Genetic diversity in farm animals--a review.

Domestication of livestock species and a long history of migrations, selection and adaptation have created an enormous variety of breeds. Conservation of these genetic resources relies on demographic characterization, recording of production environments and effective data management. In addition, molecular genetic studies allow a comparison of genetic diversity within and across breeds and a reconstruction of the history of breeds and ancestral populations. This has been summarized for cattle, yak, water buffalo, sheep, goats, camelids, pigs, horses, and chickens. Further progress is expected to benefit from advances in molecular technology.

Pelvic teratoma with extensive spinal involvement in a neonate: an important differential diagnosis.

A 6-week-old girl presented with an abdominal mass and spinal cord compression. Clinical and radiological features indicated a diagnosis of congenital neuroblastoma. Histology revealed a diagnosis of germ cell tumour after therapy for neuroblastoma had been commenced. This is, to the authors' knowledge, the first reported case of paediatric dumbbell retroperitoneal teratoma.

Antenatal ultrasound and magnetic resonance imaging in localizing the level of lesion in spina bifida and correlation with postnatal outcome.

OBJECTIVE: To compare prenatal ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of spina bifida with postnatal MRI/surgical findings and to study the postnatal outcome in relation to the level of lesion and head signs on antenatal imaging. METHODS: A retrospective study of babies referred to a tertiary neurosurgical unit with a diagnosis of spina bifida in the years 2000-2002 was performed. The levels of lesions and head signs diagnosed using antenatal ultrasonography and MRI were compared with postnatal MRI and operative findings. The levels of lesions and head signs diagnosed pre- and postnatally were used to study the correlation with neurological outcome at a mean follow-up period of 12 months. RESULTS: Twelve antenatally diagnosed and five postnatally diagnosed cases of spina bifida were seen. The level of lesion as identified by antenatal ultrasound correlated with that observed postnatally in 8/12 cases and the antenatal ultrasound diagnosis of ventriculomegaly was confirmed postnatally in all cases. The level of lesion as identified by antenatal MRI correlated with that observed postnatally in 4/8 cases (50%) and the antenatal MRI diagnosis of ventriculomegaly was confirmed postnatally in 5/8 (63%) cases. 12/17 babies were found to have residuals in the immediate postnatal urodynamic studies, of which 83% (n = 10) required intermittent catheterization of the bladder at 12 months of age. Low spinal lesions were associated with increased bladder morbidity when compared to high spinal lesions (8/10 vs. 4/7, P < 0.05) (odds ratio (OR) = 10.0; 95% CI, 1.05-95.01). The level of spinal lesion and the presence of ventriculomegaly did not have any statistically significant correlation with motor functions, morbidity and developmental milestones. CONCLUSIONS: Antenatal ultrasonography is a good tool in the diagnosis of spina bifida. We could not demonstrate any advantage of antenatal MRI over ultrasonography. There is better correlation of ultrasonography than MRI with postnatal MRI/operative findings in terms of level of lesion and head signs. Low spinal lesions appear to be associated with increased bladder morbidity.

Can CT determine the site of traumatic osteochondral defects in the paediatric knee?

Currently the ability of pre-operative CT imaging to determine the origin of traumatic osteochondral lesions (OCL) in the knee in children is yet to be established. The surgical approach to the knee will to some extent be determined by the origin of the lesion. It is important to directly determine the site of the lesion from pre-operative scanning both to facilitate surgery, to have a better cosmetic result for the patient and have a quicker rehabilitation period. In a tertiary referral centre, from May 2004 to April 2005, eight patients were diagnosed as having an OCL. The initial reporting was done by either a senior registrar or consultant paediatric radiologist. Those children that had an OCL underwent an arthroscopy or definitive open surgery. The exact site of the lesion was then determined and recorded in the operative notes. All the original pre-operative CT scans were given to a senior paediatric radiologist. The consultant on this occasion had no access to operative findings, or original CT reports. CTs reported by the paediatric radiology department are only able to correctly identify the site of origin of the OCL 50% of the time. Recent MR scanning techniques have improved the visualization of OCL. We authors therefore feel that in the future MRI should be used to assess the paediatric knee when an acute OCL is suspected.

Bronchopulmonary foregut malformations: embryology, radiology and quandary.

Bronchopulmonary foregut malformations (BPFM) are a heterogeneous group of pulmonary developmental anomalies that present at varying ages and with overlapping symptoms, signs and radiology. This article discusses the embryology of these lesions with reference to possible common origins and the link between aetiology and radiological appearance. The radiology of each lesion, both antenatally and postnatally, is described and illustrated. A number of quandaries exist in the prediction of prognosis and subsequent treatment of BPFM. We discuss the radiological features that may help to elucidate an individual prognosis and aid in the planning of treatment. The treatment options available for BPFM are briefly discussed. Finally, the link between BPFM, in particular cystic adenomatoid malformations and malignancy, is discussed. We aim to provide a comprehensive overview of the embryology, radiology, prognosis and treatment highlighting contentious issues of BPFM.

Transendothelial migration confers a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions.

The clearance of activated T lymphocytes by apoptosis is an essential component in the resolution of the immune response; however, certain signals received within inflamed tissue may result in the persistence of activated T cells. Our previous work has shown that, when compared with resting cells, effector cells migrate more efficiently across endothelium, thus such cells may be selectively recruited to sites of inflammation. We hypothesized that transmigration of T cells across endothelium might influence cell survival. We have generated T cell lines by culturing in IL-2 following PHA activation. These T cell lines die rapidly by apoptosis when deprived of IL-2 (53.7 +/- 4.0% survival after 24 h). In contrast, cells that have migrated across human umbilical vein endothelial cells (HUVEC) survived significantly better than control cells (80.3 +/- 3.6%, n= 18, P<0.001). Endothelial cell conditioned medium was also able to reduce apoptosis, but this effect was small when compared with the protective effect of transmigration. Culture of T lymphocytes on fibronectin, or RGD peptides, or in suspension with a range of chemokines active on T cells, including RANTES and lymphotactin had no effect on survival. In contrast, blocking LFA-l/ICAM-l interactions reduced the protective effect of transmigration (42.3 +/- 6.7% reduction). Culture of activated T cells on immobilized ICAM-l alone also increased survival. These results indicate that signals received by activated T cells during extravasation can influence their subsequent survival within tissue, and implicates the involvement of LF A-l/ICAM-l interactions.

Ultrasound guidance allows accurate needle placement and aspiration from small joints in patients with early inflammatory arthritis.

OBJECTIVES: To compare the accuracy of palpation-guided and high frequency ultrasound-guided needle placement in small joints and to develop a technique to obtain synovial fluid from these joints for diagnosis and research. METHODS: The accuracy of needle placement during palpation-guided proximal interphalangeal (PIP) or metacarpophalangeal (MCP) joint injection was assessed. This was compared with the accuracy of ultrasound-guided needle placement. A joint lavage technique was developed to obtain synovial fluid from these joints. RESULTS: Needle positioning was intra-articular in 59% of palpation-guided injections (6/12 PIP and 4/5 MCP joints). No fluid could be aspirated prior to injection. With ultrasound guidance, initial needle placement was intra-articular in 96% of cases (24/26 PIP and 27/27 MCP joints). Synovial fluid cells were lavaged from 63% of joints (19/25 PIP and 14/27 MCP joints). In only one case was a large effusion seen and this was aspirated directly. CONCLUSIONS: The use of high frequency ultrasound to guide needle placement within a small joint allows for significantly greater accuracy than a palpation-guided approach. When followed by lavage, synovial fluid cells and diluted synovial fluid can be obtained from the majority of small joints. This has important clinical and research implications.

Extracranial vascular malformation: value of antenatal and postnatal MRI in management.

We report a case where fetal MRI using a low-field-strength magnet (0.5 T) accurately confirmed a large extracranial vascular malformation, which was suspected on antenatal US. Fetal MRI enabled better counselling of the parents and allowed suitable plans to be made regarding method of delivery and early management of the neonate. To our knowledge this is the first case of an extracranial vascular malformation imaged using fetal MRI.

Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics.

Using HLA class I-viral epitope tetramers to monitor herpes virus-specific CD8(+) T cell responses in humans, we have shown that a significant fraction of responding cells revert from a CD45RO(+) to a CD45RA(+) state after priming. All tetramer-binding CD45RA(+) cells, regardless of epitope specificity, expressed a phenotype LFA-1(high)CCR7(low) that was stable for at least 10 years in infectious mononucleosis patients and indefinitely in asymptomatic carriers. CD8(+)CD45RA(+)LFA-1(high) cells were not present in cord blood but in adults account for up to 50% of CD8(+)CD45RA(+) cells. These CD45RA(+)LFA-1(high) cells have significantly shorter telomeres than CD45RA(+)LFA-1(low) cells, suggesting that the latter represent a naive population, while the former are memory cells. CD45RA(+) memory cells are a stable population of noncycling cells, but on stimulation they are potent producers of IFN-gamma, while naive CD8(+) cells produce only IL-2. The chemokine receptor profile and migratory potential of CD45RA(+) memory cells is very similar to CD45RO(+) cells but different to naive CD8 cells. In accord with this, CD45RA(+) memory cells were significantly underrepresented in lymph nodes, but account for virtually all CD8(+)CD45RA(+) T cells in peripheral tissues of the same individuals.

Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation.

Fibroblasts are important sentinel cells in the immune system and, here, it is proposed that these cells play a critical role in the switch from acute inflammation to adaptive immunity and tissue repair. It is suggested that chronic inflammation occurs because of disordered fibroblast behaviour in which failure to switch off their inflammatory programme leads to the inappropriate survival and retention of leukocytes within inflamed tissue.

Prenatal diagnosis of suprasellar arachnoid cyst and postnatal endoscopic treatment.

Arachnoid cysts are benign developmental anomalies that occur in the cerebrospinal axis in relation to the arachnoid membrane. An antenatal ultrasound scan first raises the suspicion of arachnoid cysts, but misdiagnoses have been reported. Confirmatory antenatal magnetic resonance imaging (MRI) is very useful to delineate anatomical detail and help in correct diagnosis. This helps proper counselling and treatment planning. Controversy also surrounds the surgical management, in terms of both the indications and the procedures employed. We report the successful endoscopic treatment, in a neonate, of an arachnoid cyst diagnosed by antenatal ultrasound and MRI. In this case accurate diagnosis and detailed assessment led to objective counselling and helped to optimise neonatal management.

Type 1 IFN maintains the survival of anergic CD4+ T cells.

Anergic T cells have immunoregulatory activity and can survive for extended periods in vivo. It is unclear how anergic T cells escape from deletion, because both anergy and apoptosis can occur after TCR ligation. Stimulation of human CD4+ T cell clones reactive to influenza hemagglutinin peptides can occur in the absence of APCs when MHC class II-expressing, activated T cells present peptide to each other. This T:T peptide presentation can induce CD95-mediated apoptosis, while the cells that do not die are anergic. We found that the death after peptide or anti-CD3 treatment of a panel of CD4+ T cell clones is blocked by IFN-beta secreted by fibroblasts and also by IFN-alpha. This increases cell recovery after stimulation, which is not due to T cell proliferation. This mechanism for apoptosis inhibition rapidly stops protein kinase C-delta translocation from the cytoplasm to the nucleus, which is an early event in the death process. A central observation was that CD4+ T cells that are rescued from apoptosis after T:T presentation of peptide by IFN-alphabeta remain profoundly anergic to rechallenge with Ag-pulsed APCs. However, anergized cells retain the ability to respond to IL-2, showing that they are nonresponsive but functional. The prevention of peptide-induced apoptosis in activated T cells by IFN-alphabeta is a novel mechanism that may enable the survival and maintenance of anergic T cell populations after TCR engagement. This has important implications for the persistence of anergic T cells with the potential for immunoregulatory function in vivo.

Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium.

Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. We show that synovial T cells, which are primed CD45RO+CD45RBdull cells and consequently not expected to express constitutive chemokine receptors, have high levels of the chemokine receptor CXCR4. Sustained expression of CXCR4 was maintained on synovial T cells by specific factors present within the synovial microenvironment. Extensive screening revealed that TGF-beta isoforms induce the expression of CXCR4 on CD4 T cells in vitro. Depletion studies using synovial fluid confirmed an important role for TGF-beta1 in the induction of CXCR4 expression in vivo. The only known ligand for CXCR4 is SDF-1. We found SDF-1 on synovial endothelial cells and showed that SDF-1 was able to induce strong integrin-mediated adhesion of synovial fluid T cells to fibronectin and ICAM-1, confirming that CXCR4 expressed on synovial T cells was functional. These results suggest that the persistent induction of CXCR4 on synovial T cells by TGF-beta1 leads to their active, SDF-1-mediated retention in a perivascular distribution within the rheumatoid synovium.

The incidence and significance of testicular microlithiasis in a subfertile population.

The objective of this study was to assess the frequency of testicular microlithiasis (TM) in infertile men who underwent testicular ultrasound and to determine any causative or associated factors. The case notes of 159 consecutive patients who were referred for testicular ultrasound in the investigation of male factor infertility were reviewed. Microcalcification was found in 10 cases (6.2%). This was unilateral in all cases and six patients had clinical evidence of a varicocele. Five cases had minimal calcification and five had marked TM. On patient had a past history of testicular maldescent and another of testicular torsion. Sperm function (as assessed by sperm count, motility and the sperm migration test) was variable within the 10 patients and there was no correlation with hormone profiles or testicular size. There was a statistical difference between a number of investigations in those patients with minimal degrees of calcification and those with TM (sperm migration test (SMT), namely sperm migration and sperm motility (p < 0.05, Mann-Whitney U test)). The results showed a higher than expected incidence of TM. Patients with marked TM seemed to have poorer sperm function than those with minimal calcification. There was a high incidence of co-existing pathology, for instance scrotal varicocele and cryptorchidism, although the numbers in this study were small and further studies need to be carried out to determine the exact nature and significance of this condition.

High cell density provides potent survival signals for resting T-cells.

Activated T-cells are susceptible to apoptosis through two particularly important pathways: ligation of CD95 (Fas/Apo-1) or cytokine deprivation. Resting T-cells have until recently been considered to be relatively resistant to apoptosis. In this report we show that resting T-cells die rapidly by apoptosis when deprived of serum or cell contact. Primed CD45RO+ cells were more susceptible than naive CD45RA+ cells, consistent with their relative expression of Bcl-2. CD4+, CD8+ and gammadelta T-cells were equally prone to apoptosis under all studied conditions. A linear relationship between cell survival and serum concentration was observed for cells cultured between 0.5-2x10(6)/ml. T-cells cultured at low density died even in high concentrations of serum. However, resting T-cells cultured at high cell density (4x10(6)/ml) survived for extended periods in the absence of serum or other survival factors. This effect was mediated by the production of soluble factors and independent of integrin mediated signals. These results suggest that T-cells at sites of high density such as the lymph node paracortex are independent of external survival factors, while those trafficking through the peripheral circulation are highly dependent on serum derived factors for survival.

Persistent acquired lobar overinflation complicating bronchopulmonary dysplasia.

UNLABELLED: Persistent acquired lobar overinflation (PALO) may complicate bronchopulmonary dysplasia (BPD). From infants admitted to the regional neonatal intensive care unit or who had been followed up at the chronic lung disease clinic in Liverpool over a 6.5-year period, 11 children with BPD and PALO were identified and details of their neonatal and subsequent outcome obtained. Their median gestational age was 29 weeks (range 24-33) and median birth weight was 1317 g (range 676-1968 g). All had received ventilatory support for severe neonatal respiratory distress syndrome for a median of 26 days (range 5-86). The median age the acquired lobar overinflation was detected was 82 days (range 45424 days). Nine patients required continued neonatal or paediatric intensive care re-admission for deteriorating respiratory function. Six children have subsequently died at a median age of 9.5 months (range 6.5-20). Five patients underwent bronchoscopy, four suggesting the presence of bronchomalacia. Three patients had ventilation-perfusion scans all showing that the overinflated lobe had no mismatch defect unlike other areas of the lung. CONCLUSION: The place of specific therapies for persistent acquired lobar overinflation is unclear. Surgery to remove the overinflated lobe in such cases may be inappropriate and the outcome of this complication of bronchopulmonary dysplasia appears to be poor.