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Biomedical subjects

G R Pearson

Publications and source records attributed to G R Pearson.

At least 109 records · Page 6Linked to original sources
PubMed1984

Antibody-dependent cellular cytotoxicity and disease course in North American patients with nasopharyngeal carcinoma: a prospective study.

It has previously been reported that antibody-dependent cellular cytotoxicity (ADCC) levels determined at diagnosis against Epstein-Barr virus (EBV)-specific membrane antigens (MA) are predictive of disease course following therapy in patients with nasopharyngeal carcinoma (NPC). In general, survival was significantly shorter following therapy in patients with low ADCC titers at diagnosis versus those with high titers. To examine this further, a prospective study on North Americans with different histopathological types of this disease was initiated approximately 5 years ago. The results to date tend to support the conclusions drawn from the retrospective study for patients with the more poorly differentiated types (WHO 2 and WHO 3) of this disease. Over the first 3 years of this study, approximately 75% of the patients in the "high" category have remained clinically disease-free for 3 years or longer as opposed to approximately 35% of the patients in the "low" group. Disease progression rates were calculated to be approximately four times higher in the low group. Similar trends were noted in actual survival rates over a 3-year period. ADCC titers were in general found to be relatively stable in sequential serum samples from the same patient, with some exceptions. With the exceptions, however, changes in ADCC titers also reflected disease course. These results indicate, therefore, that anti-EBV ADCC titers are predictive of disease course in patients with the poorly differentiated types of NPC.

Actuarial Analysis↗
PubMed1984

A sensitive enzyme-linked immunosorbent assay (ELISA) against the major EBV-associated antigens. I. Correlation between ELISA and immunofluorescence titers using purified antigens.

An enzyme-linked immunosorbent assay (ELISA) was developed for the major Epstein-Barr virus (EBV) associated antigens. The ELISA assay was based on purified protein components of virus-capsid antigen (VCA), early antigen (EA), membrane antigen (MA) and the nuclear antigen (EBNA). These antigens, except EBNA, were purified on immunoaffinity columns containing monoclonal antibodies, while EBNA was purified by biochemical methods. Screening of 69 human sera including 26 sera from individuals with infectious mononucleosis against these antigens in ELISA showed a good correlation with immunofluorescence titers against the major groups of EBV associated antigens. The results indicated that the ELISA technique using purified EBV proteins could be useful for detecting and monitoring antibody responses to different EBV proteins in patients with EBV-associated diseases.

Antigens, Viral↗
PubMed1984

Antibody-dependent cellular cytotoxicity. Relation to stage and disease course in North American patients with nasopharyngeal carcinoma.

A prospective study of North American patients, mostly white, with different histopathologic types of nasopharyngeal carcinoma was initiated approximately five years ago. Several anti-Epstein-Barr virus (EBV) serologic tests are being evaluated; one is the antibody-dependent cellular cytotoxicity (ADCC) assay, which measures antibodies to an EBV-induced membrane antigen component. A low ADCC titer at diagnosis reflects a poor prognosis, and the determination of antibody titers by this assay identifies patients in whom recurrent disease is likely to develop after conventional radiation therapy for World Health Organization types 2 and 3 carcinomas. Of the patients who had high ADCC titers at diagnosis, 80% survived three years or longer, whereas 50% of the patients with low titers survived three years, and only 35% survived five years. High and low ADCC titers were seen in all stages (except in Ho stage V), and the distribution of patients by high and low ADCC titers was similar in each of the stage groupings. We conclude that the ADCC titer at the time of diagnosis is generally predictive of the prognosis. Clinical staging is the traditional approach for predicting prognosis, but determination of the ADCC titer can be used to segregate patients within the stage groups into those with "good" and "poor" prognoses. Serologic testing may eventually become one of the methods for staging patients with WHO types 2 and 3 nasopharyngeal carcinoma.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Production of monoclonal antibody to a late intracellular Epstein-Barr virus-induced antigen.

A monoclonal antibody designated L2 was produced against a late intracellular protein induced by Epstein-Barr virus (EBV). This protein was expressed in cells producing virus but not in EBV genome-positive nonproducer cell lines, EBV genome-negative cell lines, or producer cultures cultivated in the presence of phosphonoacetic acid as determined by immunofluorescence. In addition, the antibody did not react with the membranes of infected cells indicating that it was not directed against an EBV-induced membrane antigen component. The monoclonal antibody was shown to recognize a glycoprotein with a molecular weight of approximately 125K by SDS-polyacrylamide gel electrophoresis. This glycoprotein was consistently found to be slightly larger when isolated from the P3HR-1 cell line as opposed to the B-95-8 cell line. A similar difference was also noted by comparison of peptide maps of this protein isolated by immunoaffinity chromatography from the two cell lines. Serological studies indicated that this 125K glycoprotein was a major component of the viral capsid-antigen (VCA) complex as defined by immunofluorescence.

Antibodies, Monoclonal↗
PubMed1984

Rapid detection of cytomegalovirus in MRC-5 cells inoculated with urine specimens by using low-speed centrifugation and monoclonal antibody to an early antigen.

A commercially available monoclonal antibody directed against an early nuclear protein of cytomegalovirus was used with low-speed centrifugation for the rapid detection of this virus from urine specimens inoculated onto MRC-5 cells. A total of 19 of 162 (11.7%) urine specimens inoculated were positive by both immunofluorescence and peroxidase-antiperoxidase procedures (sensitivity, 100%), whereas only 18 of the samples produced cytopathic effects in conventional cell culture (specificity, 94.7%). All specimens were positive by immunofluorescence and peroxidase-antiperoxidase procedures at 36 h postinfection, whereas an average of 9 days was required for cytopathic effects to develop in cell cultures.

Adolescent↗
PubMed1984

Identification and characterization of a cellular protein that cross-reacts with the Epstein-Barr virus nuclear antigen.

A 62,000-dalton (62K) cell protein reacts with antisera to the 72K polypeptide of the Epstein-Barr virus nuclear antigen (EBNA) in immunoblots. This protein was initially detected in EBNA-negative as well as EBNA-positive cell lines with anti-EBNA-positive human sera. A monoclonal antibody raised against the 72K EBNA and an antiserum from a rabbit immunized with the glycine-alanine domain of EBNA also reacted with the cellular protein. The cellular protein was partially purified from Epstein-Barr virus genome-positive and -negative cell lines. Absorption experiments identified a shared antigenic determinant between the 72K EBNA and 62K cellular protein. A comparison of the 62K protein and EBNA by protease digestion did not reveal similar peptides.

Antibodies, Monoclonal↗
PubMed1984

Characterization of Epstein-Barr virus nuclear antigen(s) in different cell lines by radioimmunoelectrophoresis.

Utilizing radioimmunoelectrophoresis, Epstein-Barr virus nuclear antigens (EBNA) with molecular weights of 67,000 and 70,000 were detected in NC37 cells, while the Raji cell line contained an antigen with a molecular weight of 70,000. Cell lines containing the B-95 strain of Epstein-Barr virus (EBV) expressed antigens with a molecular weight of 73,000. Three different B-lymphocyte cell lines, established by infection with the B-95 virus, also exhibited 73,000 molecular weight EBNA proteins. Cell lines containing the P3HR-1 strain of EBV demonstrated a single antigen with a molecular weight of 72,000. The results indicate that the molecular weight of EBNA is determined by the strain of infecting virus.

Antigens, Viral↗
PubMed1983

Partial purification of the Epstein-Barr virus nuclear antigen(s).

The Epstein-Barr virus nuclear antigen (EBNA) is speculated to be involved in cell transformation by the virus. Studies on the molecular properties of EBNA, however, have yielded conflicting results. In this study, three Epstein-Barr virus(EBV)-induced antigens were isolated and purified from extracts prepared from Raji cells. These antigens were able to block the anticomplement immunofluorescence reaction, indicating that all three were related to EBNA. The soluble antigen was found wholly in the cytosol fraction. An EBV-induced nuclear antigen I was found both in the cytosol and the nucleus. The EBV-induced nuclear antigen II was found associated with the chromatin. The soluble antigen and the nuclear antigen I were separated and partially purified using phosphocellulose chromatography. Each was further purified 1,400-fold with respect to the whole cell state by chromatography on CL-Sepharose 6B followed by blue dextran-Sepharose. subunit molecular weights of 70,000 were determined for each of these antigens, both in the crude and purified state, by radioimmunoelectrophoresis and gel filtration. The nuclear antigen II was purified 2,500-fold using hydroxylapatite, CL-Sepharose 6B, and blue dextran-Sepharose chromatographies. This antigen displayed two subunits by radioimmunoelectrophoresis with molecular weights of 65,000 and 70,000. Although all antigens shared similar molecular weights, the extent of their homology remains to be determined.

Antigens, Viral↗
PubMed1983

Application of Epstein-Barr virus (EBV) serology to the diagnosis of North American nasopharyngeal carcinoma.

A cooperative study was established among a number of institutions in the USA to determine the clinical value of Epstein-Barr virus (EBV) serology for the diagnosis of different histopathological types of North American nasopharyngeal carcinoma (NPC) including occult primary tumors. One hundred-twenty-four patients with confirmed NPC have now been entered into the study. For each patient, anti-EBV antibody titers were determined at diagnosis and related to the histopathology as classified according to the World Health Organization (WHO). The results suggest that certain anti-EBV antibodies are of potential value for the diagnosis of undifferentiated types of NPC but not for the well-differentiated cancer. The IgA anti-VCA antibody response is the most specific for this disease and of the greatest diagnostic value when used alone or in combination with the anti-EA test. These tests have also been used successfully for the detection of occult NPC. These results indicate that these tests can be useful aids to the clinician for the diagnosis of certain histopathologic types of this disease.

Antigens, Viral↗
PubMed1983

Identification of polypeptide components of the Epstein-Barr virus early antigen complex with monoclonal antibodies.

Three monoclonal antibodies were produced against the Epstein-Barr virus-induced early antigen complex. These antibodies were shown to be specific for the early antigen complex by the fact that they only reacted with cells supporting a permissive or abortive Epstein-Barr virus infection and their synthesis was not affected by inhibitors of viral DNA synthesis. One monoclonal antibody, designated R3, was directed against a diffuse component of the early antigen complex since it reacted by immunofluorescence with cells fixed in acetone or methanol. The other two monoclonal antibodies, designated K8 and K9, reacted with a methanol-sensitive restricted component of this complex. The appearance of the R3 antigen in P3HR-1 superinfected Raji cells occurred approximately 4 h earlier than the antigen detected by K8. By both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radioimmunoelectrophoresis, it was determined that the R3 monoclonal antibody recognized two major polypeptides with molecular weights of approximately 50,000 to 52,000, whereas K8 and K9 precipitated a protein of approximately 85,000. The R3 monoclonal antibody also immunoprecipitated an in vitro primary translation product. It was, therefore, possible to map this product to the Epstein-Barr virus DNA BamH1 M fragment. These in vitro products were slightly smaller than the in vivo proteins, suggesting that these proteins probably undergo posttranslational modification during the virus replication cycle.

Animals↗
PubMed1983

Application of Epstein-Barr virus serology to the diagnosis and staging of North American patients with nasopharyngeal carcinoma.

From 1978 to 1981, 151 patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective, collaborative study of North American patients, most of them white. Thirty-seven had World Health Organization (WHO) type 1 tumors, and 114 had WHO types 2 and 3 tumors. The anti-Epstein-Barr virus (EBV) profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in 85% of the patients with WHO types 2 and 3 tumors but in only 16% of the patients with WHO type 1 tumors. Geometric mean titers tended to be higher in higher stages of the disease in several staging systems. Low antibody-dependent cellular cytotoxicity at diagnosis appears to reflect a poorer prognosis, and the determination of antibody titers by this assay may prove to be useful for identifying persons in whom recurrent disease is likely to develop after conventional therapy. Anti-EBV titers can aid in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.

Adolescent↗
PubMed1983

Natural killer cells in relation to Herpesvirus saimiri-induced disease course and manifestations in owl monkeys.

Infection of owl monkeys with Herpesvirus saimiri (HVS) results in disease courses ranging from chronic infections to fatal cancers. Malignant disease manifestations include the appearance of transformed T-cells, suppressor T-cells, and virus-carrying cells in the peripheral circulation. The reasons for the variability in disease course remain unknown. This study examined natural killer (NK) functions in relation to disease manifestations following HVS infection. The results from lymphocyte fractionation studies indicated that the owl monkey NK cell was of T-cell lineage and had receptors for the Fc fragment of IgG. Following virus infection, NK activity was enhanced in parallel with the appearance of transformed and suppressor cells in monkeys that developed malignant disease. Further studies on the relationship of these three disease characteristics indicated that they involved at least partially different T-cell subpopulations. The results further indicated that the different disease manifestations induced by HVS were polyclonal and at least partially independent events.

Animals↗
PubMed1983

The pathology of neonatal enteritis in calves with observations on E. coli, rotavirus and Cryptosporidium.

The mucosa of the small intestine of neonatal calves responds in a similar way to a variety of infectious agents. However, samples should be removed under general anaesthesia to avoid post-mortem artefacts. These include the separation of epithelium from the villous lamina propria and denudation of villous tips within a few minutes of death, and occur more rapidly in challenged animals. Pathological changes consist of blunting and fusion of the villi with a reduction of the columnar epithelium to cuboidal and occasionally squamous epithelium. A surface inflammatory exudate may be present, especially within 24 hours of challenge with enteropathogenic E. coli. Examination of several sites from the small intestine indicates a variable distribution for enteropathogens. Rotavirus is seen by immunofluorescence microscopy in epithelial cells principally in the proximal half of the small intestine, although they may occasionally be found in the distal half. By contrast, E. coli organisms adhere to enterocytes in the distal half of the small intestine. Cryptosporidia inhabit the brush border of the enterocytes enclosed within host cell microvillous membranes, principally in the distal half of the small intestine. Examination of the small intestine of neonatal calves for pathological changes and the presence and distribution of infectious agents complements bacteriological, virological and immunological techniques in the diagnosis of neonatal enteritis.

Animals↗
PubMed1983

Scanning and transmission electron microscopic observations on the host-parasite relationship in intestinal cryptosporidiosis of neonatal calves.

The association of cryptosporidia with the intestinal epithelium of three neonatal calves was studied by scanning (SEM) and transmission (TEM) electron microscopy. Trophozoites and schizonts were observed embedded in the microvillous brush border of epithelial cells. Merozoites, released from schizonts, were seen free in the lumen and penetrating epithelial cells by SEM and TEM. Incorporation of microvilli into the parasitophorous envelope of trophozoites was seen by TEM. These findings indicate that cryptosporidia develop at an intracellular position in the apex of the epithelial cells following merozoite penetration.

Animals↗