Serochemotherapy against a Moloney virus-induced leukemia.
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Biomedical subjects
Publications and source records attributed to G R Pearson.
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Archive central nervous tissue from 286 cats with neurological disorders was reviewed for histological evidence of feline spongiform encephalopathy (FSE), which may have occurred before it was first recognized in 1990. The following six categories of disease were identified: congenital; degenerative; inflammatory; neoplastic; FSE; lesion-free. The largest category (inflammatory) contained 92 cats, of which 47 were considered to be consistent with infection by feline infectious peritonitis (FIP) virus. Six cats showed evidence of more than one disease process; thus, one cat with FIP also had toxocara infection of the lateral ventricles and five cats with FSE also showed perivascular cuffing suggestive of concurrent viral infection. In only two cases did the diagnosis on review differ significantly from the original interpretation. There was no evidence of FSE before the original case was recognized in April 1990.
Four conventionally reared goats aged 6 days were inoculated orally with approximately 10(10) colony-forming units (cfu) of a non-verotoxigenic strain of Escherichia coli O157:H7. All remained clinically normal. Tissues were sampled under terminal anaesthesia at 24 (two animals), 48 and 72 h post-inoculation (hpi). E. coli O157:H7 was cultured from the ileum, caecum, colon and rectum of all animals, but the number of bacteria recovered at these sites varied between animals. Attaching-effacing (AE) lesions associated with O157 organisms, as confirmed by immunolabelling, were observed in the ileum of one of the two animals examined at 24 hpi, and in the ileum, caecum and proximal colon of an animal examined at 72 hpi. E. coli O157 organisms were detected at > or =10(5) cfu/g of tissue at these sites. In addition, AE lesions associated with unidentified bacteria were observed at various sites in the large bowel of the same animals. Lesions containing both E. coli O157 and unidentified bacteria (non-O157) were not observed. Non-O157 AE lesions were also observed in the large bowel of one of two uninoculated control animals. This indicated that three (one control and two inoculated) animals were colonized with an unidentified AE organism before the commencement of the experiment. The O157-associated AE lesions were observed only in animals colonized by non-O157 AE organisms and this raises questions about individual host susceptibility to AE lesions and whether non-O157 AE organisms influence colonization by E. coli O157.
Day old chicks were inoculated with either Salmonella typhimurium or S. Kedougou as representative examples of an invasive and a non-invasive strain respectively. The titres of IgA, IgG and IgM antibodies were determined, using an enzyme-linked immunosorbent assay (ELISA) in the bile, serum and homogenates of intestinal mucosa each week up to 5 weeks of age. Statistically significant increases in antibodies were detected in the bile (IgA and IgG) and the intestinal mucosa and serum (IgG and IgM) 1 week after the birds were inoculated with S. typhimurium. In contrast, only a limited response was recorded for S. kedougou 4 weeks after challenge commenced. The birds appeared capable of eliminating systemic infection with S. typhimurium as they grew older although a cell mediated immune response was demonstrated in less than half the birds aged 4 or 5 weeks. The demonstration of only a limited serological response to S. kedougou indicates that serological testing may have a limited role in monitoring flocks for infection with non-invasive serotypes.
Day-old chicks were inoculated either via the feed or by direct oral inoculation with salmonellas which were either invasive or non-invasive (serotypes Typhimurium and Kedougou, respectively). Colonization of the alimentary tract and visceral organs, determined by microbiological examination, occurred more quickly in birds inoculated orally with S. serotype Typhimurium compared with feed-challenged birds. By contrast, S. serotype Kedougou remained confined to the alimentary tract. In birds inoculated either orally or via the feed, S. serotype Typhimurium, but not serotype Kedougou, was identified in the lamina propria of the caecum by immunostaining. Electron microscopic examination confirmed that the organisms were within macrophages.
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One hundred fifty-one patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective collaborative study of North American patients (most were white). Serum samples were collected concurrently from 903 Mayo patients for comparisons of serologic analyses. Both IgA antiviral capsid antigen [VCA (IgA)] and the anti-early antigen [EA (D)] antibody responses were associated with diagnosis, but not always in the same way. Both responses were positive in 85% of patients with World Health Organization types 2 and 3 NPC. Only 16% with WHO type 1 NPC had positive IgA responses and only 35% had positive EA (D) responses, prevalences close to those in the comparison groups. Increased titers were found in the squamous carcinoma comparison group with tumors of the tongue and in the group with benign nasal polyps (p less than 0.01). We believe that the tests are specific, sensitive, and useful in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.
There is no agreement on the single best staging system for patients with nasopharyngeal carcinoma. We have evaluated prospectively several staging systems and have assessed the predictive value of many variables on survival and found that the most important are extensive tumor within the nasopharynx or regional extension, nodes in the lower portion of the neck, and cranial nerve involvement. Other variables that have not been used in traditional extent of disease staging systems but that have an adverse bearing on survival have been studied by multiple regression techniques in the Cox proportional hazards model. Two prognostic scores, which can be used for classifying patients into survival groups, ranging from excellent survival (low score) to poor survival (high score), have also been presented. With these schemes, patients who are at high risk for recurrence after conventional therapy can be reliably selected.
The Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma, suggesting an etiologic relationship. We have under-taken studies (1) to quantitate the relationship between antibody titers to EBV-associated antigens and nasopharyngeal carcinoma in American patients since most of the patients in previous studies were of either Asian or African descent and (2) to determine the relationship between antibody titers and the clinical course of the disease. Sera from patients with primary or recurrent nasopharyngeal carcinoma and from patients in remission, from patients with various other head and neck tumors (including occult primary lesions and lymphomas), and from normal controls were titrated for IgG antibodies to viral capsid antigen (VCA) and early antigen and IgA antibodies to VCA, using indirect immunofluorescence procedures previously detailed. High titers of antibodies to EBV-induced early antigens and VCA in the IgG fraction and VCA in the IgA fraction were frequently found in the sera of patients with nasopharyngeal carcinoma. A significant reduction in these titers was observed with clinical remission of the disease in treated patients. Preliminary findings suggest that EBV serology may be useful in the evaluation and treatment of patients with nasopharyngeal carcinoma and also in patients with cervical metastases from clinically occult promary sites in order to identify those with occult nasopharyngeal carcinoma.
IgA immunoglobulin fractions containing antibodies to Epstein-Barr virus (EBV)-induced membrane antigens were isolated from the sera of two patients with nasopharyngeal carcinoma (NPC), from one non-NPC patient, and from three persons with sera negative for IgA antibodies. IgA antibodies were not cytotoxic against cells expressing EBV-induced membrane antigens in the antibody-dependent cellular cytotoxicity (ADCC) assay. However, IgA antibodies blocked IgG-mediated ADCC, which indicated that these antibodies could serve as a blocking "factor" in patients with disease and, therefore, were potentially detrimental to the host.
Because antibody titers against Epstein-Barr virus (EBV) antigens often are elevated in patients with active undifferentiated and nonkeratinizing nasopharyngeal carcinoma, anti-EBV serologic tests have been applied as a diagnostic aid in patients who have metastatic lymphadenopathy in the neck without an obvious source. IN this study of 44 patients, the serologic testing procedure proved useful in identifying six patients with nasopharyngeal carcinoma that was initially occult but was eventually confirmed by biopsy.
Two interesting findings have emerged from these studies. First, the NK susceptibility of EBV-related cell lines is dependent upon the state of the virus within the cells. EBV-positive cells were more competitive than their EBV-negative counterparts, and induction of the viral cycle in the EBV-positive cells further increased their ability to inhibit NK reactivity against K562. The implications of this finding with regard to surveillance against, and treatment of, EBV-related disease were discussed. Second, the preliminary data concerning the NK status of patients with head and neck cancer appear interesting, with the patients falling into two relatively distinct clusters of either high or low reactivity. The significane of this clustering will be determined by enlarging the study sample and performing longitudinal NK studies of the patients.
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