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Biomedical subjects

W Henle

Publications and source records attributed to W Henle.

At least 163 records · Page 9Linked to original sources

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↗

Encephalitis in infectious mononucleosis: diagnostic considerations.

Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection.

Adolescent↗

Antibody patterns to herpesviruses in kaposi's sarcoma: serological association of european kaposi's sarcoma with cytomegalovirus.

Sera from patients with Kaposi's sarcoma (KS) were examined for antibody titres to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) types 1 and 2 by four techniques: indirect haemagglutination (IHA), complement fixation (CF), virus neutralization (NT) and indirect immunofluorescence (IF). The patients were classified, according to the stage of disease, as progressive and regressive. Control sera were obtained from healthy adults, matched for age, sex, race, socioeconomic status and geographic location, as well as from patients with melanoma, some of whom were receiving chemotherapy similar to that given to the KS patients. All KS sera contained CMV-neutralizing antibodies. Seventy-five percent of the European KS patients, mainly regressors, showed elevated anti-CMV titres by IHA with a significant increase in the geometric mean over the corresponding healthy adult group and the melanoma group. An overrepresentation of high anti-CMV titres, although less marked, was found by CF. There was no significant association with antibodies to EBV, HSV-1 and HSV-2 related antigens. By contrast, the African KS patients, mainly progressors, did not show a serologic association with CMV or with EBV and HSV-1 and 2. The implication of these results is discussed.

Adult↗

Primary Epstein-Barr-virus infections in acute neurologic diseases.

Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

Acute Disease↗

Attempts to detect virus-specific DNA sequences in human tumors. III. Epstein-Barr viral DNA in non-lymphoid nasopharyngeal carcinoma cells.

Fourteen tumors of the nasopharyngeal region were analyzed for the presence of Epstein-Barr virus-specific DNA by DNA-cRNA hybridization. These data were compared to the histology of the respective tumors and the seroreactivity of the tumor-bearing patient against EBV-related antigens. With one exception, all tumor pieces containing nasopharyngeal carcinoma cells hybridized significantly with EBV-cRNA. Tumors of predominantly epithelial morphology annealed in the highest range. In situ-hybridization of freeze sections from a tumor containing almost equal amounts of tumor cells and lymphocytes revealed hybridizing DNA within nuclei of non-lymphoid cells. Although these data do not exclude the presence of EBV-DNA within lymphoid cells, they clearly demonstrate that in nasopharyngeal carcinomas the vast majority of EBV-specific DNA rests within non-lymphoid cells.

Carcinoma↗

Clinical evaluation of patients with infectious mononucleosis and development of antibodies to the R component of the Epstein-Barr virus-induced early antigen complex.

Previous reports have emphasized that the transitory antibody responses to Epstein-Barr virus (EBV)-induced early antigens (EA) in the course of infectious mononucleosis are usually directed against the D (diffuse) component of the EA complex. In this report clinical and serologic data have been presented on 14 patients with infectious mononucleosis who responded either solely with antibodies to the R (restricted) component of the EA complex or revealed anti-R after the initial anti-D responses had subsided weeks or months after onset of the disease. Anti-R persisted usually for many months , as many as 39, but in some patients it was no longer detectable in late follow-up serum spectimens. Although many patients had an unremarkable course of illness, others, mostly those with late anti-R responses, showed unusual or protracted clinical manifestations and several complained over periods of 4 to 28 months of recurrent symptoms resembling those experienced during the acute stage of disease. The presence of anti-R and the relatively high continuous titers of antibodies to EB viral capsid antigens (VCA) may reflect a more than usual, persistent EBV activity which, in turn, may account for the recurrent symptoms.

Adolescent↗

Seroepidemiologic study of Epstein-Barr virus infections in a rural community.

The prevalence and titers of antibodies to capsid antigens of Epstein-Barr virus ad to the diffuse and restricted components of the Epstein-Barr virus-induced early antigen complex were determined in 109 families of a semirural community in Louisiana. Titers of antibody to the capsid antigens larger than or equal to 10 were found in 84 percent of children aged two to five years, and the prevalence increased with age to nearly 100 percent. There was a positive but variable correlation of the prevalence of anti-capsid antigen reactivity with low socioeconomic status and crowding. An overrepresentation of high titers of antibody to capsid antigens was present in individuals with a past history of pneumonia and urinary tract infections. The geometric mean titers of antibody to capsid antigens were highest in early childhood, lowest in adolescence and young adulthood, and high in the elderly. Females in all age groups and tonsillectomized children showed a higher geometric mean titer than their male and nontonsillectomized counterparts, respectively. Antibodies to the early antigen complex were found rarely (8.2 percent) and only in sera with relatively high titers of antibody to capsid antigens.

Adolescent↗

Epidemiology of cytomegalovirus infection after transplantation and immunosuppression.

Viral infections and clinical complications were studied during hemodialysis and after renal transplantation. Active cytomegalovirus infection developed in 96% of patients after renal transplantation; reactivation of herpes simplex, varicella-zoster, and Epstein-Barr viruses was found in 35%, 24%, and 0% of patients, respectively. Cytomegalovirus viremia developed in 42% of patients an average of two months after renal transplantation, lasted 1.75 (+/- 1.5) months (except in one patient with chronic viremia), and was followed by chronic viruria. Higher titers of infectious cytomegalovirus were found in the polymorphonuclear than in the mononuclear leukocyte fraction. Reactivation of a latent infection and, less likely, respiratory infection appear to be the most probable mechanisms of cytomegalovirus infection after renal transplantation. One to three months after transplant, cytomegalovirus infection may be related to fever, arthralgia, pneumonitis, and leukopenia; three to four months after transplant, the virus may be related to hepatitis; and 12-30 months after transplant, it may be related to retinitis in patients with chronic viremia. Although other causes of these complications are possible, herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, measles virus, adenovirus, hepatitis B virus, and Toxoplasma gondii appear to be of lesser importance than cytomegalovirus in this respect.

Adult↗

Multiple sclerosis-associated agent: transmission to animals and some properties of the agent.

In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease.

Animals↗

Multiple sclerosis-associated agent: neutralization of the agent by human sera.

A total of 172 sera from patients with multiple sclerosis (MS), theri relatives and nursing personnel, patients with other neurological and nonneurological diseases, and healthy donors living in the United State or East Africa under vastly divergent hygienic conditions were examined for their capacity to neutralize the MS-associated agent (MSAA), which induces in experimental animals a transitory depression of circulating polymorphonuclear leukocytes (PMN). A considerable proportion of sera from MS patients and their relatives or nursing personnel and East African donors revealed neutralizing activity, but only one of 59 sera from American donors without known contacts with MS patients revealed neutralizing activity. Some of the sera could be diluted 100- or 1,000- fold and still prevent, or substantially reduce, PMN depressions in mice. The neutralizing activity was shown to be associated with the immunoglobulin fractions of sera and therefore appears to be due to an antibody. Cerebrospinal fluids from MS, but not other, patients also strongly neutralized MSAA. Evidence has been presented that sera from MS patients may contain both MSAA and MSAA neutralizing antibodies. Antigen-antibody complexes were separated from such sera by high-speed centrifugation, and neutralizing antibodies were dissociated from them at a low pH. Whereas the data are as yet limited due to the vagaries and complexities of the test procedures, they provide further evidence that MSAA is not an indigenous virus of experimental animals, causes infections in man, and is indeed closely associated with MS. If it were the cause of MS, which remains to be ascertained, the data imply that not all infections by MSAA lead to the development of MS.

Animals↗