Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells.

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.     

Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent of EBV status.

BACKGROUND: In vitro the Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP-1) has been shown to upregulate expression of matrix metalloproteinase 9 (MMP-9), a member of a family of zinc dependent endopeptidases that is believed to facilitate tumour invasion and metastasis by degradation of the extracellular matrix. AIM: To test whether the expression of MMP-9 in Hodgkin's disease correlates with EBV status and survival and to investigate whether LMP-1 expression affects MMP-9 concentrations in the Hodgkin's disease cell line, L428. METHODS: MMP-9 expression was measured by means of immunohistochemistry in a series of Hodgkin's disease tumours and this expression was correlated with EBV status and survival. The influence of LMP-1 on MMP-9 expression was also investigated in the Hodgkin's disease cell line, L428. RESULTS: MMP-9 expression was demonstrated in the malignant Hodgkin and Reed-Sternberg cells of all (n = 86) formalin fixed, paraffin wax embedded Hodgkin's disease tumours examined. Although the intensity of MMP-9 immunostaining varied between cases, there was no correlation between MMP-9 expression and EBV status or survival. MMP-9 expression was also detected in a variety of non-malignant cells, including fibroblasts. MMP-9 was detected by zymography in the L428 and KMH2 Hodgkin's disease cell lines, whereas low or undetectable amounts of MMP-9 were found in the L591 Hodgkin's disease cell line. Induction of LMP-1 expression in the Hodgkin's disease cell line L428 did not result in a detectable increase in the values of MMP-9 as measured by zymography. CONCLUSIONS: These results demonstrate that MMP-9 is consistently expressed by the Hodgkin and Reed-Sternberg cells of Hodgkin's disease tumours and by the Hodgkin's disease cell lines, L428 and KMH2. However, this expression does not appear to be related either to LMP-1 values or to survival.     

Potential impact of conjugate vaccine on the incidence of invasive pneumococcal disease among children in Scotland

We sought to determine the potential impact of seven-valent pneumococcal conjugate vaccine on the incidence of invasive pneumococcal disease (IPD) among children in Scotland. Invasive pneumococci from blood and cerebrospinal fluid, isolated between 2000 and 2004 from all children aged less than 5 years in Scotland, were characterized by serotyping. Using reported efficacy data of the seven-valent pneumococcal conjugate vaccine (PCV7) along with likely coverage rates, we made an estimation of the potential impact on the incidence of IPD among children in Scotland. A total of 217 pneumococci were characterized into 22 different serogroups/types, the most common, in rank order, being 14, 19F, 6B, 18C, 23F, 9V, 4, 1, 19A, and 6A. Estimated serotype coverage for PCV7 was 76.5% in those aged less than 5 years of age but increased to 88.9% for those aged 1 year. By using serotype coverage and estimates of vaccine efficacy and uptake, the potential impact of the vaccine for those greater than 2 months of age, but less than 5 years, was estimated as 67.3%, leading to an average of 29 preventable cases per year. The introduction of PCV7 into the childhood immunization schedule would reduce the burden of pneumococcal disease in children, and the incidence would be particularly reduced in those children aged 1 year. Additional benefits may be gained in adults through herd protection. Continued surveillance of IPD is required before, during, and after the introduction of PCV7.     

The epidemiology of Newcastle disease in rural poultry: A review

Rural poultry are the dominant form of poultry kept in the developing world. They are a natural resource whose potential is not fully exploited for the welfare of rural populations. The most devastating disease of rural poultry is Newcastle disease (ND). ND is an epidemic disease in intensive poultry and is responsible for high economic losses. Its epidemiology in intensive poultry is well understood, but little has been published on its behaviour in village poultry populations. Some research has been carried out during the past few years and it now appears that rural poultry are receiving increasing support for research and development from many government and international funding agencies throughout the world. All strains of Newcastle disease virus (NDV) occur in rural poultry, but velogenic strains are reported to be more common. Serological surveys in conjunction with isolation studies have shown that velogenic NDV strains are endemic in rural poultry populations even in isolated villages and possibly in isolated flocks. Although NDV is endemic in village poultry, the clinical disease usually follows an epidemic pattern. ND outbreaks often occur once or twice a year at regular intervals affirming the endemicity of the virus, however, 'mini' outbreaks in individual flocks and sporadic cases in individual birds may occur. Epidemics usually occur at times of climatic stress, leading to seasonal occurrence. The spread of NDV within and between village poultry populations is relatively slow due to a low contact rate. The major mode of transmission appears to be by the faecal-oral route. The respiratory route may also play a role in flocks where close bird-to-bird associations exist. Other poultry species, wild and feral birds, wild animals, communal water reservoirs and domestic animals may play a role in transmission; however, their role has not been properly investigated. In non-immune, intensively reared poultry, introduction of a sufficient quantity of virulent NDV is sufficient to cause severe outbreaks, but in rural poultry epidemic disease depends upon a number of factors. These include NDV pathotype, age structure and immunity of the host population, breed susceptibility, concurrent disease and seasonal influences. Although ND is endemic in rural poultry, many aspects of the epidemiology and economics of ND have not been fully understood. Well-designed, longitudinal studies made within a socio-economic framework are required to improve our understanding of the main problems of rural poultry systems.     

Hodgkin's disease: an immunohistochemical and histological study

The distribution of immunoglobulin (Ig) in Hodgkin's tissue has been demonstrated in paraffin and cryostat sections by the unlabelled antibody peroxidase-antiperoxidase (PAP) method and the two-stage fluorescein isothiocyanate (FITC)-based technique. The morphology and histogenesis of the Reed-Sternberg (RS) and Hodgkin (HD) cells has been studied with the metalophil method of Marshall (1948) and this revealed a population of dendritic histiocytes which corresponded in number, sizes and distribution to the RS and HD cells in adjacent sections stained by haematoxylin and eosin. The largest RS cells, however, appeared to be non-dendritic. A notable feature of Hodgkin's tissue was the tendency for the dendritic cells to form "nodules", in combination with a population of small lymphocytes. The PAP technique reveals Ig in the form of mu and delta heavy chains, as well as kappa and lambda light chains, in close association with and probably on the surface of a high proportion of these lymphocytes, suggesting that they are immature B cells. Similar reactions were given by the mantle of lymphocytes of surviving normal lymphoid follicles, and metalophil dendritic histiocytes were also demonstrated within the mantle and subjacent part of the germinal centre. Numerous immunocytes containing Ig were present in all lesions; in the majority of cases, more cells contained gamma than alpha or mu heavy chains, although in these cases alpha-positive cells outnumbered those containing gamma or mu heavy chains. In two-thirds of the cases, one-third of the RS cells contained cytoplasmic immunoglobulin. This was exclusively gamma heavy, although both light chains were present. In about half the cases a minority of the HD cells contained gamma chain. The results suggest that HD and RS cells are dendritic histiocytes of the type normally found in the lymphoid follicles and that their tendency to form nodules in assoication with B lymphocytes is a manifestatin of this origin. It is suggested that the presence of Ig most probably results from absorption of antigen-antibody complexes on the cell surface.     

Colorectal juvenile polyps: an epidemiological and histopathological study of 144 cases in Jordanians

The minimal incidence rate of colorectal juvenile polyps in Jordanians was 1.4 per 100 000 in the general population and 2.8 per 100 000 in children under 10 years of age. Out of 144 cases, nine had two to seven polyps and one juvenile polyposis coli. There was male preponderance and a mean age of 8 years: 96.5% of the polyps were in the rectum. Characteristically, stromal oedema, inflammation, ulceration with granulation tissue cap formation and gland regeneration were present. Epithelial hyperplasia was not uncommon and focal dysplastic change was occasionally noted, being always accompanied by hyperplastic change. Focal severe dysplasia was seen in one solitary juvenile polyp. It is concluded that varying degrees of focal epithelial atypia can occasionally develop in solitary juvenile polyps, rarely reaching severe dysplastic change. Malignant transformation in the commonly seen form of juvenile polyp (solitary type) is probably a rare phenomenon, but its frequency needs further evaluation.     

The long view: a selective review of 40 years of Newcastle disease research

This review is written for the series celebrating the 40th year since the first issue of Avian Pathology. The aim of the authors was to cover the developments in Newcastle disease (ND) research over the last 40 years that they considered significant. During those 40 years there have been several panzootics of this serious disease in poultry and for the last 30 years there has been a continuing panzootic in domestic pigeons, which has spread to wild birds and poultry. The 40-year period began with worldwide outbreaks of severe ND, which served as an important impetus for ND research work. Although early work was concerned with controlling the disease, specifically by improving and developing new vaccines and vaccine regimens, even prior to the 1970s ND virus was seen as a useful laboratory virus for replication and virulence studies. This review covers the historical developments in the following areas: understanding the molecular basis of virulence; epidemiology and relatedness of different ND strains, both antigenically and genetically; the emergence of virulent strains and their relationship with viruses of low virulence; sequencing and understanding the viral genome and genes; the development of rapid molecular-based diagnostic tests; and the phylogeny and molecular taxonomy of ND virus. The authors suggest areas in which future research could or should be undertaken.     

The status of Newcastle disease and the use of V4 vaccine in Malawi

Data on the incidence of Newcastle disease in Malawi obtained from various sources including serological surveys, questionnaires and interviews, as well as statistics on laboratory-confirmed cases, showed the disease to be widespread throughout the country. Chickens vaccinated with La Sota and Komarov vaccine strains were often inadequately protected against the disease, especially those under smallholder management. Trials involving laboratory chickens and chickens under both intensive and smallholder management showed that V4 vaccine, given by eye-drop, drinking water and oral droplet methods, induced an antibody response sufficient to protect birds against challenge with virulent field isolates of Newcastle disease virus. V4 is recommended as an alternative to La Sota and Komarov vaccines, particularly for smallholder flocks, because of its thermostability, its ease of administration and its transmissibility. Large scale use of V4 appears to have reduced the incidence of Newcastle disease in rural parts of Malawi.     

Increasing incidence of melanoma in central Greece: a retrospective epidemiological study

The increasing incidence of melanoma in the general population during the last few decades has provoked a great deal of research, aiming to identify the possible relationship between old and new etiological factors involved in the pathogenesis of this tumor. The aim of the study was to evaluate the incidence of melanoma in central Greece, especially in the prefecture of Larissa from January 1988 to December 1998. Data were collected from the General Hospital of Larissa. Seventy-one cases of melanoma were studied (41 females, 30 males). The incidence increased from 1.36/100,000 patients during the first year of the study (1988) to 5.2/100,000 patients in the last year of the study (1998). The patients'skin types were: type 12.8%, type II 52.1%, type III 45.1%. The median age of patients was 61.9 years, 61.4 years in female and 62.5 years in male patients. Concerning their occupation, farmers accounted for 56.3%. Melanomas were most frequently located on head and neck (36.6%), extremities (30.98%) and trunk (11.3%). Superficial spreading melanomas were observed in 44% of the patients and nodular melanomas in 20%. In conclusion. there was a rapid increase in the incidence of melanoma in our region especially during the last 3 years.     

The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature

There has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease ‘protected’ from developing allergic (immunoglobulin E‐mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune‐based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co‐prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases.