells, and vasculature, each of which has a significant and distinct molecular underpinning (Fig. 1). Our approach capitalizes on these elements. Originally developed in the rat, our chamber model (Fig. 2) involves the placement of an arteriovenous loop (the vascular supply) in a polycarbonate chamber (protected space) with the addition of cells and an extracellular matrix such as Matrigel or endogenous fibrin (34, 153, 246, 247). This model has also been extended to the rabbit and pig (J. Dolderer, M. Findlay, W. Morrison, manuscript in preparation), and has been modified for the mouse to grow adipose tissue and islet cells (33, 114, 122) (Fig. 3)...

An exploratory study for the development of emergency nurse practitioner specialist clinical practice standards

This thesis presents a mixed methods study to develop specialty specific clinical practice standards for Emergency Nurse Practitioners. This is the first time in Australia that Nurse Practitioners standards have been developed for a clinical specialty. These standards will guide educational preparation for the role and ongoing Continuous Professional Development for endorsed Emergency Nurse Practitioners.