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Biomedical subjects

J M Easton

Publications and source records attributed to J M Easton.

At least 19 recordsLinked to original sources

Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat.

Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked pain behaviors. We hypothesized that QUIS-induced inflammation and subsequent gene expression contribute to the development and progression of pain-related behaviors and that blockade of inflammation-related gene expression leads to the amelioration of these behaviors. Using the QUIS model of spinal cord injury, we examined whether interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is able to reduce mRNA levels of inflammatory and cell death-related genes leading to a reduction of pain behaviors. The results demonstrate that animals receiving systemic injection of IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), CD95 ligand (CD95-L, also called FAS-L/APO-1L), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results of QUIS injury plus IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS mRNA and these results were supported by Western blot analysis of protein levels following IL-10 treatment. These data suggest that IL-10 reduces inflammation and that targeting injury-induced inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors.

Animals↗

The American Burkitt's Lymphoma Registry: eight years' experience.

Four-hundred-twenty-one Americans diagnosed as having Burkitt's lymphoma (BL), 409 from the United States, were studied by the American BL Registry to obtain information about the cause and control of this disease. Of these 421 cases, 256 were confirmed by our pathologists as being morphologically indistinguishable from African BL, A relationship between age and organ involvement was observed; cervical lymph nodes, ileum, and nasopharynx were initial sites of involvement primarily in younger patients. Although the Epstein-Barr virus (EBV) was less frequently associated with American BL than African, a high antibody titer to the EBV capsid antigen was associated with a more favorable prognosis. American BL resembled African BLs time-space clustering, male predominance, and excellent response to chemotherapy. Unlike African BL, however, more patients had involvement of cervical lymph nodes and bone marrow at an early stage of disease. American BL appears to be a more heterogeneous disease than African BL.

Adolescent↗

Demographic patterns for nasopharyngeal carcinoma in the United States.

Demographic and pathologic information on over 1,000 newly diagnosed patients with nasopharyngeal carcinoma was obtained from population-based registries in the United States. Age-adjusted incidence rates were similar for whites and blacks and both were significantly lower than for Chinese Americans. Age-related differences in cell type were observed in white NPC patients, lymphoepithelial carcinomas having a younger age distribution than either squamous-cell or transitional-cell carcinomas. Mortality rates for nasopharyngeal cancer were substantially lower than incidence rates for nasopharyngeal carcinoma, but both indices revealed a minor peak in rates among teenaged whites and blacks. The five-year survival rate for nasopharyngeal carcinoma was less than 25% and has not changed in recent years. Prognosis was better for females and for young patients. Despite the difficulties in obtaining uniform pathologic classification in such a large study, the interrelationship between pathologic subtype of nasopharyngeal carcinoma and demographic features emphasizes the need for adherence to a more uniform histologic classification.

Adolescent↗

Nasopharyngeal carcinoma in the United States. A pathologic study of 177 US and 30 foreign cases.

Making use of a new histologic classification developed by the World Health Organization, we reviewed 177 US and 30 foreign cases of nasopharyngeal carcinoma (NPC). Tumors of US whites included undifferentiated, squamous cell, and non-keratinizing carcinomas, while US blacks had undifferentiated carcinomas only. There were no significant histological differences between the tumors from US- and foreign-born patients. White male subjects from the United States had a braod age distribution, with a peak in the 60- to 69-year range. Black subjects from the United States, on the other hand, had a prominent incidence peak in the 10- to 19-year age range. These pathologic and age-related differences may provide clues as to those factors involved in the cause and pathogenesis of NPC.

Adolescent↗

Extraction of soluble antigens of Epstein-Barr virus, Herpesvirus salmirl, and Herpesvirus ateles with the use of glycine.

For extraction of soluble antigen from cells infected with Epstein-Barr virus, Herpesvirus salmirl, and H. ateles, 0.1 M glycine (pH 9.5) was used. This method yielded increased amounts of the antigen containing much less cell debris. Lymphoblastoid cells infected with Epstein-Barr virus could maintain up to 50% viability after the extraction procedure. These cells could be used again after an appropriate interval in culture. The usefulness of this technique is discussed.

Antigens, Viral↗

Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines.

We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.

Animals↗

Herpesviruses and cancer in man and subhuman primates.

Because there is strong evidence for the involvement of Epstein-Barr virus in the etiology of Burkitt's lymphoma and nasopharyngeal carcinoma, we have discussed the relationship of Epstein-Barr virus to these two diseases in the context of geographic distribution, pathology, epidemiology, genetics, immunovirology, and biochemistry. We have also discussed the relationship of Epstein-Barr virus to other diseases, both malignant and non-malignant. Although the etiologic relationship of herpes simplex virus type 2 to squamous carcinoma of the uterine cervix is not on as firm ground, we feel that some good evidence does exist. We have also discussed two oncogenic simian viruses, Herpesvirus saimiri and Herpesvirus ateles. These have a great number of similarities to EBV, and thus may provide models for the study of viral-induced oncogenesis in man. Agents similar to Epstein-Barr virus have been isolated from old world monkeys. These may possibly be of greater importance than either Herpesvirus saimiri or Herpesvirus ateles in the investigation of human virally-induced cancers.

Animals↗

Absence of horizontal transmission of herpesvirus saimiri between experimentally infected and noninfected owl monkeys.

We did not detect cell-free Herpesviurs saimiri (HVS) in the oropharyngeal secretions of owl monkeys with leukemia or lymphoma induced by this virus. These animals failed to transmit either virus or disease to their uninoculated cage-mates or room-mates. Comparison of oropharyngeal secretions of HVS from owl monkeys and squirrel monkeys may provide insight as to how human herpesviruses are maintained in the oropharynx.

Animals↗

Preventive vaccination against Herpesvirus saimiri-induced neoplasia.

In this paper we discuss the use of Herpesvirus saimiri as a model for the development of vaccines against herpesvirus-induced neoplasia in primates. Attempts at protection against the oncogenicity of H. saimiri have centered on the inactivation of virus by heat and formalin, the production of temperature-sensitive H. saimiri mutants, and the attenuation of the virus. Each of these approaches has provided information of use in the development of vaccines that may possibly be used in man.

Animals↗

Murine cytomegalovirus: induction of and sensitivity to interferon in vitro.

Moderate amounts of viral inhibitor were produced by mouse embryo (ME) cultures infected with two strains of plaque-purified murine cytomegalovirus (MCV). This inhibitor was shown to be interferon, based on the possession of similar properties. The growth studies of MCV in ME cells showed that interferon was produced as early as 4 h after infection, infectious virus was produced between 12 to 16 h, and cytopathic effect was produced between 16 to 18 h. Since MCV-induced interferon production and the subsequent development of antiviral state occurred early, the long eclipse period may be due to an interferon-mediated delay of virus replication. Pretreatment of ME cells with varying concentrations of interferon before infection with MCV did not result in increased interferon production, but at high pretreatment doses a slight inhibitory effect on interferon production was observed. In vitro sensitivity studies showed that small doses of MCV were highly sensitive to the antiviral action of interferon, but higher viral doses proved to be markedly resistant. Although the available evidence does not permit a definitive interpretation of the mechanism by which MCV may show differing sensitivities to interferon action, the presence of a small interferon-resistant fraction of virus-infected cells may account for the observations.

Animals↗

Some biological properties of herpesvirus saimiri from chronically infected monolayer and suspension cultures.

HVS-MEST cells, which are adherent, produced more infectious HVS at 37 degress C than at 33 degrees C. This was paralleled by the appearance of EA and LA in rounded cells and CF antigen in the cell cultures. In contrast, MLC-1 cells, which grow in suspension, produced hardly any infectious virus, but did produce more HVS S antigen than did the HVS-MEST cells. Production of S antigen in MLC-1 cells was augmented by treatment of the cells with BUDR. HVS-MEST cells could be superinfected with HVS, but MLC-1 cells were resistant to super-infection. The unpurified S antigens from both cell lines gave almost identical spectra when tested in CF against a battery of 10 owl and squirrel monkey sera. Thus, two cell lines have been described, one that produces infectious virus and S antigen, and another that produces more S antigen, but in the absence of any great amounts of infectious virus.

Antibodies, Viral↗