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Biomedical subjects

W Henle

Publications and source records attributed to W Henle.

At least 91 records · Page 5Linked to original sources

Detection of infectious mononucleosis heterophil antibody by a rapid, standardized enzyme-linked immunosorbent assay procedure.

A rapid, specific, sensitive, standardized, a reproducible enzyme-linked immunosorbent assay (ELISA) procedure has been developed for detecting the heterophil antibody associated with infectious mononucleosis (IM). The IM heterophil antibody used for the solid phase was purified from bovine erythrocyte stroma. The test uses heavy-chain-specific anti-immunoglobulin M (IgM) labeled with alkaline phosphatase and three 10-min incubations. The quantitative results correlated well with horse erythrocyte agglutination titers. Absorption tests confirmed the specificity of the ELISA reactions for IM heterophil antibodies. Neither very high levels of IgM in myeloma sera nor high levels of rheumatoid factor caused false-positive reactions. A number of probable IM cases were encountered which positive by ELISA but negative by the horse erythrocyte slide agglutination test. Absorption studies indicated that these were true-positives for the IM heterophil antibody. The IM heterophil antibodies were confirmed to be predominantly of the IgM class, but moderate proportions of the IgM class were sometimes encountered.

Antibodies, Viral↗

Association of Epstein-Barr virus with nasopharyngeal carcinoma in Alaskan native patients: serum antibodies and tissue EBNA and DNA.

Biopsy specimens from Alaskan Native patients with nasopharyngeal carcinoma (NPC) and from other patients seen on the otolaryngology service were tested for Epstein-Barr virus-specific DNA and nuclear antigen (EBNA). Serum samples from both groups were tested for various EBV-related antibodies. EBV DNA and EBNA results were in agreement in 29 of 31 tissue specimens tested by the two methods. Ten of 11 biopsies containing NPC cells were positive for EBV DNA. Two NPC patients had biopsies that showed only atypical epithelium but were also positive for EBV DNA or EBNA. The other tissue specimens were negative except for biopsies from two patients: one with a parotid gland lymphoepithelial lesion; another with undifferentiated carcinoma of salivary gland origin.

Alaska↗

Malaria, sex, and place of residence as factors in antibody response to Epstein-Barr virus in Ghana, West Africa.

Both Epstein-Barr virus and malaria have been implicated as possible factors in Burkitt's lymphoma. To examine this implication a cross-sectional serological survey of an urban and a rural population in Ghana was conducted. Malaria was more prevalent in the rural areas, but there was no difference in antiviral capsid antigen (VCA) antibody titres between urban and rural dwellers. There was also no correlation between anti-malaria antibody titres and anti-VCA antibody titres. Thus malaria does not seem to influence immunological response to Epstein-Barr virus infection, as measured by anti-VCA antibodies. These results suggest that if Epstein-Barr virus infection and malaria are important in the aetiology of Burkitt's lymphoma, they produce their effects independently. The survey also showed that those in rural areas seroconverted earlier than those in urban areas, and that antibody levels were consistently higher in females than in males in every age-group. Case-control studies and screening programmes involving anti-VCA levels will therefore have to take these two findings into account.

Antibodies, Viral↗

Epstein-Barr-virus-carrying lymphoma in a patient with ataxia-telangiectasia.

An undifferentiated lymphocytic lymphoma of mesenteric lymph nodes occurred in a young boy with ataxia-telangiectasia. Two independent tests, Epstein-Barr virus (EBV)-cRNA/DNA hybridisation and EBV DNA/DNA reassociation kinetic analysis, showed 53 and 68 EBV genome equivalents per cell respectively, which was compatible with an EBV-genome-carrying tumour. Whether this was a polyclonal lymphoproliferation or a monoclonal tumour could not be determined owing to lack of suitable material. The presence of EBV genomes should be sought in lymphomas arising in ataxia-telangiectasia and other immunodeficiencies.

Abdominal Neoplasms↗

Expression of Epstein-Barr viral early antigen in monolayer tissue cultures after transfection with viral DNA and DNA fragments.

Antigens associated with the Epstein-Barr virus (EBV) replicative cycle were found in the nucleus and cytoplasm of human placental, Vero, BSC-1, and owl monkey kidney cells transfected with EBV DNA prepared from several different strains of virus. The number of antigen-positive nuclei increased when transfection was followed by cell fusion induced by inactivated Sendai virus. About 1,200 antigen-positive foci were induced per micrograms of EBV DNA. On the basis of their reactivity with various well-characterized human sera, it appears that the antigens are part of the early antigen complex. None of the four restriction endonucleases, EcoRI, HindIII, SalI, and BamHI, destroyed the ability of EBV DNA to induce early antigen. However, only SalI seemed to leave intact the full spectrum of antigen expression by the HR-1 and FF41 strains of EBV DNA. By means of transfection with recombinant DNA plasmids containing different EBV (FF41) DNA fragments regenerated by EcoRI, we showed that the coding region for early antigen was at least partially contained on the 17.2-megadalton EcoRI B fragment.

Animals↗

Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis.

The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (>/=320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (>/=10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels of antibody to the EBV-associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive RA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA-associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of EBV-specific antibodies were studied serially over a period of 6-10 mo in patients with RA and OA. Parameters of disease activity were determined and compared to antibody levels. EBV-specific antibodies in sera of OA patients remained constant and within normal limits throughout the study. Although EBV-specific antibodies were often elevated in RA patients, they also remained constant, with the exception of three patients, who showed gradual increases in one of the four antibodies, which did not correlate with disease activity.

Adolescent↗

Cellular immune defects to Epstein-Barr virus-determined antigens in young males.

Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.

Adolescent↗

Very late relapses in patients with Burkitt's lymphoma: clinical and serologic studies.

Of 117 patients in remission for at least 12 months after chemotherapy for confirmed Burkitt's lymphoma, 14 subsequently relapsed. Frequency of ever relapsing in this group varied from 12% 2 years after chemotherapy to 3-8% 3-6 years after chemotherapy. Risk of very late relapse (VLR) increased with the occurrence of meningeal disease and/or relapse before a remission of 12 months or more was achieved. The use of combination chemotherapy and especially prophylactic intrathecal methotrexate significantly lowered the risk of VLR (P less than 0.03). Serial testing for antibodies to Epstein-Barr viral capsid antigen to the diffuse and restricted components of the early antigen complex and to the Epstein-Barr virus-specific nuclear antigen revealed minor fluctuations but no consistent increases in antibody titers preceding detection of VLR. The serologic follow-up tests thus were not clinically useful for prediction of the imminence of a recurrence. Patients developing VLR generally maintained moderate-to-high titers of antibodies to restricted or diffuse components throughout the long remission periods, which indicated that they were not beyond the danger of a relapse at an unspecified time in the future.

Adolescent↗

Epstein-Barr virus-specific serology in immunologically compromised individuals.

Since B-lymphocytes are targets and a continuing habitat of Epstein-Barr virus (EBV) and the cell-mediated immune system becomes secondarily involved, one may anticipate that primary and persistent EBV infections in immunologically compromised individuals take unusual courses. Depending on the immunological defect, the clinical, hematological, and serological responses to primary EBV infections may be more or less pronounced than in immunologically competent patients. Infectious mononucleosis has per se an immunosuppressive effect which may enhance a preexisting immune defect. The persistent latent viral carrier state which regularly ensues after the primary EBV infection may become decontrolled by immunosuppressive diseases or therapy, leading rarely to illnesses referable to the virus but often to increases in the titers of antibodies to viral capsid and early antigens and/or declines in the antibody titer to EBV-associated nuclear antigen. Absence or dysfunction of different leukocyte subpopulations may account for the differential changes in antibody patterns.

Animals↗

Fatal Epstein-Barr virus infection in a child with acute lymphoblastic leukemia in remission.

A 9-year-old white boy developed a fatal primary Epstein-Barr virus (EBV) infection while receiving chemotherapy for acute lymphoblastic leukemia in remission. Histopathological findings at the height of the proliferative phase of the illness were compatible with a virally induced hemophagocytic syndrome. The infection spontaneously converted to complete aplasia of the bone marrow and lymph nodes. Serological studies disclosed that the patient had no antibodies to EBV prior to the infection, but during the acute phase he showed a spectrum and titers of antibodies to EBV-specific antigens characteristic of a current primary EBV infection. A lymph node biopsy obtained 5 weeks after onset revealed Epstein-Barr nuclear antigen in approximately 50% of the cells. The boy's condition deteriorated rapidly, with disseminated candidiasis resulting in cardiorespiratory failure and death. Lymph nodes obtained at autopsy no longer contained Epstein-Barr nuclear antigen-positive cells.

Animals↗

Cell-mediated immune reactions in three patients with malignant lymphoproliferative diseases in remission and abnormally high Epstein-Barr virus antibody titers.

Two patients with Hodgkin's disease in remission and one chronic lymphatic leukemia patient with extraordinarily high anti-Epstein-Barr virus (EBV) (viral capsid antigen) antibody titers (greater than 10,000) were selected to study a spectrum of cell-mediated immune responses, including natural killer, interferon-boosted killer, antibody-dependent lymphocytotoxicity, and T-cell-mediated reactions. The purpose was to compare these reactions in patients with immunosuppression and a high EBV load who can hold their EBV-carrying cells under control with the corresponding reactions in patients with EBV-carrying lymphoproliferative disease. In contrast to the latter group, the three patients of the present study showed a less profound and less general suppression of the immune responses. Multiple effector mechanisms probably safeguard against the proliferation of EBV-transformed B-cells. Clinically manifest EBV-carrying lymphoproliferative disease occurs only in very severe immunodeficiencies effecting multiple effectors.

Adolescent↗

The reliability of IgA antibody to Epstein-Barr virus (EBV) capsid antigen as a test for the diagnosis of nasopharyngeal carcinoma (NPC).

Since patients with nasopharyngeal carcinoma were first reported to have elevated levels of IgA antibody to Epstein-Barr virus (EBV) in their sera, workers in a number of countries have studied the possibility that this assay could be used in the diagnosis and monitoring of patients with this disease. In the United States, a collaborative project involving seven centers has been established to investigate the potential value of IgA antibody to EBV viral capsid antigen (VCA) as a clinical tool. In this report, we will summarize the results obtained from three studies: a comparison of EBV serology in three laboratories; a retrospective study of 37 nasopharyngeal carcinoma (NPC) patients and controls, and a prospective study of 126 NPC patients and 683 controls, including 149 patients with other malignancies involving the head and neck. The study of testing comparability in three laboratories demonstrated the feasibility of using this assay in a number of laboratories. The retrospective study confirmed the difference in IgA antibody titers between NPC patients and matched controls. The prospective study showed a relationship between IgA antibody titers and histopathology but not disease stage. IgA antibody titers were elevated more frequently in patients with nonkeratinizing or poorly differentiated types of NPC than for the well-differentiated squamous cell carcinomas. While IgA antibodies to EBV VCA appear to be of value in the early detection and diagnosis of NPC, it is possible that additional serologic tests for immunity to EBV, such as IgG antibody to VCA or early antigen (EA), will improve even further the clinical value of EBV serology in the management of NPC.

Antibodies, Viral↗

Nasopharyngeal carcinoma in Alaskan Eskimos Indians, and Aleuts: a review of cases and study of Epstein-Barr virus, HLA, and environmental risk factors.

The records of thirty-one patients with nasopharyngeal carcinoma (NPC) diagnosed from 1966 through 1976 among the Alaskan native population (Eskimo, Aleut, Indian) were reviewed. There were 25 males and six females, which results in relatively high incidence rates per 100,000 of 13.5 for males and 3.7 for females. Clinical and pathologic features were similar to those found among southern Chinese NPC patients. Five-year survival rate was 48%. Antibodies to Epstein-Barr virus were higher in NPC patients than in patients with other tumors or matched controls. On histocompatibility testing Sin-2 was not detected, nor was there significantly increased frequency of A2. Instead, BW40 and a second locus blank occurred more often among NPC patients than among other groups. In response to a questionnaire, NPC patients more often reported use of salt fish in the childhood diet, smoking of cigarettes, and exposure to noxious inhalants than did controls, but the differences were not statistically significant.

Adult↗

Prognostic factors in Burkitt's lymphoma: importance of total tumor burden.

In 42 patients with African Burkitt's lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti-EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlated with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitt's lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti-EA titer.

Adolescent↗

Epstein-Barr virus-specific antibody titers in seven Alaskan natives before and after diagnosis of nasopharyngeal carcinoma.

Results are presented of Epstein-Barr virus-specific serologic tests for seven Alaskan Native patients with nasopharyngeal carcinoma (NPC) from whom serum had been collected 2-10 years before diagnosis and up to 6 years after diagnosis. The pre-illness antibody spectra and titers of the NPC patients did not differ from those of controls. However, broadened antibody spectra and elevated titers were associated with the emergence of NPC disease, which in one case was present as early as 22 months before actual diagnosis. Increasing or continuously high antibody titers were associated with progression of the disease and death, whereas patients who maintained relatively low, stable antibody titers after treatment have remained well.

Adenoma, Pleomorphic↗