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Biomedical subjects

G Henle

Publications and source records attributed to G Henle.

At least 91 records · Page 5Linked to original sources

Heterophil antigen in bovine sera detectable by immune adherence hemagglutination with infectious mononucleosis sera.

Bovine sera for tissue culture use were shown to contain heterophil antigen of the Paul-Bunnell-Davidsohn type by immune adherence hemagglutination tests with sera from patients with infectious mononucleosis. The antibody titers observed were comparable to those determined by two other methods; i.e., the immune adherence hemagglutination test was found to be as specific as the differential absorption test with horse erythrocytes or the ox cell hemolysis assay,but it appeared to be the most sensitive of the three procedures. All 16 individual or pooled bovine serum samples showed Paul-Bunnell-Davidsohn antigen at concentrations varying over a fourfold range. The potential usefulness of the immune adherence hemagglutination test for various Paul-Bunnell-Davidsohn antigen-related problems and implications of the observations are discussed.

Animals↗

A cluster of Epstein-Barr-virus-associated American Burkitt's lymphoma.

We investigated four patients in whom histologically confirmed Burkitt's lymphomas developed during a one-year period. They were young adults living within 50 km of each other in a rural area of Pennsylvania. Two patients were related by marriage, but there was no contact with or between the other two. Although the majority of American Burkitt's lymphomas are not associated with the Epstein-Barr virus, all four patients showed spectra and titers of antibodies to antigens related to that virus that were characteristic of virus-associated Burkitt's lymphoma in Africa. Viral DNA and numerous cells with virus-determined nuclear antigen were found in tumor specimens available from three patients. These cases are unusual, since time-space clustering of Burkitt's lymphoma associated with Epstein-Barr virus has been observed thus far only in Africa.

Adult↗

Transformation of lymphocytes by Herpesvirus papio.

Cotton-topped (CT) or white-lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP-transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and/or to EBV-induced early antigens (EA). None of 12 WL LCL revealed such antigen-producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV-specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X-irradiated HVP or EBV-carring cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA-positive, but no EBNA-positive cells. Nuclear antigens were undetectable also with anti-VCA-positive sera from baboons, chimpanzees, or other non-human primates. DNA-complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1-2 virus genome equivalents per cell, while at least 12-25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA-DNA reassociation kinetics.

Animals↗

Infectious mononucleosis in children. Evaluation of Epstein-Barr virus-specific serological data.

Epstein-Barr virus (EBV)-specific antibody responses were determined in 43 consecutive pediatric patients who had signs and symptoms of inectious mononucleosis (IM) and positive diagnostic tests for mononucleosis (Monspot). Thirty patients gave clear-cut serologic evidence of primary EBV infections; of the remaining 13 patients, seven had no antibodies to EBV in the acute- or convalescent-phase sera and six showed serologic patterns of past EBV infections. Further testing proved that the initial Monospot results were either false-positive or were incorrectly interpreted in all 13 patients with unidentifiable illnesses but in only two of the patients with current EBV infections. The data confirm the occurrence of classical IM in children and show that the disease and the EBV-specific antibody responses can be virtually indistinguishable from adult cases.

Adolescent↗

Evidence for an etiologic relation of the Epstein-Barr virus to human malignancies.

Studies on virus-induced animal tumors have provided indirect approaches to a search for viruses causing human malignancies. Epstein-Barr virus (EBV), the cause of infectious mononucleosis, served to illustrate the usefulness of these approaches in linking EBV with Burkitt's lymphoma and nasopharyngeal carcinoma. Despite its demonstrated intimate association with these tumors the role of EBV in their causation remains uncertain. While a passenger role seems excluded, it cannot be decided whether EBV is the primary or a secondary agent in the etiology of the tumors. If the primary cause, immunologic, genetic, virologic or other environmental factors are undoubtedly needed for EBV to express its obvious oncogenic potential. The data illustrate the difficulties encountered in proving a viral etiology of human malignancies.

Antibodies, Viral↗

Late persistence of serum gamma-glutamyl transpeptidase activity after mononucleosis. Report of 3 cases.

gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown.

Adult↗

Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes.

Cold agglutinins (CA) were evaluated prospectively in patients with various mononucleosis syndromes and in a large control group. Cold agglutinins with anti-i specificity were seen mainly in heterophil-positive or -negative Epstein-Barr virus (EBV)-induced infectious mononucleosis (31.8% of cases). Unclassified CA with equal reactivity against cord and adult erythrocytes were seen in 56 of 150 (37.3%) cases of heterophil-antibody-positive infectious mononucleosis (IM), in 1 of 7 (14.3%) cases of heterophil-negative EBV-induced IM, and in 12 of 31 (38.7%) cases of the heterophil-negative mononucleosis-like syndrome due to cytomegalovirus or other unspecified agents. One patient with heterophil-positive IM had a persistent, partially papain sensitive CA with anti-Pr-like activity. Anti-i CA were seen in less than 1.0% of healthy young adults (500) or patients without mononucleosis (500) submitted for heterophil studies. Unclassified CA were noted in 3.2% of the latter 1000 samples.

Agglutinins↗

Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma.

Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV-induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV-specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2-6 years after initial therapy had only low levels of EBV-specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA-specific IgA and even fewer EA-specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA- or D-specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV-specific antibodies. Possible reasons for this unique response in NPC have been discussed.

Animals↗

Clinical and laboratory evaluation of elderly patients with heterophil-antibody positive infectious mononucleosis. Report of seven patients, ages 40 to 78.

Clinical, hematologic, biochemical and serologic data are recorded in seven patients aged 40 to 78 years with heterophil-antibody positive infectious mononucleosis (HA+IM). Clinical observations included fever of 22 to 30 days' duration (five of seven patients), sore throat (six of seven patients), myalgia (five of seven patients) and prominent lymph adenopathy (two of seven patients). Initial blood smears revealed significant numbers of atypical lymphocytes in only five of seven patients; however, or serial testing, in the remaining two patients Downey cells developed to a degree seen in most young adult patients with infectious mononucleosis. Comparison of liver function data from these and younger patients suggests that abnormalities tend to be more marked in those in the older than in those in the younger age range. Serologic tests confirmed primary Epstein-Barr virus (EBV) infections in all seven patients based on detection of IgM antibodies to EB viral capsid antigen in specimens obtained early, but not late, in the course of the infection, transitory antibody responses to the D (diffuse) component of the EMB-induced early antigen complex, and the initial absence and later development of antibodies to the EBV-associated nuclear antigen. Thus, the serologic data did not differ from those seen in younger patients. These results show that infectious mononucleosis should be included in the differential diagnosis of fever, sore throat and myalgia with or without significant cervical adenopathy in elderly persons.

Adolescent↗

Surface marker characteristics and Epstein-Barr virus studies of two established North American Burkitt's lymphoma cell lines.

Tumor cell lines have been established in continuous culture from two North American Burkitt's lymphomas. The SU-AmB-1 line, derived from a patient with low serum antibody titers to Epstein-Barr virus (EBV), was devoid of EBV genomes by the reaction for EBV-associated nuclear antigen (EBNA), could not be induced to express EBV antigens, and was highly refractory to EBV superinfection. Conversely, the SU-AmB-2 cell line, derived from a patient with "African type" serology, yielded a positive EBNA reaction and was readily inducible and superinfectable. Although both cell lines possessed B (bone-marrow-derived) cell characteristics, they had different surface marker patterns. It is postulated that two different classes of undifferentiated B cell lymphomas exist, one of which is positive for the presence of EBV genomes and occurs endemically in Africa and New Guinea and sporadically in other parts of the world, the other of which is EBV-negative and occurs sporadically throughout the world, including the endemic areas.

Adolescent↗

Burkitt's lymphoma: its clinical course in relation to immunologic reactivities to Epstein-Barr virus and tumor-related antigens.

In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen.

Antibodies, Viral↗

An outbreak of infectious mononucleosis among the personnel of an outpatient clinic.

During a four-week period, nine current or recent primary Epstein-Barr virus (EBV) infections were identified among 29 staff members of an obstetrics and gynecology outpatient clinic of an air force base hospital by EBV-specific serologic tests; i.e., early detection of IgM antibodies to EB viral capsid antigen (VCA), high titers of IgG antibodies to VCA, presence of antibodies to the D (diffuse) component of the EBV-induced early antigen (EA) complex and initial absence and later development of antibodies to the EBV-associated nuclear antigen (EBNA). Five of these individuals showed classical signs and symptoms of infectious mononucleosis (IM) so that the ratio between overt and silent infections was 1.25:1. All but one of these nine individuals gave positive monospot reactions. Three additional staff members were reported to be monospot-positive, of whom two, with prior histories of IM, had IM-like illnesses during the study period but the results of EBV-specific serologic tests were indicative of infections in the past. The EBV infections were limited to the nurses, corpsmen and administrative personnel, of whom none remained susceptible (antibody negative). The virus did not spread to the medical staff although two of the residents had no antibodies to EBV. The data indicate that under some circumstances IM may be more contagious than usually observed.

Adult↗

The specificity of heterophil antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis.

Over several years sera were collected from 14 heterophil-positive students or patients who did not fulfill minimal hematologic criteria for infectious mononucleosis (I.M.) The specificity of these heterophil reactions for I.M. was investigated by determining antibodies to Epstein-Barr virus-determined antigens, i.e., to viral capsid antigens (VCA), early antigens (EA), and EBV-associated nuclear antigens (EBNA). On the basis of detectable anti-EA and/or the early absence and late emergence of anti-EBNA, four of these 14 individuals showed evidence of a current or very recent primary Epstein-Barr virus infection. The other ten patients showed antibody patterns indicative of Epstein-Barr virus infections in the past, and no firm conclusions could be drawn with regard to the specificity of their heterophil reactions. It was assumed, however, that some represented atypical clinical forms of EBV infection and that timing of specimen collection was a factor in explaining the paucity of Downey cells. In three patients, the absorbed heterophil-positive reactions persisted with little change in titer for at least 22 mo and thus might represent false-positive tests.

Adolescent↗