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In 1995, Edfors-Lilja and coworkers mapped the locus for the E. coli K88ab (F4ab) and K88ac (F4ac) intestinal receptor to pig chromosome 13 (SSC13). Using the same family material we have refined the map position to a region between the microsatellite markers Sw207 and Sw225. Primers from these markers were used to screen a pig BAC library and the positive clones were used for fluorescent in situ hybridization (FISH) analysis. The results of the FISH analysis helped to propose a candidate gene region in the SSC13q41→q44 interval. Shotgun sequencing of the FISH-mapped BAC clones revealed that the candidate region contains an evolutionary breakpoint between human and pig. In order to further characterise the rearrangements between SSC13 and human chromosome 3 (HSA3), detailed gene mapping of SSC13 was carried out. Based on this mapping data we have constructed a detailed comparative map between SSC13 and HSA3. Two candidate regions on human chromosome 3 have been identified that are likely to harbour the human homologue of the gene responsible for susceptibility towards E. coli F4ab/ac diarrhoea in pigs. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The porcine PER1 gene was mapped to chromosome 12q1.4→q1.5 using fluorescence in situ hybridisation. A polymorphic microsatellite marker (S0601) was isolated from a BAC clone shown to contain the PER1 gene. Linkage analysis assigned S0601 distal to ALOX12 on SSC12, providing further evidence for the conservation of synteny between HSA17 and SSC12. RT-PCR analysis demonstrated the expression of PER1 in all 11 tissues tested, consistent with the data from other mammalian species. Part of the PER1 gene was sequenced, homologous to exons 2–14 of the human gene and encoding the N-terminus of porcine PER1. The predicted amino acid sequence of the partial pig PER1 protein shares over 96% identity with its human orthologue. Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In the 1970s, several studies revealed the requirement for silicon in bone development, while bioactive silicate glasses simultaneously pioneered the current era of bioactive materials. Considerable research has subsequently focused on the chemistry and biological function of silicon in bone, demonstrating that the element has at least two separate effects in the extracellular matrix: (i) interacting with glycosaminoglycans and proteoglycans during their synthesis, and (ii) forming ionic substitutions in the crystal lattice structure of hydroxyapatite. In addition, the dissolution products of bioactive glass (predominantly silicic acids) have significant effects on the molecular biology of osteoblasts in vitro, regulating the expression of several genes including key osteoblastic markers, cell cycle regulators and extracellular matrix proteins. Researchers have sought to capitalize on these effects and have generated a diverse array of biomaterials, which include bioactive glasses, silicon-substituted hydroxyapatites and pure, porosified silicon, but all these materials share similarities in the mechanisms that result in their bioactivity. This review discusses the current data obtained from original research in biochemistry and biomaterials science supporting the role of silicon in bone, comparing both the biological function of the element and analysing the evolution of silicon-containing biomaterials., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The autonomic nervous system through its hypothalamic neuroendocrine control of puberty, skeletal growth and menarche contributes importantly to the pathogenesis of adolescent idiopathic scoliosis (AIS). Melatonin dysfunction detected in AIS subjects also involves the autonomic nervous system. The thoracospinal concept for the pathogenesis of right thoracic AIS in girls thought by some to result from dysfunction of the sympathetic nervous system (SNS), is supported by recent vascular and peripheral nerve studies. Lower body mass index (BMI).in girls with AIS is associated with decreased circulating leptin levels. Leptin, secreted by adipocytes, is a master hormone with many regulatory functions for growth and reproduction, including: 1) appetite repression, anorexigenic; 2) initiation of puberty in girls in a permissive action, and 3) in mice, longitudinal bone growth, chondrogenic and angiogenic, and in bone formation, antiosteogenic acting centrally through the SNS and possibly directly. In AIS girls, autonomic nervous system activity was reported to be higher than in controls. We suggest that in AIS susceptible girls, given adequate nutrition and energy stores, circulating leptin talks to the hypothalamus where dysfunction leads to an altered sensitivity to leptin resulting in increased SNS activity contributing with neuroendocrine mechanisms to: 1) earlier age at, and increased peak height velocity, 2) general skeletal overgrowth, 3) earlier skeletal maturation, 4) extra-spinal skeletal length asymmetries, including periapical ribs and ilia, 5) generalized osteopenia, and 6) lower BMI. The SNS-driven effects may also add adventitious changes to the spine including asymmetries complicating the neuroendocrine effects on adolescent spinal growth. In AIS pathogenesis, the leptin-SNS concept is complementary to our NOTOM escalator concept involving the somatic nervous system. Together these two concepts view AIS in girls as being initiated by a hypothalamic dysfunction of energy metabolism (bioenergetics) affecting skeletal growth in the trunk. Where, in susceptible girls, the postural mechanisms of the somatic nervous system fail to control the asymmetric spinal and/or rib growth changes in a rapidly enlarging adolescent spine; this failure becomes evident as mild back-shape shape asymmetry, or scoliosis. The environmentally-enhanced stature of normal subjects in the last 300 years, in girls susceptible to AIS, may have exaggerated any developmental dysharmony between the autonomic and somatic nervous systems being fought out in the spine and trunk of the girl - possibly making mild back-shape asymmetry, or scoliosis more prevalent today than hitherto.

Objectives: To assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability., Design: Prospective randomised controlled trial of calf muscle stimulation., Materials and Methods: Stable claudicants were randomised to receive either active chronic low frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one leg, 3 x 20 min per day for four weeks. Leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (ACR), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention., Results: Acute active muscle stimulation activated leucocytes less (28% increase) than a standard treadmill test (81% increase) and did not increase ACR. Chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70, P<0.05) while control treatment had no effect. Active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force., Conclusions: Chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.

When rolling adherent neutrophils are stimulated, they rapidly immobilize through activation of integrin CD11b/CD18, and then modulate attachment through this integrin to allow migration. We investigated links between cytoskeletal rearrangement and changes in function of integrin CD11b/CD18 in neutrophils stimulated with formyl peptide (fMLP). Neutrophils treated with the actin-polymerizing agent jasplakinolide became rolling adherent on monolayers of activated platelets, but could not use CD11b/CD18 to become immobilised when fMLP was perfused over them. If treated with jasplakinolide after fMLP, the cells stopped migrating but could not detach when fMLP was removed. Jasplakinolide did not inhibit changes in intracellular Ca(2+) seen after fMLP treatment, or inhibit neutrophil immobilisation induced by externally added Mn(2+). Thus cytoskeletal rearrangement was directly implicated in upregulation and, later, downregulation of CD11b/CD18 binding. Inhibition of RhoA with C3-transferase caused a dose-dependent reduction of initial rolling adhesion of neutrophils, and reduced the rate of migration after stimulation; however, neither the conversion of rolling to stationary adhesion, nor the ability of neutrophils to detach on removal of the stimulus, were inhibited. Thus, Rho may regulate actin polymerisation and motility in neutrophils, but did not appear to control integrin-mediated adhesion itself. Integrin binding may be promoted by disruption of links to the cytoskeleton, effected through depolymerisation of actin or cleavage of linking protein talin by calpain. Disruption of actin filaments with cytochalasin D did not, however, cause integrin-mediated immobilisation of rolling neutrophils. Although the calpain inhibitor calpeptin did inhibit the adhesion response to fMLP, this was only at doses where actin polymerisation was also ablated. We suggest that the cytoskeleton actively regulates binding conformation of CD11b/CD18 as well as its mobility in the membrane.

Seasonal infertility in sows is a problem in the pig industry characterized by delayed onset of puberty in summer and decreased farrowing rate resulting from silent oestrus and aborted pregnancy. Summer infertility is thought to be influenced by heat, sunburn and stress. However, the strongest contributory factor is photoperiod. The difference in seasonality between wild boar and commercial pig breeds suggests that there may be a genetic component to this trait. The maps and associated molecular tools emerging from the pig genome project have created opportunities to examine the genetic component of seasonal infertility. We are identifying and mapping genes that are likely to be involved in biological clock mechanisms and the melatonin pathways as candidate seasonality genes.

Previous studies have suggested that only a small proportion (< 15%) of comatose head-injured patients whose initial computerized tomography (CT) scan was normal or did not show a mass lesion, midline shift, or abnormal basal cisterns develop intracranial hypertension. The aim of the present study was to re-examine this finding against a background of more intensive monitoring and data acquisition. Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or less, whose admission CT scan did not show a mass lesion, midline shift, or effaced basal cisterns, underwent minute-to-minute recordings of arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) derived from blood pressure minus ICP. Intracranial hypertension (ICP > or = 20 mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients; in five cases the rise was pronounced in terms of both magnitude (ICP > or = 30 mm Hg) and duration. Reduced CPP (< or = 60 mm Hg lasting longer than 5 minutes) was recorded in five patients. Severely head-injured (comatose) patients whose initial CT scan is normal or does not show a mass lesion, midline shift, or abnormal cisterns nevertheless remain at substantial risk of developing significant secondary cerebral insults due to elevated ICP and reduced CPP. The authors recommend continuous ICP and blood pressure monitoring with derivation of CPP in all comatose head-injured patients.

Primary traumatic brain damage may be compounded by secondary pathophysiological insults that can occur soon after trauma, during transfer to hospital or subsequent treatment of the head-injured patient. The aim of this prospective study was to quantify the burden of a wide range of secondary insults occurring after head injury and to relate these to 12-month outcome. In 124 adult head-injured patients studied during intensive care using a computerized data collection system, < or = 14 clinically indicated physiological variables were measured minute-by-minute. Verified values falling outside threshold limits for > or = 5 min, as defined by the Edinburgh University Secondary Insult Grading scheme, were analysed by insult grade and duration. A greater incidence of secondary insults was detected than previous studies have indicated. Insults were found in 91% of patients and occurred in all severities of head trauma, at all ages, and at every level of Injury Severity Score (ISS). The cumulative durations were much greater than previously recorded although 85% of the total time was at the least severe grade. Short duration insults were common. In 71 patients, in whom 8 insults could be assessed (intracranial pressure, arterial hypo- and hypertension, cerebral perfusion pressure, hypoxemia, pyrexia, brady- and tachycardia), outcome at 12 months was analysed using logistic regression to determine the relative influence of age, admission Glasgow Coma Sumscore, ISS, pupil response on admission, and insult duration on both mortality and morbidity. The most significant predictors of mortality in this patient set were durations of hypotensive (p = .0064), pyrexic (p = .0137), and hypoxemic (p = .0244) insults. When good versus poor outcome was considered, hypotensive insults (p = .0118) and pupil response on admission (p = .0226) were significant.

This study was set up to test the reliability of the Glasgow Outcome Scale (GOS) when information was obtained from different sources. Eighty assessments were carried out on a group of 58 patients at three different time intervals up to 24 months post-injury. Each assessment consisted of three independently obtained GOS scores for each patient; (i) a score by a research psychologist after interview and neuropsychological testing of the patient; (ii) a score, obtained by post, by the patient's general practitioner (GP), and (iii) a score made by a research worker based on questionnaire information obtained from relatives by post. The agreement between the psychologist's score and that based on the relatives' information was high (r = 0.79 p = 0.001) whereas the correlation between the psychologist's score and that of the GP was low (r = 0.49 p = 0.001). The GPs tended to make overoptimistic assessments and this was most notable at 6 months post-injury when only 50% of the GPs' assessments agreed with those of the psychologist. We have shown that reliability of the GOS varies with the method of obtaining data. Ideally patients should be interviewed and tested by staff who have not been involved in the acute care of the patient. Failing this, information should be obtained from relatives of the patient and used by staff, trained in the use of the GOS, to assign a GOS score.