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R F Jarrett

Publications and source records attributed to R F Jarrett.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin's disease.

Epstein-Barr virus (EBV) is associated with around one-third of cases, but young adult cases are rarely EBV associated. In this study, known oncogenic DNA viruses, including human adenoviruses, papovaviruses and the human herpesviruses-6 (HHV-6) and -8 (HHV-8) were not detected in Hodgkin's disease lesions. These results suggest that an as yet unidentified infectious agent is involved in the pathogenesis of non-EBV-associated Hodgkin's disease.

Adolescent↗
PubMed1998

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis.

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).

Adolescent↗
PubMed1997

Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.

There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.

Adolescent↗
PubMed1997

Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data.

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+ years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR = 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process.

Adolescent↗
PubMed1996

"Cytomegalovirus disease" in renal allograft recipients: is human herpesvirus 7 a co-factor for disease progression?

Fifty-six renal allograft recipients were studied prospectively for 3 months or longer after transplant. The polymerase chain reaction (PCR) was used to screen peripheral blood leucocyte (PBL) specimens for CMV, human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7) DNA (DNAemia) in 67 healthy controls and in serial (fortnightly) PBL specimens from the 56 allograft recipients. None of the healthy controls had detectable CMV DNAemia, although HHV6 and HHV7 DNAemia was found in 7% and 9% of individuals respectively. In contrast, DNAemia due to CMV, HHV6 and HHV7 was found in 50%, 36% and 39% of patients respectively, at some time during the post-transplant period. Of the 28 patients who had CMV DNAemia, eight developed "CMV disease". The risk of progression to "CMV disease" was increased in patients with concurrent DNAemia to all three viruses (relative risk 3.7; 95% CI 1.3-10.5). The relative risk of "CMV disease" for patients with concurrent CMV and HHV7 was also increased (RR = 3.5; 95% CI = 1.1-11.6), while the association between CMV and HHV6 was inconclusive (RR = v2.1; 95% CI = 0.7-6.6). The first 26 patients recruited to the study also had serial serum samples tested for antibody responses to the three viruses. "CMV disease" was associated with rising antibody titres to HHV7 (Fisher's exact test, P = 0.02), and weakly so with HHV6 (P = 0.07). It is concluded that in patients with CMV DNAemia, concurrent infection/reactivation HHV7 (and possibly HHV6) is associated with an increased risk of progression to "CMV disease".

Adolescent↗
PubMed1996

The epidemiology of Hodgkin's disease.

Much of the epidemiological heterogeneity of HD incidence reflects the behaviour of the NS subtype, at least in the USA. Incidence variation across races (except Asians) and time periods is most marked in this subtype. In young adults with HD, there is compelling evidence for social class modification of risk consistent with an infectious aetiology; limited data suggest that this effect occurs within the NS subtype, but considerable evidence indicates that it does not primarily involve EBV infection. Findings from familial aggregation studies and HLA associations point to inherited susceptibility to this subtype. Despite little sex difference for NS in young adulthood in the latest incidence data, parity nevertheless appears to be protective against this subtype for women. Therefore, the greater increase for females than males in the incidence of young-adult NS in recent years may reflect the impact of population trends towards later childbearing and lower parity. This change, as well as the concomitant smaller family sizes and growing affluence, could explain part of the burgeoning incidence of NS in young adults in the USA. These observations suggest that NS in young adults constitutes a separate disease, probably of infectious origin. The incongruous occurrence of this subtype in older adults, and the presence of EBV in some NS cases, could reflect heterogeneity within NS, for example, representing features of the cellular phase of NS (Cozen et al, 1992; Medeiros and Greiner, 1995). For the non-NS subtypes, many of the factors that predict risk of NS may also be relevant. Patterns of social class determinants in children and older adults, the age groups at risk for MC, support involvement of an infectious precursor given intense exposure, and EBV is a likely candidate, based on its high prevalence in these groups. However, little aetiological research has been directed explicitly at the non-NS subtypes. Considerable effort has gone into exploring an infectious aetiology of HD. Recently, this line of investigation has moved beyond social class determinants to molecular epidemiological studies of EBV and, to a lesser degree, other potentially involved viruses. The roles of genetic susceptibility and sex hormones also represent promising areas for exploration, particularly in their possible interaction with infectious agents and other environmental factors. Ultimately, clearer epidemiological understanding of HD will be aided by more precise classification of this disease at the molecular level.

Adult↗
PubMed1995

Case clustering, Epstein-Barr virus Reed-Sternberg cell status and herpes virus serology in Hodgkin's disease: results of a case-control study.

The Leukaemia Research Fund Data Collection Study (DCS) is a specialist registry of leukaemias and lymphomas. The present study involves 494 cases of Hodgkin's disease (HD) registered with the DCS between 1985 and 1989. This entire data set has been tested for localised spatial clustering using an established nearest neighbour method with 18% of all cases in young people classified as clustered (P < 0.05). No clustering was found in older cases. Subsamples were selected from the registered cases for a pilot study in which case clustering, herpes virus antibody titres and Epstein-Barr virus (EBV) presence within the Reed-Sternberg (RS) cells (EBV-RS status) were investigated together. Firstly, a case-control study of HD in young people or nodular sclerosing (NS) subtype (39 HD cases and 26 healthy controls) found significant elevation of antibody titres to EBV-viral capsid antigen (VCA), EBV-early antigen (EA) and human herpes virus 6 (HHV-6) in HD cases compared with controls. EBV viral genome was present in 5 cases and 4 of these were in clusters of HD in young people. Elevation of antibody titres to the EBV antigens was not associated with case clustering or EBV-RS status. Antibody titres to HHV-6 differed significantly between EBV-RS+ and EBV-RS- cases (P = 0.04). Geometric mean titres for HHV-6 for EBV-RS+ and EBV-RS- cases were 11.5 and 73.7, respectively, with the former lower than the control value of 20.5. Secondly, a cluster study included all other cases (n = 14) in clusters containing known EBV-RS+ cases. 3 further cases were EBV-RS+ positive but no cluster consisted entirely of positive cases. Overall, 5/16 clustered, 2/12 peripheral and 1/25 random cases in these studies were EBV-RS+ (P = 0.017). The interpretation of these results in terms of shared aetiological exposures of cases within clusters and the roles of EBV and HHV-6 is discussed, and hypotheses for testing in future studies proposed.

Adolescent↗
PubMed1994

A model to study viral and cytokine involvement in Sjögren's syndrome.

To investigate mechanisms that may be important in the pathogenesis of Sjögren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La are common in SS and it has been proposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advenovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-gamma resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as an in vitro model to study mechanisms of autoimmunity in SS.

Autoantigens↗
PubMed1993

Viruses and Hodgkin's disease.

Hodgkin's disease (HD) is a heterogeneous condition with distinct histological and epidemiological subgroups. Recent data provide evidence that the Epstein-Barr virus (EBV) is associated with a significant proportion of cases. Clonal EBV genomes have been detected in affected tissues and EBV has been localised to RS cells. The significance of these findings is reinforced by the detection of the EBV latent gene product LMP-1, which has known transforming potential, within RS cells in EBV-associated cases. The age distribution of EBV-associated cases is non-random. Paediatric cases, particularly those aged < 10 years, are likely to be EBV-associated as are older adult cases. In contrast, a smaller proportion of young adult cases is EBV-associated, and nodular sclerosis HD cases within this age group are positive infrequently. The results of our studies provide support for the hypothesis that HD has multiple aetiologies but do not support the polio model. The epidemiological evidence suggesting that HD may have an infectious aetiology is strongest for the young adult age group. EBV was suggested as a candidate virus however it is in these cases that there is least evidence for involvement of EBV. It would seem plausible that another virus, possibly another common childhood infectious agent, is responsible for the incidence peak seen in this age group in developed countries.

Age Factors↗
PubMed1992

Viral involvement in Hodgkin's disease.

The etiology of Hodgkin's disease (HD) is unknown, but a growing body of evidence suggests that the Epstein-Barr virus (EBV) plays a role in a proportion of cases. Clonal EBV genomes have been detected in affected tissues, and EBV has been localized to Reed-Sternberg (RS) cells, the putative malignant cells in HD. EBV latent genes, including the EBER RNAs and the latent membrane protein, LMP-1, are expressed by RS cells. These data suggest that EBV is playing a role in the pathogenesis of HD; however, it is clearly not involved in all cases. Using in situ hybridization, we can detect EBV within the RS cells in approximately 40% of cases. Epidemiological data suggest that HD is a heterogeneous condition and the distribution of EBV-associated cases is not random. Studies from several groups indicate that mixed cellularity cases are more likely to be EBV-associated than nodular sclerosis cases. Our data further suggest that the majority of pediatric and older cases of HD are EBV-associated, whereas the RS cells in young adult cases only rarely harbor EBV. We therefore speculate that another virus is responsible for the young adult peak in incidence which is seen in developed countries.

Adult↗
PubMed1992

Hodgkin's disease.

The epidemiological features of Hodgkin's disease (HD) suggest that it is a heterogeneous condition which may have different aetiologies in different age groups. The risk factors for the development of HD in young adults suggest that delayed exposure to a common infectious agent may be involved in this age group. Seroepidemiological studies have shown that HD patients have elevated antibody titres to Epstein-Barr virus (EBV) and the elevated titres have been shown to precede the diagnosis of HD. Recent molecular studies provide support for the idea that EBV is involved in the pathogenesis of HD. EBV genomes are consistently found in a proportion of tumour biopsies, the EBV-infected cells are clonal and the EBV genomes have been localized to Reed-Sternberg cells. Furthermore, EBV latent gene products are expressed by the Reed-Sternberg cells. The majority of HD samples from patients aged greater than 50 years and less than 15 years are EBV positive, whereas the minority (less than 15%) of samples from young adults contain detectable EBV DNA. The results suggest that EBV plays a role in HD in children and older adults but that other agents, possibly other viruses, are involved in young adults.

Adolescent↗
PubMed1992

Hodgkin's disease and Epstein-Barr virus.

Seroepidemiological and molecular biological studies have established an association of Hodgkin's disease with Epstein-Barr virus (EBV). Recently, EBV genomes and gene products, most notably the latent membrane protein (LMP), have been detected in approximately 50% of the cases. The findings suggest that EBV may contribute to the pathoetiology of a sizable proportion of Hodgkin's disease cases.

Antigens, CD↗
PubMed1992

The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease.

A series of 33 cases of Hodgkin's disease was investigated for the presence of the EBV encoded latent gene product LMP-1 and of CD23 using immunohistochemical techniques. The expression of bcl-2 was examined in a subset of cases. LMP-1 was detected in the Reed-Sternberg cells in 15 cases. Although LMP-1 is known to upregulate CD23 and bcl-2, there was no correlation between the expression of LMP-1 and the detection of CD23 and bcl-2 in Reed-Sternberg cells.

Adolescent↗