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Biomedical subjects

W Henle

Publications and source records attributed to W Henle.

At least 145 records · Page 8Linked to original sources
PubMed1977

[Factors involved in the development of human tumors using the Epstein-Barr virus as an example (author's transl)].

Several viruses induce tumors in animals under experimental or natural conditions. It is likely therefore that some human malignancies are also caused by viruses. Proof of this hypothesis can be provided only by indirect evidence based on the following criteria: (1) detection of viral antigens or viral genetic information in a given tumor; (2) transformation of normal human cells by the virus in tissue culture; (3) induction of tumors in animals by the virus; and (4) demonstration of enhanced titers of antibodies to the virus in patients bearing the tumor. These criteria have been fulfilled to support a causal relationship of the Epstein-Barr virus (EBV) in Burkitt's lymphoma and nasopharyngeal carcinoma. It is clear, however, that factors of a genetic, immunologic or environmental nature must play an additional role because EBV, the cause of infectious mononucleosis, is widely disseminated yet development of the tumors is a rare event.

Adult↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum antibody responses, demonstration of viral DNA, and characterization of viruses.

6 of 20 cotton-top tamarins (Saguinus oedipus) inoculated with Epstein-Barr virus (EBV) developed diffuse malignant lymphoma resembling reticulum cell or immunoblastic sarcoma of man. Hyperplastic lymphoreticular lesions were induced in three additional animals; in two instances the hyperplastic lesions regressed. Inapparent infection with development of antibody occured in eight animals. In two animals there was no evidence of EBV infection. One animal died in the first week after inoculation of parasitic infection. 10 animals uninoculated or mock-inoculated developed neither lymphoproliferative disease nor antibody. The malignant lymphoma appeared to arise from a cell with an uncleaved vesicular nucleus found in the center of the germinal follicle. The prominent cytologic features of this cell were extensive formation or rough endoplasmic reticulum and elaboration of the cytoplasmic membrane with microvilli. Cell lines derived from these tumors did not have receptors for complement. IgFc, or sheep erythrocytes, and the cell lines adhered to glass and plastic. EB nuclear antigen was found in imprints of two lymph nodes, one with lymphoma and one with hyperplasia. EB virus DNA was detected directly in the tumors of three animals and in cell lines from two lymphomas. Typical herpes virus particles were found in supernatant fluids from cell lines obtained from lymph nodes with tumors and hyperplasia, as well as in lines derived from blood leukocytes of marmosets with inapparent infection. These virus preparations had the biologic property characteristic of EBV, namely, stimulation of cellular DNA synthesis and immortalization of human lymphocytes. The virus derived from two cell lines was neutralized by reference human sera with EBV antibody and not by antibody-negative human sera. The virus derived from the experimental lesions is thus indistinghishable from human EBV. The marmoset has enhanced susceptibility to oncogenesis by EB virus. Among identified factors which may play a role in the heightened tumorigenicity of EB virus in this species are the increased production of virus by transformed cells and the absence of membrane receptors for complement or IgFc on transformed cells.

Animals↗
PubMed1977

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↗
PubMed1977

Enhanced oncogenic behavior of human and mouse cells after cellular hybridization with Burkitt tumor cells.

Studies were made of the expression of the Epstein-Barr virus (EBV) in somatic hybrids of Burkitt tumor cells and human or mouse cells to determine whether EBV genetic information associated with the capacity to transform leukocytes of human and non-human primates could be maintained and expressed in nonlymphoblastoid cells. Data obtained thus far suggest that at least one characteristic associated with cellular transformation (loss of contact inhibition) is expressed only in nonlymphoblastoid cells in which the EBV genome is maintained. In addition, we have demonstrated that human epithelial/Burkitt hybrid cells (D98/HR-1 and D98/Raji) are more oncogenic in nude (athymic) mice than are cells of the human epithelial parental line, D98, or one of the Burkitt lymphoblastoid parent cell lines (Raji); the HR-1 Burkitt parent cell line was as oncogenic as the hybrid cell lines but the time required to induce tumors was much longer. Thus, human epithelial cells show alteration of growth properties in vitro and in vivo after cellular hybridization with Burkitt tumor cells.

Animals↗
PubMed1977

Antibodies to the R component of Epstein-Barr virus-induced early antigens in Burkitt's lymphoma exceeding in titer antibodies to Epstein-Barr capsid antigen.

African patients with Burkitt's lymphoma (BL) may show antibodies to the R (restricted) component of the Epstein-Barr (EB) virus-induced early antigens that appear to match in titer the antibodies to EB viral capsid antigen (VCA) as determined with the aid of acetone-fixed smears of EB3 cells. Virus-producing EB3 cells, however, contain the R component as well as VCA so that the correct anti-VCA titers in such cases remain in doubt. Since the R component, but not VCA, was found to be denatured by methanol fixation, the parallel use of acetone- and methanol-fixed EB3 cell smears permitted the determination of the correct anti-VCA titer. Our results showed that the anti-R titers of BL patients can in fact be up to eightfold higher than the anti-VCA titers. Anti-R titers equaling or exceeding anti-VCA titers have been encountered thus far only in BL.

Acetone↗
PubMed1977

Epstein-Barr virus genome studies in Burkitt's and non-Burkitt's lymphomas in Uganda.

Burkitt's lymphoma (BL) has been widely investigated and has attracted attention because of the possible etiologic role of the Epstein-Barr virus (EBV). To further determine the role of EBV in the causation of this tumor, we measured EBV-specific nuclear antigen (EBNA) and EBV DNA using immunofluorescence and nucleic acid hybridization techniques, respectively. Of 34 BL biopsies, 27 tissues (79%) were EBNA-positive, whereas none of the 25 non-BL biopsy tissues were EBNA-positive. Of 15 BL tumors tested, 14 (93%) were EBV DNA-positive with a mean of 39 (range, 8-86) EBV genome equivalents per cell. Each of the 15 non-BL biopsy specimens subjected to nucleic acid hybridization had less than two virus genome equivalents per cell, although all had serologic evidence of past EBV infection. The findings further supported the possible etiologic role of EBV in African BL and negated the passenger hypothesis. The EBV genome could, therefore, be used as a separating marker between African BL and non-BL lymphomas.

Adolescent↗
PubMed1977

Primary Epstein-Barr virus infection in a renal transplant recipient.

A young girl with familial nephronophthisis and chronic renal failure contracted a primary Epstein-Barr virus infection after renal transplantation. During the illness she developed a clinical picture of fever and pneumonitis which closely resembled the posttransplantation syndrome usually associated with cytomegalovirus, although she had no evidence of cytomegalovirus infection. A younger sibling with the same renal disease was found retrospectively to have apparently had an earlier subclinical Epstein-Barr virus infection.

Antibodies, Viral↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

Anti-EBV antibody titers in non-Hodgkin lymphomas.

Antibody titers to Epstein-Barr virus (EBV)-related antigens, i.e. viral capsid antigen (VCA), the D and R components of the early antigen (EA) complex and the EBV-associated nuclear antigen (EBNA), were determined in a series of 86 patients with non-Hodgkin lymphomas and in 150 matched control subjects. The lymphoma patients belonged to four histological groups: diffuse, nodular, hyperbasophilic malignant lymphoma (HML) and unclassified. The EBV-related serological data were compared to the incidence of antibodies to other herpes viruses, i.e. cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella zoster virus (VZV), and correlated with immune disorders, which are particularly frequent in the HML type of lymphoma. The results revealed a significantly higher incidence of anti-EA-D titers in lymphoma patients and slight but significant increases in the geometric mean anti-VCA titers in the HML and unclassified group of patients. These elevated anti-EBV titers in patients were not associated with an increase in titres of antibodies to other herpes viruses. They did not correlate with the signs of immune deficiency observed or with the incidence of auto-antibodies.

Adolescent↗
PubMed1976

Detection of Epstein-Barr virus DNA in American Burkitt's lymphoma.

Twenty American patients with Burkitt's lymphoma (BL) were studied serologically and biochemically to detect an association with Epstein-Barr virus (EBV). A wide range of antibody reactivities was encountered. Five patients had serological profiles similar to those of African patients with BL: one and possibly two of these patients harbored EBV-DNA in their tumors. Fifteen patients had low or absent antibody to EBV: tumors from 10 of these patients lacked evidence of EBV-DNA. An unexplained association between elevated antibody (greater than or equal to 1:80) to EBV virus capsid antigen (VCA) and a favorable prognosis was noted in this series; this prognostic observation requires further substantiation. Thus, it appears that EBV-associated BL is inversely proportional to tumor endemicity. An etiological role for EBV in BL remains speculative.

Adolescent↗
PubMed1976

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↗
PubMed1976

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↗