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Biomedical subjects

E Kimball

Publications and source records attributed to E Kimball.

7 recordsLinked to original sources

The immunostimulatory compound 7-allyl-8-oxoguanosine (loxoribine) induces a distinct subset of murine cytokines.

C8- and N7, C8-substituted guanine ribonucleosides comprise a class of molecules with potent immunostimulatory activity for a variety of humoral and cellular immune responses. Although it has been suggested that the immunostimulatory activity may be partially mediated by cytokine production, to date there has been no systematic evaluation of the spectrum of cytokines elicited by these nucleosides. In this study, we examine the cytokines produced by murine spleen cells in response to the di-substituted guanosine analog loxoribine (7-allyl-8-oxoguanosine). First, the levels of cytokine mRNA in spleens from vehicle- or loxoribine-treated mice were compared using PCR analysis with a panel of cytokine-specific primers. Enhancement of IL-1 alpha, TNF-alpha, TNF-beta, IL-6, IFN-alpha, and IFN-gamma mRNA was seen in the spleens of loxoribine-treated mice. IL-12 mRNA responses were more complex, with an increase in the p40 chain and a decrease in the p35 chain. In contrast, no increase was seen for mRNA levels of IL-2, IL-3, IL-4, IL-5, IL-7, or GM-CSF. ELISA assays on the supernatants of loxoribine-treated spleen cells demonstrated that IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were all produced in a dose-dependent fashion with TNF-alpha produced first, followed by IL-6 and IFN-gamma, and last by IL-1 alpha. IFN-alpha beta activity rose as quickly as TNF-alpha, leveling off at 8 to 12 hr, and was supplanted by a later-occurring surge of IFN-gamma production. IL-1 alpha, IL-6, TNF-alpha, and IFN-gamma were also detected in the sera of mice injected with loxoribine. When antibodies against the relevant cytokines were tested, only anti-IFN-alpha beta inhibited NK activity or lymphocyte proliferation and, in both cases, activity was partially restored by the addition of exogenous IFN-alpha beta. Taken together, these data indicate that loxoribine induces the production of a selective cohort of cytokines all of which have been shown to have immunostimulatory activity. However, only IFN-alpha beta appears to play a role in the enhancement of NK activity and lymphocyte proliferation.

Animals↗

Eosinophilia in Southeast Asian refugees: evaluation at a referral center.

We determined the cause of persistent eosinophilia in 128 Indochinese refugees for whom initial comprehensive routine screening had failed to yield an explanation. Intestinal parasitism with one or multiple organisms was the cause of eosinophilia in all but six of these patients. Hookworm and Strongyloides stercoralis were among the potentially pathogenic organisms most frequently implicated (55% and 38%, respectively). There was no correlation between the age or sex of the patients and the type of infecting organism. We also confirmed the usefulness of a previously described serological test for diagnosing infection with Strongyloides stercoralis and examined the test's ability to distinguish between infected and noninfected individuals and to determine parasitological cure.

Adult↗

Two new monoclonal antibodies to human monocytes and granulocytes: isolation of membrane antigens and lack of effects of antibodies on leukocyte functions in vitro.

Mice were immunized with purified human monocytes or granulocytes obtained by leukapheresis and isolated on dextran gradients or by countercurrent centrifugation-elutriation. A monoclonal antibody, Mo95, was generated in response to monocytes and was found to react strongly with monocytes, large granular lymphocytes (LGL), granulocytes, eosinophils, and some myelomonocytic leukemia cells, but not with normal T or B lymphocytes, platelets, red cells, or leukemic cell lines. Mo95 is an IgG1 antibody, which precipitated a 95 kD molecular weight antigen. Addition of the Mo95 antibody to monocytes in the absence of complement did not inhibit lysozyme secretion nor did it affect superoxide production, C3b-rosetting, nitrotetrazolium blue reduction, phagocytosis, or chemotactic responses. A second antibody, PMN70, was found to react exclusively with granulocytes and not with monocytes, lymphocytes, LGL, platelets, red cells, or any of the myelomonocytic, T-cell-derived or B-cell-derived leukemic cell lines tested. The PMN70 antibody immunoprecipitated a 70 kD molecular weight antigen found only on mature granulocytes. Mo95 and PMN70 appear to be distinct from five other tested monoclonal antibodies reactive to monocytes and/or granulocytes on the basis of the fluorescent cell sorter and immunoprecipitation studies performed.

Animals↗

Monoclonal antibody therapy of malignant melanoma: in vivo localization in cutaneous metastasis after intravenous administration.

The murine antimelanoma monoclonal antibody, 9.2.27, was administered intravenously to eight patients with metastatic malignant melanoma. Biopsies of metastatic nodules clearly demonstrate the selective localization of this antibody on the melanoma cell surface with a dose-response relationship to the quantity of administered antibody. The antibody infusions were clinically well tolerated and the pharmacokinetics of the antibody and the antiglobulin responses are described. This study indicates that murine monoclonal antibodies have potential as selective targeting agents in the design of future therapeutic trials using monoclonal antibodies or conjugates thereof in the treatment of cancer.

Adult↗

Correctness of racial coding of American Indians and Alaska Natives on the Washington State death certificate.

Underestimation of death rates for specific races can obscure health problems and impair the ability of public programs to prevent premature death and disability. For accurate race-specific death rates, the racial classification of both the population at risk and the decreased population must be accurately ascertained. However, studies suggest that the American Indian (AI) and Alaska Native (AN) races may be not be accurately recorded on the death certificate. We performed a computerized linkage between the Indian Health Service (IHS) patient registry and the 1985-1990 computerized Washington State death certificate data. The deceased was correctly identified as AI or AN on the death certificate for 1,088 (87.2%) of 1,248 matched deaths. The majority (93%) of deceased persons identified on the death certificate as not AI or AN were listed as white. The percentage of American Indian ancestry was strongly associated with correct racial classification on the death certificate (P < .001). Birth in Washington State, membership in a large Washington State tribe, and death from an alcohol condition independently added to the likelihood of correct AI or AN racial classification. Persons who died from cancer were significantly less likely to be correctly coded as AI or AN on the death certificate.

Alaska↗