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Previous studies of nasopharyngeal carcinoma (NPC) have found elevated risks with higher consumption of salted fish and preserved foods, particularly during childhood. These foods can contain high levels of nitrosamines; however, most studies have not estimated exposure to nitrosamines directly. We conducted a case-control study in Taiwan to evaluate dietary intakes and NPC risk. A total of 375 cases (99% response rate) and 327 controls (88% response rate) were interviewed about their diet as an adult and at age 10 using a food-frequency questionnaire. We interviewed mothers of participants about their child's diet at age 10, age 3 and during weaning and the mother's diet while she was breast-feeding. Mothers of 96 cases and 120 controls were interviewed. Nitrosamine and nitrite levels were assigned to 66 foods based on published values. Intake of nitrosamines and nitrite as an adult was not associated with risk of NPC. High intakes of nitrosamines and nitrite during childhood and weaning were associated with increased risks of NPC for foods other than soy products. Adjusted odds ratios for the highest quartile were 2.2 [95% confidence interval (CI) 0.8-5.6] for age 10, 2.6 (95% CI 1.0-7.0) for age 3 and 3.9 (95% CI 1.4-10.4) for weaning diet. Intakes of nitrite and nitrosamines from soybean products during childhood and weaning were inversely associated with risk. Soybeans contain known inhibitors of nitrosation, and thus may explain the inverse association we observed. Our results suggest that nitrosamine and nitrite intake during childhood may play a role in the development of NPC.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

Epstein-Barr virus (EBV) has recently been identified in the tumor cells of patients with gastric carcinoma. We tested pre-morbid serum samples from a carefully monitored cohort of Japanese men in order to investigate the possibility that patients with EBV-associated gastric cancer represent a sub-set of individuals with long-standing difficulties in appropriately managing EBV infection. From a serum bank, we obtained 108 samples derived from 54 patients destined to develop gastric adenocarcinoma and 54 controls. Samples were tested under code for antibodies to EBV-capsid antigen, early antigen and nuclear antigen. Individuals who were positive for IgA antibodies against EBV viral-capsid antigen (VCA) and IgG antibodies against the R component of EBV early antigen were at a 3.9-fold and 1.9-fold excess risk of disease, respectively. Antibody titers to EBV VCA were significantly higher in those destined to get EBV-associated gastric cancer than those subsequently developing non-EBV-associated gastric cancer or age-and-gender-matched controls. These findings suggest that the inability to control EBV infection on a long-term basis exists many years prior to the development of EBV-associated gastric cancer, and that EBV may play an etiologic role in this sub-set of malignancies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

We assessed the relationship of Epstein-Barr virus (EBV) serology to the presence or absence of EBV genome in 39 cases of Hodgkin's disease (HD). Biopsies from patients included in 2 previous published studies, 1 involving patients from the United States (eastern Massachusetts) and 1 from Denmark, were evaluated for EBV (EBER-1) and latent membrane protein (LMP-1). The presence of EBV in Reed-Sternberg cells in the biopsies correlated with the histologic subtype of HD (mixed cellularity and lymphocyte depletion) but not with IgG antibody titers against the viral capsid antigen (VCA). These data suggest that, unlike Burkitt's lymphoma, the IgG antibody against VCA is not predictive of the presence or absence of EBV in Reed-Sternberg cells in HD. The predictive value of other antibodies should be evaluated.

Human T-cell lymphotropic virus Type I (HTLV-I) is the primary etiologic factor for adult T-cell leukemia/lymphoma (ATL). Although HTLV-I is endemic in Japan and the Caribbean islands, the reported clinical and epidemiologic features of ATL in these 2 parts of the world are quite different. ATL has been diagnosed at a younger age and is reported more frequently as the lymphomatous type rather than the acute type with leukemia in the Caribbean basin as compared with the presentation in Japan. In order to characterize ATL in the United States, a registry has been established at the National Cancer Institute for the purpose of recording all cases originally diagnosed in the United States. This registry was utilized to examine the effect of ethnic differences on age of onset and clinical features of ATL, using the same data base. Clinical and laboratory information was obtained from 177 patients suspected of having ATL, who were treated at the National Institutes of Health, or had biological samples sent for evaluation, or were reported in the literature. Histopathologic review and virologic studies were performed by standardized methods. Of 177 patients registered, 127 were considered as having ATL, according to an algorithm combining clinical, pathologic and laboratory features. Presenting features in the confirmed cases consisted primarily of lymphadenopathy (76.6%), hypercalcemia (72.5%), leukemia (82%), skin involvement (48.2%) and hepatomegaly (53.6%). Patients of Japanese ancestry were generally older (median age 63, range 51 to 73 years) than patients of African-American descent (median age 39, range 7 to 75 years) and presented more often with leukemia (90 vs. 69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Mapping the geographic distribution of human T-lymphotrophic virus types 1 and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type I) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types.

Experiments were designed in an attempt to identify T- and B-cell epitopes expressed on the 17-kDa early-antigen-restricted (EA-R) polypeptide of the EBV-induced early antigen complex. Using Berzofsky's algorithm, 3 hypothetical T-cell epitopes on p17 were synthesized and employed in EBV-specific lymphoproliferative assays. Lymphocytes from all EBV-infected donors responded against one of these epitopes (p17.1) irrespective of their serological status relative to antibodies to EA-R. Both CD4+ and CD8+ T-cell subpopulations from seropositive donors proliferated in the presence of p17.1 in short-term cultures. These experiments therefore identified one T-cell epitope on the 17-kDa polypeptide. In contrast, sera from anti-Ea antibody-positive individuals reacted with all 3 synthetic peptides to varying degrees, with p17.1 being the most frequently reactive epitope. When the sera were grouped according to diagnosis, it was noted that 82% of the sera from patients with aggressive lymphomas, whether Africans with Burkitt's lymphoma or North Americans with intermediate-grade large-cell or high-grade B-cell lymphoma, contained antibody reactive with p17.1, while 64% were reactive with p17.2 and 29% with p17.3. In contrast, high anti-EA antibody-positive sera from nasopharyngeal carcinoma patients were relatively less reactive with these synthetic peptides (23% positive with p17.1; 19% with p17.2; and 13% with p17.3). These results therefore identified 3 B-cell EA-R epitopes which might be potentially useful for clinical or epidemiological studies of EBV-associated lymphoproliferative diseases.

This report reviews the natural history of hemophilia and the development of concentrates as the preferred form of treatment and discusses the nature of immune defect in persons with hemophilia. It examines the risk of hepatitis and effect of HIV infection on treatment protocols, and it surveys the status of the safety of modern concentrates and what we have to look forward to in the future.

Serial serum samples from 37 patients with Hodgkin's disease (HD) and 39 healthy controls were studied for antibodies to human herpes virus-6 (HHV-6) using ELISA and indirect immunofluorescent antibody (IFA) tests and to the Epstein-Barr virus (EBV) using a radio-complement fixation assay. Antibodies to HHV-6 in the pre-treatment sera from the HD patients were not significantly different from those of controls, but significant changes in titers related to clinical course were noted among the HD patients. HHV-6 IFA titers increased significantly in the course of follow-up in patients who relapsed and decreased significantly over time in patients who did not. These serologic studies support tissue-based investigations indicating that EBV plays a greater etiologic role in HD than HHV-6, although HHV-6 serology may be of prognostic value or may assist in identifying individuals with immunologic abnormalities. The identification of diverse HHV-6 antibody patterns using different assays may reflect the presence of a number of antibodies with varying implications, similar to those identified for EBV.

Monoclonal antibodies (MAbs) were developed against immunodominant HHV-6 (GS isolate) late and early proteins. The major late protein was identified as a probable glycoprotein with a molecular weight of approximately 110 kDa (gp 110). Immunoblotting of the early antigen yielded proteins of 41 and 38 kDa (p41/38). The MAb to the early protein reacted with cells infected with 14 different HHV-6 isolates. In contrast, the MAb against the late protein reacted with only 10 of these isolates, indicating that there was strain variation in this glycoprotein. The percentage of antibody-positive sera reactive with gp110 in the ELISA ranged from 56% to 96% among the different serum donor categories. In contrast, only 10-30% of the sera were positive for antibodies to p41/38 with the exception of sera from patients with African Burkitt's lymphoma (ABL) and Hodgkin's disease (HD). These antibody patterns denote the presence of active HHV-6 replication in patients with ABL and HD.

Greenland Eskimos comprise an ethnic group with one of the highest recorded incidence rates for nasopharyngeal carcinoma in the world. Sera from 625 Eskimos and 73 Danes (Caucasians) living in Greenland, as well as from 62 Danes living in Denmark, were tested for complement-fixing antibody to Epstein-Barr virus (EBV) soluble antigen and, from this study group, 129 donors were matched by age and sex for a study comparing antibody to viral capsid antigen, early antigen, and soluble antigen. Both Eskimos and Danes living in Greenland had significantly higher titers of EBV antibodies than Danes living in Denmark, suggesting that environment was more important than genetics or socio-economic factors in determining the antibody response to EBV. Age and sex were also factors, higher titers occurring in females and young Eskimos.

Biopsies obtained from 74 Tunisian women with breast cancer (33 cases), benign breast disease (17 cases), and cervical cancer (24 cases) were assayed for the presence of an antigen cross-reacting with gp52 of the mouse mammary tumor virus (MMTV) in order to determine the frequency and possible prognostic significance of this antigen in a form of rapidly progressing breast cancer designated poussée évolutive or PEV. Antigen was detected in 23/33 breast carcinomas (70%) but in none of the 41 control specimens. An evaluation of reactivity according to tumor aggressiveness and survival could be performed in retrospect on 29 of the breast cancer patients with a follow-up of up to 11 years. The frequency of gp52-related antigen was similar in the patients with the most aggressive form of PEV with inflammatory signs (8/12 or 67% positive) and those breast cancer patients without PEV (12/17 or 71% positive). Within each of the two groups, PEV+ and PEV 0, no correlation was observed between the presence or absence of antigen and the disease-free interval or survival. We conclude that the identification of gp52-related antigens in the breast cancer biopsies from North African women has implications different from those observed in other populations. While thus far not indicative of disease aggressiveness and prognosis, the higher frequency of detectable antigen in comparison to biopsies obtained from patients born in the United States and Europe may have relevance to the etiology and pathogenesis of the disease.

In a comparative study of populations at high and low risk of nasopharyngeal carcinoma (NPC), sera from 442 Eskimo and 770 Danish children and adolescents were tested for the presence of antibodies against Epstein-Barr virus (EBV). Eskimo children in Greenland were seropositive at an early age and showed significantly higher titers of IgG antibody to the viral capsid antigen (VCA) (p less than 0.0001) and soluble (S) antigen (p less than 0.005) than Danes matched for age and sex, but had similar levels of IgA antibody to VCA and IgG antibody to the early antigen (EA). The high geometric mean VCA (IgG) titers found in certain age groups of Eskimo children were as high as those previously reported from areas in Africa highly endemic for Burkitt's lymphoma. In Greenland, neither location nor household size was a determining factor for prevalence or titer of VCA (IgG). The high antibody titers among Eskimo children probably reflect exposure to a large inoculum of EBV at the time of primary infection, infection early in life and/or re-exposure due to the higher incidence of EBV infection in Greenland. In view of the high incidence of NPC in Greenland and the known association of this tumor with EBV, we speculate that the time and quantitative aspects of the primary infection are also factors of relevance in the etiology of NPC.

A unique association of Epstein-Barr virus (EBV) with the undifferentiated nasopharyngeal carcinoma (NPC) is a well acknowledged phenomenon. We report here the detection of a factor present in the sera of NPC patients which inhibits the blastogenic response of lymphocytes from EBV seropositive individuals to EB virions or soluble antigens. This lymphocyte-stimulation inhibitor (LSI) was found to be associated with the IgA fraction of the serum immunoglobulins. No inhibitory activity was detected in the sera and their immunoglobulin fractions from healthy (both EBV-seropositive and seronegative) individuals and patients with other carcinomas of the head and neck region. Interestingly, the IgA-LSI was absent in the sera of NPC patients who were successfully treated and remained in remission, while it was readily detectable in the sera of NPC patients in relapse, LSI-positive IgA fractions did not inhibit mitogenic response of lymphocytes to phytohemagglutinin. Taken together, the data presented suggest that LSI is a specific inhibitor of the response of sensitized lymphocytes to EBV antigens and that it may indeed represent a marker of great clinical significance regarding undifferentiated nasopharyngeal carcinoma, particularly for its prognosis.

Four steroids and one protease inhibitor were evaluated for their effects on 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced and Epstein-Barr virus-induced early antigens (EBV-EA) in Raji cells. Continuous treatment with dexamethasone, prednisolone, hydrocortisone and cortisone inhibited TPA-induced EBV-EA to varying degrees, but the protease inhibitor N-alpha-p-tosyl L-lysine chloromethyl ketone-HCl (TLCK) had no significant effect. None of the agents tested inhibited EBV- induced EA. In addition, the effect of the steroids was reversible since the removal of these agents resulted in recovery of the percentage of EBV-EA-positive cells in TPA-treated cultures. These results were in agreement with the in vivo experiments of other investigators, who demonstrated inhibition of tumor promotion with steroids. Since TLCK failed to inhibit TPA-induced EA, it is unlikely that induction of EA by TPA is the result of production of proteases.

Delayed hypersensibility to antigens derived from four lymphoid cell lines was measured in 27 non-Chinese patients with nasopharyngeal cancer (NPC) and 63 non-NPC cancer patients. Of the NPC patients, 17/27 (63%) had a positive skin test response to antigens derived from HKLY-28, a lymphoid cell line which was developed from an NPC biopsy. Only 10/51 (20%) and 1/13 (8%) patients with solid tumors and hematopoietic malignancies, respectively, had positive skin test responses to HKLY-28. Positive skin tests were found less frequently when extracts from cell lines derived from normal individuals or lymphoma patients were utilized, although NPC patients were more reactive to two of the non-NPC derived cell lines than the controls. The NPC patients in this study also had significantly elevated antibody titers to the Epstein-Barr virus (EBV), capsid antigen (VCA) and early antigen (EA). Titers were highest in the patients with more anaplastic nasopharyngeal carcinomas. The skin test and serologic data are consistent with studies in Chinese patients, indicating that NPC in non-Chinese and Chinese patients is biologically similar.

We examined whether any immunoglobulin allotype was associated with an elevated risk of Burkitt's lymphoma because of the association between Burkitt's lymphoma and abnormalities of the immunoglobulin-bearing chromosomes. The distribution of Gm and Km phenotypes among 56 Burkitt lymphoma cases and 25 age-matched controls was unremarkable. Burkitt's lymphoma has also been associated with the Epstein-Barr virus, and we therefore sought a relationship between immunoglobulin allotypes and antibody response to the component antigens of the Epstein-Barr virus, VCA, EA-D, EA-R and EBNA. No immunoglobulin phenotype was associated with higher antibody titers against any antigen, but there appeared to be an interactive effect in which persons homozygous at both Gm and Km loci had elevated titers against several of the component antigens of the Epstein-Barr virus. This is the first report of an interactive effect between immunoglobulin allotypes and viruses. Antibody titers against antigens of the Epstein-Barr virus were higher in cases than in controls, as expected. However, female cases had significantly higher titers than male cases, a finding similar to that previously reported in healthy persons.

We examined the geographic pattern of nasopharyngeal cancer (NP cancer) mortality in the United States using economic sub-regions (ESRs) as the basis for analysis. The distribution of 15,145 deaths from NP cancer over the years 1950-1979 revealed clustering in the 119 ESRs that was not detected in analyses of distribution by the 48 states, 506 state economic areas or 3,056 counties or combinations of counties of the coterminous United States. NP cancer mortality among white males was concentrated on the south-east Atlantic and Gulf coasts. This newly described pattern is not due to any recent changes in mortality rates and should provide leads to further epidemiologic study.

Delayed hypersensitivity reactions to a battery of antigens were measured in 145 Tunisian breast cancer patients to determine whether an immunologic mechanism could be detected which might explain the high frequency (60%) of the rapidly progressing form in Tunisian breast cancer patients. Although a greater proportion (30%) of patients with rapily progressing breast cancer reacted to extracts of a breast tumor antigen (2937) than patients without PEV (9%), no significnat difference between PEV and non-PEV patients could be found in reactivity to DNCB, standard microbial antigens, or extracts from tissue culture cell lines. Rapidly progressing breast cancer in Tunisia is not associated with an impairment of delayed hypersensitivity.

The histological features of 94 cases of carcinoma of the breast seen in Tunisia were recorded and subsequently correlated with the clinical classification of the patients in terms of poussée évolutive (PEV) categories. Histological features analyzed in the breast tissues and skin included tumor type, nuclear grade, number of mitoses, involvement of the dermis, cutaneous inflammatory infiltrate and edema. Twenty-eight percent of the cases in which the skin was examined showed tumor emboli in the lymphatics of the dermis. The frequency of cutaneous permeation correlated with the PEV categories. The percentage of cases with nuclear grade 3 was higher for the group with rapid progression of the disease (PEV 1,2,3) than for the cases belonging to the PEV-0 category (90% versus 64.2%). The present study demonstrates that a large proportion of breast carcinoma patients in Tunisia suffer from "inflammatory carcinoma of the breast".

It has been suggested that poussée évolutive (PEV) or rapidly progressing breast cancer (RPBC) represents a failure in the host immune system to control the proliferation of breast cancer cells. To evaluate this possibility, we have performed in vivo and in vitro assays of cellular immunity in Tunisian patients with breast cancer. Studies of delayed hypersensitivity using microbial antigens and in vitro including lymphocyte transformation tests and measurements of B and T cells indicated that RPBC patients had an immune response comparable to that of breast cancer patients without evidence of rapid progression. Normal Tunisians were more immunocompetent, however, an appeared to have a higher level of immune activity than normal individuals in the United States. In a second, independent series, an increased frequency of blood group A was found in RPBC patients, suggesting a genetic predisposition to this form of breast cancer. However HLA typing for A, B and DRW antigens revealed no specific RPBC-associated HLA antigen. Our studies clearly demonstrate that RPBC, or PEV, is not a reflection of immunodeficiency.

Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease.

Twenty-three patients with recent infectious mononucleosis were studied for cell-mediated immunity to Epstein-Barr virus (EBV)-associated antigens. By means of a virion-containing antigen preparation, (P3J), leukocyte migration inhibition was demonstrated in 6 of 13 patients with acute infectious mononucleosis (IM) and in 6 of 10 patients studied during the convalescent period. Inhibition with a soluble antigen (S) preparation was seen in only a few patients at all stages of the illness. Lymphocyte blast transformation on exposure to P3J occurred in 4 of 9 patients with acute IM; no other study group reacted. Control donors lacking anti-EBV antibodies did not demonstrate migration inhibition or blast transformation with either P3J or S. Control donors with evidence of previous EBV infection did demonstrate migration inhibition with P3J (8 of 12) and S (3 of 10). These studies indicated that cell-mediate immunity to EBV-associated antigens could be detected by either leukocyte migration inhibition or lymphocyte blast transformation, but neither assay is diagnostic of infectious mononucleosis.

One of six white-lipped marmosets inoculated with cell-free B95-8 virus developed diffuse malignant lymphoma. Epstein-Barr virus (EBV) DNA was detected in a pathologically enlarged mandibular lymph node by DNA-DNA hybridization. The affected animal at the time of killing had EBV antibody titers of 1:320 for viral capsid antigen (VCA) and 1:20 for early antigen (EA) while all non-diseased animals had less than or equal to 1:80 VCA antibody and no detectable EA antibody. This is the first report of lymphoma development in a white-lipped marmoset following EBV inoculation.

Epstein-Barr virus nuclear antigen (EBNA) preparations from three sources were tested with sera from normal individuals and patients with Hodgkin's disease, breast carcinoma, Burkitt's lymphoma, and American and Chinese nasopharyngeal carcinoma. Individual sera with discordant antibody patterns were noted in all groups. Sera from both NPC groups gave significantly higher anti-EBNA titers on cell lines converted with P3HR-1 or B95-8 virus compared with anti-EBNA titers on Raji cells. Anti-EBNA titers of Chinese NPC sera showed no correlation among the three EBNA sources, while all other groups had highly correlated titers. Cross-absorption experiments present evidence for more than one antigenic determinant on EBNA. These results suggest an additional parameter for distinguishing Chinese NPC from other EBV-related disorders.

Four-hundred and fifty nine cancer patients were skin tested with extracts from five lymphoid cell lines. More than 50% of patients with lymphoma had positive skin tests with the extracts prepared from the cell line derived from Burkitt's lymphoma (BL) and more than 50% of nasopharyngeal carcinoma (NPC) patients reacted to the NPC-derived cell line extracts. Although the significant association between patient diagnosis and orgin of cell lines suggested that tumor-associated antigens were responsible for the pattern of delayed hypersensitivity, problems in standardization of antigen potency and non-specificity need to be resolved before this in vivo assay achieves its full potential.

The leukocyte adherence inhibition (LAI) assay was utilized as a test for cellular immunity to Epstein-Barr virus (EBV) antigens in 22 patients with infectious mononucleosis (IM), 47 patients with lymphoma, 101 carcinoma patients, and 84 subjects without cancer. Response to EB virion ("v") antigen was generally present at the time of diagnosis in the IM patients but the response to EB soluble ("S") antigen was delayed. An increased CMI response to "v" antigen was found in patients with IM, Hodgkin's disease and non-Hodgkin's lymphoma as compared to controls with and without cancer. Patients with Hodgkin's disease had depressed responses to the EBV-associated "S" antigen. The finding of increased LAI responses to "v" antigen in Hodgkin's disease patients with high EBV antibody titers conflicts with previous reports attributing high antibody responses against EBV to a generalized depressed cell-mediated immunity.

Serial samples of sera from patients with African Burkitt's lymphoma were tested for antibody against Epstein-Barr virus (EBV)-specific membrane antigen (MA) by the antibody-dependent cell-mediated cytotoxicity assay (ADCC). Titers of patients in the long-term survivor group were generally higher than those found in the sera of patients in the short-term survivor group. Although ADCC titers to EBV-MA were not useful in predicting which patients would relapse there was a definite relationship between ADCC titer and prognosis. The individual differences in ADCC titers in patients in remission may explain the variability of responses that have been reported in studies on serotherapy with remission plasma.

One hundred and eighty-five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2-year period, were individually matched with healthy controls of the same age, sex, and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein-Barr viral capsid antierences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL-A antigens, stage of disease and histology did not alter this pattern, except that significant case-control differences in EB-VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB-VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB-VCA and EBV-EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients.

Epidemiologic studies indicate that human T-cell lymphotropic virus type I (HTLV-I), the causative agent of most cases of adult T-cell leukemia/lymphoma (ATLL) in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large-scale serosurvey was undertaken to improve our understanding of HTLV-I prevalence in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locales worldwide; 76% of these sera came from clinically healthy donors. Samples were initially screened by an enzyme-linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age-sex difference was observed between populations in the Caribbean and non-endemic regions of Japan. The reason for the male excess in non-endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLV-I-endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV-I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub-Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross-reacting antibodies. No pattern was detected that could explain the cross-reactivity solely on the basis of geographic areas, specific patterns of non-viral parasitic infection, or methods of handling the specimens. It is possible that these cross-reactivities are antibodies to proteins from HTLV-I-related retroviruses yet to be discovered.

The prevalence of antibodies against the newly described human T-cell lymphoma virus, type I (HTLV-I) in two communities in Ghana, West Africa, is described. There was no difference by community (urban, 3.6% and rural, 4.0%). Prevalence increased with age, being 5.9% among persons greater than 10 years old, but did not differ by sex. There was no difference when data were analysed by housing status or crowding. Non-confirmed reactions in the assay system were frequent and correlated with both prevalence and titer of antibody against malaria. Possible explanations include vector-borne transmission like that of malaria, but the relationship is more probably due to a polyclonal stimulation of B cells, enhancing the potential for detecting reactivity in the assay. Because assay systems vary and because most laboratories do not routinely use a confirmation assay, results presented by different groups must be interpreted cautiously.

This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.

Demographic and pathologic information on over 1,000 newly diagnosed patients with nasopharyngeal carcinoma was obtained from population-based registries in the United States. Age-adjusted incidence rates were similar for whites and blacks and both were significantly lower than for Chinese Americans. Age-related differences in cell type were observed in white NPC patients, lymphoepithelial carcinomas having a younger age distribution than either squamous-cell or transitional-cell carcinomas. Mortality rates for nasopharyngeal cancer were substantially lower than incidence rates for nasopharyngeal carcinoma, but both indices revealed a minor peak in rates among teenaged whites and blacks. The five-year survival rate for nasopharyngeal carcinoma was less than 25% and has not changed in recent years. Prognosis was better for females and for young patients. Despite the difficulties in obtaining uniform pathologic classification in such a large study, the interrelationship between pathologic subtype of nasopharyngeal carcinoma and demographic features emphasizes the need for adherence to a more uniform histologic classification.