Imaging of the aortic valve with MRI and CT angiography.

The aortic valve may be affected by a wide range of congenital and acquired diseases. Echocardiography is the main non-invasive imaging technique for assessing patho-anatomical alterations of the aortic valve and adjacent structures and in many cases is sufficient to establish a diagnosis and/or guide treatment decisions. Recent technological advances in magnetic resonance imaging (MRI) and multidetector computed tomography (MDCT) have enabled these techniques to play a complimentary role in certain clinical scenarios and as such can be useful problem-solving tools. Radiologists should be familiar with the indications, advantages, and limitations of MRI and MDCT in order to advise and direct an appropriate imaging strategy depending upon the clinical scenario. This article reviews the role of MRI and MDCT angiography for assessment of the aortic valve including relevant anatomy, scan acquisition protocols, and post-processing methods. An approach to interpretation and the key imaging features of commonly encountered aortic valvular diseases are discussed.

The right scan, for the right patient, at the right time: the reorganization of major trauma service provision in England and its implications for radiologists.

Major trauma services in England are currently undergoing a radical overhaul with the formation of regional trauma networks and designated major trauma centres (MTCs). Radiology is scheduled to play a key role within major trauma care both in terms of 24/7 access to whole body computed tomography (WBCT) and interventional radiology (IR) services, as well as providing immediate expert imaging guidance to the trauma team. This review examines the rationale behind trauma networks, as well as drawing attention to the new Royal College of Radiologists' standards for major trauma imaging. It attempts to address radiologists' understandable concerns about the inappropriate use of WBCT, radiation dose, and intravenous contrast medium risks. Reporting whole-body CT for trauma patients is difficult, covering multiple body regions, with great pressure to provide a rapid and accurate report to the trauma team. The benefits of standardized reports, dual-radiologist reporting, and the use of organ injury severity grading are explored to aid succinct communication of findings and further guide patient management.

Inferior vena cava filters: what radiologists need to know.

Inferior vena cava (IVC) filters are a controversial mechanical adjunct in the prevention of pulmonary embolism, the most serious result of venous thromboembolism. Despite modern IVC filters being in clinical use for more than 45 years, there is still uncertainty amongst many radiologists about the indications for IVC filter placement and their removal, particularly the more recent prophylactic use in patients without confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE). Recently published guidelines on filter use from the National Institute of Health and Clinical Excellence (NICE) and other professional bodies are discussed. The vast majority of IVC filters in the UK are inserted by interventional radiologists, so radiologists may be the first point of contact for information requested by other clinicians. The increasing use of filters means that radiologists will encounter filters increasingly often during abdominal cross-sectional imaging. Awareness of common filter-related complications, such as tilting, thrombosis, and caval perforation, is useful to reassure or alert other clinicians. The potential role of filters in upper extremity DVT and requirement for concomitant anticoagulation is discussed.

Interleukin-12 restores dendritic cell function and cell-mediated immunity in retrovirus-infected mice.

The effects of IL-12 treatment on the defects in DC function and on the reduced cell-mediated immunity induced in mice infected with Rauscher leukemia virus (RLV) were studied. DC from RLV-infected mice failed to stimulate significant allogeneic T cell proliferation but T cells from RLV-infected mice showed normal responses to allogeneic DC. In RLV-infected mice treatment with 5 doses of 100 or 300 ng IL-12 around the time of infection resulted in DC that stimulated normal T cell proliferation. Treatment of mice with 300 ng IL-12 but not 100 ng reduced T cell responses. RLV-infected mice showed reduced delayed hypersensitivity to a contact sensitizer. Infected animals receiving the low dose of IL-12 which allowed normal DC and T cell function gave normal delayed hypersensitivity reactions; IL-12 thus resulted in both normal T cell stimulation by DC and cell-mediated immunity. A failure of T cell stimulation by DC is associated with immunosuppression in retrovirus infection and the enhanced capacity of DC to stimulate T cells after IL-12 treatment may be beneficial.

Measurement of the rate of myelination using a fluorescent analogue of ceramide.

Fluorescence digital imaging microscopy was used to investigate the process of myelin formation by Schwann cells in neuronal cocultures. The uptake of the fluorescent ceramide analogue N-[5-(5,7-dimethyl BODIPY)-1-pentanoyl]D-erythro-sphingosine (C5-DMB-ceramide) and its return to the plasma membrane as the corresponding fluorescent sphingomyelin and galactocerebroside analogues were measured. Through observation of this process it was possible to determine the rate of lipid synthesis in myelin internodes. The highest rate of synthesis of fluorescent sphingomyelin and galactocerebroside analogues was observed between days 3 and 7 after induction of myelination. This rate was approximately 5-fold greater than the steady-state rate of synthesis in fully myelinated internodes and 10-fold higher than the rate observed prior to myelination. The internode diameter increased during the first 3 days of myelination, but this was followed by a reduction in diameter and then an increase until the myelin sheath formation was completed. Internodes were found to be heterogeneous in terms of lipid distribution, with fluorescence intensities ranging 5-fold in myelinating cultures. Additionally, the rate of lipid transport along the internode was slow since there was a quicker increase in fluorescence intensity near the cell body of the Schwann cell than near the nodes of Ranvier. The results show that fluorescence digital imaging microscopy can be used to study the process of myelin formation and to determine the rate of formation, lipid transport, and heterogeneity of the myelin membrane.

Mechanism for dendritic cell dysfunction in retroviral infection of mice.

Dendritic cells (DC) from mice infected with the murine retrovirus Rauscher leukaemia virus (RLV) are poor stimulators of allogeneic and syngeneic T cells and express lower, but still significant, levels of MHC class II. In this paper we further investigated the mechanism of the dysfunction of DC. DC from infected animals did not cause anergy of T cells during coculture for 3 or 6 days. They did not release a substantial amount of soluble factors which could suppress T cell responses. The low T cell responses on stimulation using RLV-infected DC could be overcome by the addition of control DC. Pretreatment of these control DC with monoclonal antibody against MHC class II molecules completely blocked their ability to restore stimulation of T cells in the presence of infected DC. However, antibody against MHC class I or mismatched MHC class II molecules did not prevent restoration of function. The reduced labeling of surface MHC class II molecules previously reported was shown to reflect a loss in total class II molecules within the cells; MHC class I levels were unaltered by exposure to the virus. In DC from RLV-infected mice biosynthesis of MHC class II was decreased by around 50% at the transcriptional level in comparison with beta-actin. Thus, the down-regulation of surface class II molecules observed in DC following RLV infection is a consequence of a specific block in its biosynthesis and the failure of DC to stimulate T cells may be a direct consequence of the reduced class II levels. Since reduced stimulation by DC is also seen in HIV-1 infection in humans we speculate that a similar mechanism might operate in retroviral infection in man.

Murine retrovirus induces defects in the function of dendritic cells at early stages of infection.

The infection and function of lymph node dendritic cells (DC) were analyzed at different time points of Rauscher leukemia virus infection in mice (3, 7, 14, and 21 days). Infection of DC was apparent after 3 days and significant infection (1-10% of the DC population) was documented after 7 days. DC from infected mice as early as 3 days postinfection had a reduced ability to stimulate allogeneic normal T cells in the mixed lymphocyte reaction. T cells did become infected during the coculture but block of cross-infection of T cells by zidovudine did not abolish the inhibitory effect. Other DC-dependent responses were also reduced on infection including DC-stimulated responses to influenza virus. ConA and PMA induced an increase in [Ca2+]i level in DC from control mice. A low baseline level of [Ca2+]i in DC from infected mice and reduced calcium mobilization upon ConA stimulation was found at all periods of infection. Ultraviolet-inactivated Rauscher leukemia virus failed to provoke significant changes in DC function in vivo. Six or 7 days after RLV infection DC expressed lower levels of Iad but not H2Dd molecules in parallel with lower expression of some adhesion molecules (CD18, CD54, CD44). No differences in expression of B7 surface antigen between control and infected mice were obtained. We did not find any evidence for the induction of apoptosis of naive syngeneic or allogeneic T cells by infected dendritic cells. The changes in DC function may have implications for the pathogenesis of retroviral infections including HIV infection.

Retrovirus-induced immunosuppression via blocking of dendritic cell migration and down-regulation of adhesion molecules.

Dendritic cells (DC) within tissues may acquire and process antigens, carry them into lymph nodes and cluster and activate T cells. The ability of DC to acquire antigen and to migrate to lymph nodes was estimated during murine retroviral infection caused by Rauscher leukaemia virus (RLV). A novel mechanism of inducing immunodeficiency has now been identified. In mice infected with RLV, DC failed to migrate into lymph nodes following exposure of the skin to the contact sensitizer, fluorescein isothiocyanate. RLV infection of a proportion of DC both in skin and lymph nodes, shown by semi-quantitative polymerase chain reaction (PCR) and down-regulation of expression of adhesion molecules (CD54 and CD44) on the surface of Langerhans' cells, may contribute to the described phenomenon. A failure of DC migration could be an important immunosuppressive mechanism of RLV infection in mice and we speculate on a similar role for DC in human immunodeficiency virus-1 (HIV-1) infection in humans.

Effects of murine leukemia viruses on the function of dendritic cells.

In asymptomatic human immunodeficiency virus-1 infection T cells respond normally to allogeneic dendritic cells (DC), but DC show reduced stimulatory capacity. By contrast in HTLV-1 infection no significant changes in allogeneic stimulation were seen but DC-stimulated activity of autologous T cells. In seeking animal models relevant to these diseases the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendritic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stimulate allogeneic T cells from healthy animals. MLV at the same concentration did not significantly affect the ability of DC to stimulate allogeneic T cells, but provoked considerable enhancement of the low level stimulation by DC in the syngeneic system. Similar results were obtained following in vivo exposure to viruses. Two pieces of evidence suggested that these effects were due to impairment of DC function and were not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with untreated allogeneic DC caused no significant alteration in T cell activity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultured in the presence of zidovudine. Treatment of DC by RLV caused a decrease of cluster formation with allogeneic T cells. No statistically significant influence of MLV was observed on cluster formation after 3-h of incubation in the allogeneic system. However, after 18-h incubation MLV-treated DC formed fewer clusters with T cells than untreated DC. At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA-1 receptor expression on the DC surface in mice infected by RLV. MLV induced no significant changes. These mouse retroviruses can therefore cause changes in DC function similar to those already reported using human retroviruses and may provide models for studying their effects.

Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine.

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.

Factors affecting responses to murine oncogenic viral infections.

Silica specifically kills macrophages in vitro, and in vivo has been used as a method of determining the possible immunological or other roles of macrophages in a number of viral infections. In experiments reported here, injection of 30 or 50 mg silica i.p. increased the severity of the oncogenic effects of the murine sarcoma virus (MSV) and Friend virus (FV) in BALB/c mice. Unlike Herpes simplex and Coxsackie B-3 infections, however, passive transfer of adult macrophages to suckling mice did not protect the latter against MSV. In mice injected with silica, histological evidence of the compensatory proliferation of macrophages suggests that precursors of these cells may act as target cells for the virus and that this may override any immunosuppressive response effected by the silica. In addition, there was a considerable enhancing effect on the erythroproliferative response to both MSV and FV by injection of saline 5 h before the virus, and indeed to FV after only a simple abdominal needle puncture. We attributed this to the lymphopenic immunodepressive effects of stress, and our data may explain previously published findings of augmented oncogenic responses in mice after "normal" serum injections. Newborn BALB/c (FV-1b) mice were susceptible to N-tropic FV, but developed resistance by 29 days of age. Antithymocyte serum (ATS) but not silica injections or adult thymectomy ablated this resistance. C57BL (FV-2r) mice were completely resistant to FV; however, those receiving FV and ATS developed late-onset leukaemia histologically characteristic of that produced by the helper component of the FV complex.

Absence of ecotropic or recombinant murine leukaemia virus in preleukaemic and leukaemic X-irradiated NZB mice.

NZB mice X-irradiated with a single dose of 630 R when they were 1-month old developed a high incidence of histologically defined lymphocytic leukaemia 8--25 weeks later. We have screened for murine leukaemia viruses (MuLV) in the lymphoid tissues of 8 of these leukaemic mice, and in 8 "preleukaemic", apparently healthy NZBs killed 1 month post irradiation. Xenotropic, but not ecotropic or recombinant MuLV, was detected by in vitro co-cultivation of bone marrow, spleen and thymus with selectively permissive cell lines, followed by the immunofluorescence test for MuLV gs antigen, and the XC test. Our results are not consistent, therefore, with the concept that the factor causing the leukaemias was an oncogenic virus activated by X-irradiation.

Azathioprine-induced lymphocytic neoplasms of NZB mice lack ecotropic murine leukaemia virus.

NZB mice injected intramuscularly throughout a 6-month period with the immunosuppressant azathioprine (Imuran) developed lymphocytic lymphomas 6--7 months after treatment was initiated. These malignancies were quite distinct from the reticulum-cell neoplasia which occurs spontaneously in the strain, and were readily transplantable to NZB or histocompatible BALB/c recipients. Xenotropic, but not ecotropic murine leukaemia virus (MuLV) was detected in leukaemic tissues of some donor and recipient NZBs when tested in vitro by co-cultivation with permissive cell lines, genome rescue, XC and viral polymerase assays. Virus filtrates prepared from donor leukaemic tissues were non-pathogenic when injected into newborn C3H mice. These results are evidence against a mandatory ecotropic MuLV genome in lymphocytic neoplasia.

Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in F1 (BALB/c X NZB) hybrid mice derived by ovum transplantation.

F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information.

Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice.

When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results.