The B subunit of coagulation factor XIII is linked to renin and the Duffy blood group to α-spectrin on human chromosome 1

Family linkage studies were used to detect two linkage relationships on human chromosome 1. The B subunit of coagulation factor XIII showed significant linkage to renin with a maximum lod score of 5.071 at a distance of 10 cM. Significant linkage was also shown between the Duffy blood group and α-spectrin with linkage results giving a combined lod score of 3.194 at 5 cM.

Regional chromosomal assignment of human renin gene to 1q12→qter and use in linkage studies in Charcot-Marie-Tooth disease

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12 → qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (λ HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 ± 1.6 weeks). The infants were fed breast milk with formula supplements (n=8) or formula alone (n=8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 ± 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 ± 0.4 μg/l) and preterm infants (1.8 ± 0.2 μg/l) was significantly below values reported for older children (10.5 ± 0.9 μg/l; p < 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p < 0.001). At birth, serum trypsinogen for preterm (16.8 ± 1.3 μg/l) and term infants (23.3 ± 1.9 μg/l) were below those for older children (31.4 ± 3.7 μg/l; p < 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.

Investigating the potential value of individual parameters of histological grading systems in a sheep model of cartilage damage : the modified Mankin method

A total histological grade does not necessarily distinguish between different manifestations of cartilage damage or degeneration. An accurate and reliable histological assessment method is required to separate normal and pathological tissue within a joint during treatment of degenerative joint conditions and to sub-classify the latter in meaningful ways. The Modified Mankin method may be adaptable for this purpose. We investigated how much detail may be lost by assigning one composite score/grade to represent different degenerative components of the osteoarthritic condition. We used four ovine injury models (sham surgery, anterior cruciate ligament/medial collateral ligament instability, simulated anatomic anterior cruciate ligament reconstruction and meniscal removal) to induce different degrees and potentially 'types' (mechanisms) of osteoarthritis. Articular cartilage was systematically harvested, prepared for histological examination and graded in a blinded fashion using a Modified Mankin grading method. Results showed that the possible permutations of cartilage damage were significant and far more varied than the current intended use that histological grading systems allow. Of 1352 cartilage specimens graded, 234 different manifestations of potential histological damage were observed across 23 potential individual grades of the Modified Mankin grading method. The results presented here show that current composite histological grading may contain additional information that could potentially discern different stages or mechanisms of cartilage damage and degeneration in a sheep model. This approach may be applicable to other grading systems.

Morphology of osteocyte cells in normal and hyper-gravity

Osteocyte cells are the most abundant cells in human bone tissue. Due to their unique morphology and location, osteocyte cells are thought to act as regulators in the bone remodelling process, and are believed to play an important role in astronauts’ bone mass loss after long-term space missions. There is increasing evidence showing that an osteocyte’s functions are highly affected by its morphology. However, changes in an osteocyte’s morphology under an altered gravity environment are still not well documented. Several in vitro studies have been recently conducted to investigate the morphological response of osteocyte cells to the microgravity environment, where osteocyte cells were cultured on a two-dimensional flat surface for at least 24 hours before microgravity experiments. Morphology changes of osteocyte cells in microgravity were then studied by comparing the cell area to 1g control cells. However, osteocyte cells found in vivo are with a more 3D morphology, and both cell body and dendritic processes are found sensitive to mechanical loadings. A round shape osteocyte’s cells support a less stiff cytoskeleton and are more sensitive to mechanical stimulations compared with flat cellular morphology. Thus, the relative flat and spread shape of isolated osteocytes in 2D culture may greatly hamper their sensitivity to a mechanical stimulus, and the lack of knowledge on the osteocyte’s morphological characteristics in culture may lead to subjective and noncomprehensive conclusions of how altered gravity impacts on an osteocyte’s morphology. Through this work empirical models were developed to quantitatively predicate the changes of morphology in osteocyte cell lines (MLO-Y4) in culture, and the response of osteocyte cells, which are relatively round in shape, to hyper-gravity stimulation has also been investigated. The morphology changes of MLO-Y4 cells in culture were quantified by measuring cell area and three dimensionless shape features including aspect ratio, circularity and solidity by using widely accepted image analysis software (ImageJTM). MLO-Y4 cells were cultured at low density (5×103 per well) and the changes in morphology were recorded over 10 hours. Based on the data obtained from the imaging analysis, empirical models were developed using the non-linear regression method. The developed empirical models accurately predict the morphology of MLO-Y4 cells for different culture times and can, therefore, be used as a reference model for analysing MLO-Y4 cell morphology changes within various biological/mechanical studies, as necessary. The morphological response of MLO-Y4 cells with a relatively round morphology to hyper-gravity environment has been investigated using a centrifuge. After 2 hours culture, MLO-Y4 cells were exposed to 20g for 30mins. Changes in the morphology of MLO-Y4 cells are quantitatively analysed by measuring the average value of cell area and dimensionless shape factors such as aspect ratio, solidity and circularity. In this study, no significant morphology changes were detected in MLO-Y4 cells under a hyper-gravity environment (20g for 30 mins) compared with 1g control cells.

Beyond normal competencies : understanding organisation designs to develop and sustain IT-related capabilities

It is apparent that IT resources are important for organisations. It is also clear that organisations unique competencies, their IT-related capabilities, leverage the IT resources uniquely to create and sustain competitive advantage. However, IT resources are dynamic, and evolve at an exponential rate. This means that organisations will need to sustain their competencies to leverage opportunities offered by new IT resources. Research on ways to sustain IT-related capabilities is limited and a deeper understanding of this situation is important. Amongst other factors, a possible reason for this lack of progress in this area could be due to the lack of validated measurement items of the theoretical constructs to conduct such studies. We suggest an environment in which organisations could build new and sustain their existing IT-related capabilities. We then report on the development of valid and reliable measures for this environment. The validated measures would be useful in extending our understanding on how firms could sustain their IT-related capabilities. This effort will provide a deeper understanding of how firms can secure sustainable IT-related business value from their acquired IT resources.

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients : the European Early Lung Cancer Project

Lung cancer is the most important cause of cancer-related mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification. Other determinants of tumour behaviour that predict disease outcome, such as molecular markers, may improve decision-making. Activation of the gene encoding human telomerase reverse transcriptase (hTERT) is implicated in the pathogenesis of lung cancer, and consequently detection of hTERT mRNA might have prognostic value for patients with early stage lung cancer. A cohort of patients who underwent a complete resection for early stage lung cancer was recruited as part of the European Early Lung Cancer (EUELC) project. In 166 patients expression of hTERT mRNA was determined in tumour tissue by quantitative real-time RT-PCR and related to that of a house-keeping gene (PBGD). Of a subgroup of 130 patients tumour-distant normal tissue was additionally available for hTERT mRNA analysis. The correlation between hTERT levels of surgical samples and disease-free survival was determined using a Fine and Gray hazard model. Although hTERT mRNA positivity in tumour tissue was significantly associated with clinical stage (Fisher's exact test p=0.016), neither hTERT mRNA detectability nor hTERT mRNA levels in tumour tissue were associated with clinical outcome. Conversely, hTERT positivity in adjacent normal samples was associated with progressive disease, 28% of patients with progressive disease versus 7.5% of disease-free patients had detectable hTERT mRNA in normal tissue [adjusted HR: 3.60 (1.64-7.94), p=0.0015]. hTERT mRNA level in tumour tissue has no prognostic value for patients with early stage lung cancer. However, detection of hTERT mRNA expression in tumour-distant normal lung tissue may indicate an increased risk of progressive disease.

Prognostic value of biochemical liver parameters in neonatal sepsis-associated cholestasis

Aims The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis. Methods: A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome. Results: The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT. Conclusion: Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis

Mechanical analysis of foot plantar fascia during normal walking condition

Foot plantar fascia is an important foot tissue in stabilizing the longitudinal arch of human foot. Direct measurement to monitor the mechanical situation of plantar fascia at human locomotion is difficult. The purpose of this study was to construct a three-dimensional finite element model of the foot to calculate the internal stress/strain value of plantar fascia during different stage of gait. The simulated stress distribution of plantar fascia was the lowest at heel-strike, which concentrated on the medial side of calcaneal tubercle. The peak stress of plantar fascia was appeared at push-off, and the value is more than 5 times of the heel-strike position. Current FE model was able to explore the plantar fascia tension trend at the main sub-phases of foot. More detailed fascia model and intrinsic muscle forces could be developed in the further study.