Hydro-chemical responses at different scales in a rural catchment, UK, and implications for managing the unintended consequences of agriculture.

Diffuse pollutant transfers from agricultural land often constitute the bulk of annual loads in catchments and storm events dominate these fluxes. There remains a lack of understanding of how pollutants move through catchments at different scales. This is critical if the mismatch between the scales used to implement on-farm management strategies, compared to those used for assessment of environmental quality, is to be addressed. The aim of this study was to understand how the mechanisms of pollutant export may change when assessed at different scales and the corresponding implications for on-farm management strategies. A study was conducted within a 41 km2 catchment containing 3 nested sub-catchments, instrumented to monitor discharge and various water quality parameters. Storm data over a 24-month period were analysed and hysteresis (HI) and flushing (FI) indices calculated for two water quality variables that are typically of environmental significance; NO3-N and suspended sediment (SSC). For SSC, increasing spatial scale had little effect on the mechanistic interpretation of mobilisation and the associated on-farm management strategies. At the three smallest scales NO3-N was chemodynamic with the interpretation of dominant mechanisms changing seasonally. At these scales, the same on-farm management strategies would be recommended. However, at the largest scale, NO3-N appeared unaffected by season and chemostatic. This would lead to a potentially very different interpretation and subsequent on-farm measures. The results presented here underscore the benefits of nested monitoring for extracting mechanistic understanding of agricultural impacts on water quality. The application of HI and FI indicates that monitoring at smaller scales is crucial. At large scales, the complexity of the catchment hydrochemical response means that mechanisms become obscured. Smaller catchments more likely represent critical areas within larger catchments where mechanistic understanding can be extracted from water quality monitoring and used to underpin the selection of on-farm mitigation measures.

Detection of SARS-CoV-2 IgG antibodies and inflammatory cytokines in saliva-a pilot study.

Objective: The pandemic caused by SARS-CoV-2 virus continues to have a profound effect worldwide. However, COVID-19 induced oral facial manifestations have not been fully described. We conducted a prospective study to demonstrate feasibility of anti-SARS-CoV-2 IgG and inflammatory cytokine detection in saliva. Our primary objective was to determine whether COVID-19 PCR positive patients with xerostomia or loss of taste had altered serum or saliva cytokine levels compared to COVID-19 PCR positive patients without those oral symptoms. Our secondary objective was to determine the correlation between serum and saliva COVID-19 antibody levels. Materials and methods: For cytokine analysis, saliva and serum were obtained from 17 participants with PCR-confirmed COVID-19 infection at three sequential time points, yielding 48 saliva samples and 19 paired saliva-serum samples from 14 of the 17 patients. For COVID-19 antibody analyses, an additional 27 paired saliva-serum samples from 22 patients were purchased. Results: The saliva antibody assay had 88.64% sensitivity [95% Confidence Interval (CI) 75.44%, 96.21%] to detect SARS-CoV-2 IgG antibodies compared to serum antibody. Among the inflammatory cytokines assessed - IL-6, TNF-α, IFN-γ, IL-10, IL-12p70, IL-1ß, IL-8, IL-13, IL-2, IL-5, IL-7 and IL-17A, xerostomia correlated with lower levels of saliva IL-2 and TNF-α, and elevated levels of serum IL-12p70 and IL-10 (p < 0.05). Loss of taste was observed in patients with elevated serum IL-8 (p < 0.05). Conclusions: Further studies are needed to construct a robust saliva-based COVID-19 assay to assess antibody and inflammatory cytokine response, which has potential utility as a non-invasive monitoring modality during COVID-19 convalescence.

Diffuse water pollution during recent extreme wet-weather in the UK: Environmental damage costs and insight into the future?

Periods of extreme wet-weather elevate agricultural diffuse water pollutant loads and climate projections for the UK suggest wetter winters. Within this context, we monitored nitrate and suspended sediment loss using a field and landscape scale platform in SW England during the recent extreme wet-weather of 2019-2020. We compared the recent extreme wet-weather period to both the climatic baseline (1981-2010) and projected near- (2041-2060) and far- (2071-2090) future climates, using the 95th percentiles of conventional rainfall indices generated for climate scenarios downscaled by the LARS-WG weather generator from the 19 global climate models in the CMIP5 ensemble for the RCP8.5 emission scenario. Finally, we explored relationships between pollutant loss and the rainfall indices. Grassland field-scale monthly average nitrate losses increased from 0.39-1.07 kg ha-1 (2016-2019) to 0.70-1.35 kg ha-1 (2019-2020), whereas losses from grassland ploughed up for cereals, increased from 0.63-0.83 kg ha-1 to 2.34-4.09 kg ha-1. Nitrate losses at landscape scale increased during the 2019-2020 extreme wet-weather period to 2.04-4.54 kg ha-1. Field-scale grassland monthly average sediment losses increased from 92-116 kg ha-1 (2016-2019) to 281-333 kg ha-1 (2019-2020), whereas corresponding losses from grassland converted to cereal production increased from 63-80 kg ha-1 to 2124-2146 kg ha-1. Landscape scale monthly sediment losses increased from 8-37 kg ha-1 in 2018 to between 15 and 173 kg ha-1 during the 2019-2020 wet-weather period. 2019-2020 was most representative of the forecast 95th percentiles of >1 mm rainfall for near- and far-future climates and this rainfall index was related to monitored sediment, but not nitrate, loss. The elevated suspended sediment loads generated by the extreme wet-weather of 2019-2020 therefore potentially provide some insight into the responses to the projected >1 mm rainfall extremes under future climates at the study location.

Current advisory interventions for grazing ruminant farming cannot close exceedance of modern background sediment loss - Assessment using an instrumented farm platform and modelled scaling out.

Water quality impairment by elevated sediment loss is a pervasive problem for global water resources. Sediment management targets identify exceedance or the sediment loss 'gap' requiring mitigation. In the UK, palaeo-limnological reconstruction of sediment loss during the 100-150 years pre-dating the post-World War II intensification of agriculture, has identified management targets (0.20-0.35 t ha-1 yr-1) representing 'modern background sediment delivery to rivers'. To assess exceedance on land for grazing ruminant farming, an integrated approach combined new mechanistic evidence from a heavily-instrumented experimental farm platform and a scaling out framework of modelled commercial grazing ruminant farms in similar environmental settings. Monitoring (2012-2016) on the instrumented farm platform returned sediment loss ranges of 0.11-0.14 t ha-1 yr-1 and 0.21-0.25 t ha-1 yr-1 on permanent pasture, compared with between 0.19-0.23 t ha-1 yr-1 and 0.43-0.50 t ha-1 yr-1and 0.10-0.13 t ha-1 yr-1and 0.25-0.30 t ha-1 yr-1 on pasture with scheduled plough and reseeds. Excess sediment loss existed on all three farm platform treatments but was more extensive on the two treatments with scheduled plough and reseeds. Excessive sediment loss from land used by grazing ruminant farming more strategically across England, was estimated to be up to >0.2 t ha-1 yr-1. Modelled scenarios of alternative farming futures, based on either increased uptake of interventions typically recommended by visual farm audits, or interventions selected using new mechanistic understanding for sediment loss from the instrumented farm platform, returned minimum sediment loss reductions. On the farm platform these were 2.1 % (up to 0.007 t ha-1 yr-1) and 5.1 % (up to 0.018 t ha-1 yr-1). More strategically, these were up to 2.8 % (0.014 t ha-1 yr-1) and 4.1 % (0.023 t ha-1 yr-1). Conventional on-farm measures will therefore not fully mitigate the sediment loss gap, meaning that more severe land cover change is required.

An open and closed case: timing of closure following laparostomy.

INTRODUCTION: Laparostomy is important in the management of patients with intra-abdominal gastrointestinal catastrophe or trauma. It carries significant risk and is resource intensive, both in terms of nursing and surgically. The main goal is to achieve prompt myofascial closure (MFC) in order to minimise morbidity and mortality. Early MFC was initially defined as within 2-3 weeks but there is growing evidence that this should be measured in days. METHODS: Retrospective analysis was undertaken of laparostomy cases between 2016 and 2018 at an acute trust and trauma centre serving a population of 500,000. Indication, duration of open abdomen (OA), number of relook procedures and consultant presence were examined to see whether they affected MFC rates, morbidity and mortality. RESULTS: Overall, 76 laparostomies were performed during the 3-year study period. The most common indication was peritonitis (68.4%). As duration of OA and number of relook procedures increased, the chances of MFC fell significantly. After day 1, MFC rates fell by 20% with each subsequent 24 hours. Leaving the abdomen open primarily at index procedure compared with performing laparostomy following a postoperative complication was associated with significantly higher MFC rates (92.6% vs 68.2%, (p=0.006). The mortality rate was 15.8%. CONCLUSIONS: If the OA is not closed within five days or by the third relook procedure, then achieving MFC is unlikely. Alternative methods should be employed to close the abdomen rather than continuing to take the patient back to theatre for relook laparotomies while increasing the risk of morbidity and mortality. A proactive strategy to forming primary laparostomy at the index procedure has high closure rates.

Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial.

BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/µl. Regardless of alloimmunization status, CCIs < 5000/µl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

Rituximab for treatment of inhibitors in haemophilia A. A Phase II study.

The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates for it. The Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (RICH) study was a phase II trial to assess whether rituximab can reduce anamnestic FVIII antibody (inhibitor) titres. Male subjects with severe congenital haemophilia A and an inhibitor titre ≥5 Bethesda Units/ml (BU) following a FVIII challenge infusion received rituximab 375 mg/m² weekly for weeks 1 through 4. Post-rituximab inhibitor titres were measured monthly from week 6 through week 22 to assess treatment response. Of 16 subjects who received at least one dose of rituximab, three (18.8%) met the criteria for a major response, defined as a fall in inhibitor titre to <5 BU, persisting after FVIII re-challenge. One subject had a minor response, defined as a fall in inhibitor titre to <5 BU, increasing to 5-10 BU after FVIII re-challenge, but <50% of the original peak inhibitor titre. Rituximab is useful in lowering inhibitor levels in patients, but its effect as a solo treatment strategy is modest. Future studies are indicated to determine the role of rituximab as an adjunctive therapy in immune tolerisation strategies.

A novel application of natural fluorescence to understand the sources and transport pathways of pollutants from livestock farming in small headwater catchments.

This paper demonstrates the application of a low-cost and rapid natural fluorescence technique for tracing and quantifying the transport of pollutants from livestock farming through a small headwater catchment. Fluorescence intensities of Dissolved Organic Matter (DOM) present in different pollutant sources and drainage waters in the Den Brook catchment (Devon, UK) were monitored through storm events occurring between January 2007 and June 2008. Contrasting fluorescence signals from different sources confirmed the technique's usefulness as a tracer of pollutants from livestock farming. Changes in fluorescence intensities of drainage waters throughout storm events were used to assess the dynamics of key pollutant sources. The farmyard area of the catchment studied was shown to contribute polluted runoff at the onset of storm events in response to only small amounts of rain, when flows in the Den Brook first-order channel were low. The application of slurry to a field within the catchment did not elevate the fluorescence of drainage waters during storm events suggesting that when slurry is applied to undrained fields the fluorescent DOM may become quickly adsorbed onto soil particles and/or immobilised through bacterial breakdown. Fluorescence intensities of drainage waters were successfully combined with discharge data in a two component mixing model to estimate pollutant fluxes from key sources during the January 2007 storm event. The farmyard was shown to be the dominant source of tryptophan-like material, contributing 61-81% of the total event flux at the catchment outlet. High spatial and temporal resolution measurements of fluorescence, possibly using novel in-situ fluorimeters, may thus have great potential in quickly identifying and quantifying the presence, dynamics and sources of pollutants from livestock farming in catchments.

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age.

BACKGROUND: Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. OBJECTIVE: To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. METHODS: Facial photographs were collected of 250 Chinese women, aged 25-70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. RESULTS: Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans-epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. CONCLUSIONS: We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.

Rethinking the contribution of drained and undrained grasslands to sediment-related water quality problems.

Grass vegetation has been recommended for use in the prevention and control of soil erosion because of its dense sward characteristics and stabilizing effect on the soil. A general assumption is that grassland environments suffer from minimal soil erosion and therefore present little threat to the water quality of surface waters in terms of sediment and sorbed contaminant pollution. Our data question this assumption, reporting results from one hydrological year of observations on a field-experiment monitoring overland flow, drain flow, fluxes of suspended solids, total phosphorus (TP), and molybdate-reactive phosphorus (<0.45 mum) in response to natural rainfall events. During individual rainfall events, 1-ha grassland lysimeters yield up to 15 kg of suspended solids, with concentrations in runoff waters of up to 400 mg L(-1). These concentrations exceed the water quality standards recommended by the European Freshwater Fisheries Directive (25 mg L(-1)) and the USEPA (80 mg L(-1)) and are beyond those reported to have caused chronic effects on freshwater aquatic organisms. Furthermore, TP concentrations in runoff waters from these field lysimeters exceeded 800 mug L(-1). These concentrations are in excess of those reported to cause eutrophication problems in rivers and lakes and contravene the ecoregional nutrient criteria in all of the USA ecoregions. This paper also examines how subsurface drainage, a common agricultural practice in intensively managed grasslands, influences the hydrology and export of sediment and nutrients from grasslands. This dataset suggests that we need to rethink the conceptual understanding of grasslands as non-erosive landscapes. Failure to acknowledge this will result in the noncompliance of surface waters to water quality standards.

Reversal of the net dinitrogen gas flux in coastal marine sediments.

The flux of nitrogen from land and atmosphere to estuaries and the coastal ocean has increased substantially in recent decades. The observed increase in nitrogen loading is caused by population growth, urbanization, expanding water and sewer infrastructure, fossil fuel combustion and synthetic fertilizer consumption. Most of the nitrogen is removed by denitrification in the sediments of estuaries and the continental shelf, leading to a reduction in both cultural eutrophication and nitrogen pollution of the open ocean. Nitrogen fixation, however, is thought to be a negligible process in sub-tidal heterotrophic marine systems. Here we report sediment core data from Narragansett Bay, USA, which demonstrate that heterotrophic marine sediments can switch from being a net sink to being a net source of nitrogen. Mesocosm and core incubation experiments, together with a historic data set of mean annual chlorophyll production, support the idea that a climate-induced decrease in primary production has led to a decrease in organic matter deposition to the benthos and the observed reversal of the net sediment nitrogen flux. Our results suggest that some estuaries may no longer remove nitrogen from the water column. Instead, nitrogen could be exported to the continental shelf and the open ocean and could shift the effect of anthropogenic nitrogen loading beyond the immediate coastal zone.

Lessons learned from laparoscopic treatment of gastric and gastroesophageal junction stromal cell tumors.

BACKGROUND: Stromal cell tumors of the gastric and gastroesophageal junction are rare neoplasms that traditionally have been resected for negative margins using an open approach. This study aimed to evaluate the efficacy laparoscopic resection of gastric and gastroesophageal stromal cell tumors and the lessons learned from experience with this method. METHODS: This retrospective review evaluated all patients who underwent laparoscopic resection of gastric or esophageal stromal cell tumors at a tertiary referral center between December 2002 and March 2005. Medical records were reviewed with regard to patient demographics, preoperative evaluation, operative approach, tumor location and pathology, length of operation, complications, and length of hospital stay. RESULTS: A total of 12 consecutive patients with a mean age of 55 +/- 5.9 years were treated. Preoperative endoscopic ultrasound (EUS) was performed for 11 of 12 patients with a diagnostic accuracy of 100%, whereas EUS-guided fine-needle aspiration was performed for 10 of 12 patients with a diagnostic accuracy of 50%. Four patients with symptomatic gastroesophageal junction leiomyomas were treated with enucleation and Nissen fundoplication. Eight patients were treated with laparoscopic wedge resection of gastric lesions. Complete R0 resection was achieved for all the patients undergoing laparoscopic resection. Intraoperative endoscopy was performed for four patients and resulted in shorter operative times. The average operative time for this entire series was 169 +/- 17 min: 199 +/- 24 min for the first six cases and 138 +/- 19 min for the last six cases. The median hospital length of stay was 2 days. One patient with esophageal leiomyoma had persistent dysphagia at the 12-month follow-up assessment. There were no other complications and no deaths in this series of patients. CONCLUSIONS: Laparoscopic resection of gastric and gastroesophageal junction stromal cell tumors may be performed safely with low patient morbidity. This approach can achieve adequate surgical margins and lead to short hospital stays. Improvements in the technique have led to shorter operative times.

[Ischaemia of the lower limbs: anaesthesia and intensive care]. / Anesthésie-réanimation d'un patient en ischémie aiguë des membres inférieurs.

OBJECTIVES: To appreciate the severity of a patient with acute limb ischaemia, to know how to manage these patients during the perioperative period. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: acute limb, ischaemia, prognosis, complications, rhabdomyolysis, hyperkalaemia, compartment syndrome, fasciotomy. DATA SYNTHESIS: Ischaemia of the lower limbs is a medico-surgical emergency. The ischaemia implies a decrease of cellular energetic stocks and an increase in intracellular calcium. During reperfusion, the calcium paradox is exacerbated and ROS formation produces membrane damage. Tissue oedema and a local and general inflammatory syndrome occur. Clinical symptoms of acute ischaemia include pallor, pulselessness, decrease of temperature and pain. Occurrence of neurological symptoms is a sign of severity. Prognosis of patients relates directly to preexisting collateral circulation, aetiology of the occlusion (thrombosis vs embolus), duration of ischaemia, topography of the occlusion (severity of proximal occlusions as the acute aortic occlusion), and co-morbidity (renal failure, heart failure). The temperature of the ischaemic limb, quality of the downstream circulation, extension of the thrombus, arterial pressure and association to a venous thrombosis are other prognostic factors of lower limb ischaemia. The first treatment to be initiated is high doses of heparin. Once the diagnosis is made, the number of preoperative tests will be as small as possible because of the urgency of revascularization. Arteriography will be performed only when really needed and when its realization will not delay revascularization and will not alter the patient's prognosis. Where general anesthesia is required, the choice of anaesthetic agents will be based on their haemodynamic stability. During severe acute limb ischaemia, monitoring of invasive pressure is recommended, as well as regular dosages of potassium, arterial gases and CPK. Preoperatively in case of severe ischaemia, (proximal occlusion lasting more than 6 hours), preventive treatment, including controlled reperfusion with heparinized serum is indicated. Surveillance and prevention of a rhabdomyolysis and renal failure are imperative. Immediately after reperfusion, a dosage of potassium must be performed; moreover that hyperkalaemia is favoured by acidosis or renal failure. Postoperative haemodialysis is performed in case of hyperkalaemia or renal failure. Occurrence of compartment syndrome has to be checked and fasciotomy must be performed in case of a doubt on the microcirculation integrity.

Silent infarcts in children with sickle cell anemia and abnormal cerebral artery velocity.

BACKGROUND: A substantial minority of neurologically normal children with sickle cell disease have lesions consistent with cerebral infarction as seen on magnetic resonance imaging (MRI). OBJECTIVES: To determine if transfusion therapy affects the rate at which silent infarcts develop and to evaluate the contribution of MRI of the brain to stroke prediction by transcranial Doppler (TCD) ultrasonography. STUDY DESIGN: Children with elevated TCD ultrasonographic velocity were randomized to receive long-term transfusion therapy or standard care. Magnetic resonance imaging of the brain was obtained at randomization, annually, and with clinical neurologic events. The risk for new silent lesions and/or stroke was compared for each treatment arm. RESULTS: Among the 37% of subjects with silent infarcts, those receiving standard care were significantly more likely to develop new silent lesions or stroke than were those who received transfusion therapy. For subjects receiving standard care, those with lesions at baseline were significantly more likely to develop stroke or new silent lesions than those whose MRI studies showed no abnormality. CONCLUSIONS: Transfusion therapy lowers the risk for new silent infarct or stroke for children having both abnormal TCD ultrasonographic velocity and silent infarct. However, those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality. The finding of a silent infarct reinforces the need for TCD ultrasonographic screening and consideration of transfusion therapy if the abnormalities are seen. Similarly, elevated TCD ultrasonographic velocity warrants MRI of the brain because children with both abnormalities seem to be at increased risk for developing new silent infarct or stroke.

Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction.

LIGHT, a member of the TNF family of cytokines (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator, a receptor expressed on T cells), is induced on activated T cells and mediates costimulatory and antitumor activity in vitro. Relatively little information is available on the in vivo effects of LIGHT expression, particularly within the T cell compartment. In this work, we describe transgenic mice that express human LIGHT under the control of the CD2 promoter, resulting in constitutive transgene expression in cells of the T lymphocyte lineage. LIGHT-transgenic animals exhibit abnormalities in both lymphoid tissue architecture and the distribution of lymphocyte subsets. They also show signs of inflammation that are most severe in the intestine, along with tissue destruction of the reproductive organs. These LIGHT-mediated effects were recapitulated when immune-deficient mice were reconstituted with bone marrow from LIGHT-transgenic donor mice. T cells in the LIGHT-transgenic mice have an activated phenotype and mucosal T cells exhibit enhanced Th1 cytokine activity. The results indicate that LIGHT may function as an important regulator of T cell activation, and implicate LIGHT signaling pathways in inflammation focused on mucosal tissues.

Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis.

LIGHT is a member of the TNF cytokine superfamily that signals through the lymphotoxin (LT)beta receptor and the herpesvirus entry mediator. LIGHT may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus, which may provide significant selective pressure shaping the evolution of LIGHT. Here, we define the molecular genetics of the human LIGHT locus, revealing its close linkage to the TNF superfamily members CD27 ligand and 4-1BB ligand, and the third complement protein (C3), which positions LIGHT within the MHC paralog on chromosome 19p13.3. An alternately spliced isoform of LIGHT mRNA that encodes a transmembrane-deleted form is detected in activated T cells and gives rise to a nonglycosylated protein that resides in the cytosol. Furthermore, membrane LIGHT is shed from the cell surface of human 293 T cells. These studies reveal new mechanisms involved in regulating the physical forms and cellular compartmentalization of LIGHT that may contribute to the regulation and biological function of this cytokine.

The helper virus envelope glycoprotein affects the disease specificity of a recombinant murine leukemia virus carrying a v-myc oncogene.

Many retroviruses that carry oncogenes (acute transforming viruses) are generally replication-defective and therefore require co-infection with a replication competent 'helper' retrovirus for infectivity. The helper virus provides the retroviral proteins necessary for particle production and infection. These include the envelope glycoproteins that specifically bind to cell surface receptors and mediate viral adsorption and entry. Thus, a particular helper virus may influence the nature of disease induced by an oncogene-containing retrovirus due to tissue tropism of the helper. In a previous study, a replication-defective recombinant Moloney murine leukemia virus containing the v-myc oncogene was generated (M-MuLV(myc); Brightman B.K., Pattengale P.K., and Fan H., J Virol 60: 68-81, 1986). When M-MuLV(myc) was inoculated into mice using the non-pathogenic amphotropic murine leukemia virus (Am-MuLV 4070) as a helper, T- and B-lymphoblastic lymphomas resulted with the following two surface phenotypes, namely, (1) Thy 1.2+, B220- and (2) Thy 1.2-, B220+. Thy 1.2 surface antigen is characteristic of cells of the lymphoid lineage, whereas B220 surface antigen is characteristic of cells of the B-lymphoid lineage. In these experiments, to assess the influence of the helper virus on the disease specificity of M-MuLV(myc), two weakly pathogenic ecotropic helper MuLVs that interact with different cell surface receptors than Am-MuLV (Mo+PyF101 and AKV MuLV) were used to pseudotype M-MuLV(myc). In both cases, when inoculated into mice, these pseudotypes induced only T-lymphoblastic lymphoma. These results indicate that for M-MuLV(myc) the types of the tumors induced are influenced by the helper virus utilized, and they suggest that different lymphoid cells may express different levels of retroviral receptors.