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K Raska

Publications and source records attributed to K Raska.

At least 73 records · Page 4Linked to original sources
PubMed1986

Examination of the low proliferative capacity of human jejunal intraepithelial lymphocytes.

The proliferation of human jejunal intraepithelial lymphocytes (IEL) was examined to determine how it differed from that of peripheral blood (PB) T lymphocytes. The IEL were mainly T lymphocytes of the cytotoxic-suppressor (T8+) phenotype. They demonstrated lower proliferative responses to various stimuli (2,501 +/- 565 ct/min with phytohaemagglutinin; PHA) compared to unseparated PB T lymphocytes (73,678 +/- 2,495) or the T8+ subset (68,939 +/- 10,053 ct/min) (P less than 0.001). This low proliferative response was also a characteristic of the T8+ T lymphocytes in the lamina propria (4,606 +/- 1,226 ct/min) but not the T4+ subset (43,447 +/- 10,188 ct/min) (P less than 0.05). These findings were not due to isolation techniques or to differences in kinetics. Mixing experiments revealed that the IEL did not contain cells which suppressed proliferation. In addition, the IEL could be stimulated by mitogens, as they produced the same amount of interleukin 2 (IL-2) and IL-2 receptors as did PB T lymphocytes. Although the lectin-induced proliferative response of IEL was unaltered by the addition of autologous macrophages and minimally increased by IL-2, it was markedly enhanced by the addition of sheep red blood cells (SRBC). The enhancing effect of SRBC was not due to T cell recognition of xenogenic antigens on the erythrocytes since neither allogeneic non-T lymphocytes nor other xenogenic erythrocytes produced the same effect. Both intact SRBC and membrane fragments from osmotically lysed cells augmented lymphocyte proliferation. Thus, jejunal IEL could be activated by mitogen and proliferated as much as PB T lymphocytes if exposed to a membrane component found on SRBC.

Adult↗
PubMed1986

Effect of danazol on clotting factor levels, bleeding incidence, factor infusion requirements, and immune parameters in hemophilia.

Several recent studies have reported conflicting results on the effectiveness of danazol, an attenuated androgen, in raising plasma levels of clotting factors VIII and IX in patients with hemophilia. We undertook a randomized, double-blind cross-over trial using 8 weeks' administration of danazol (D), 600 mg/d, and 8 weeks' administration of placebo (P) separated by 2 weeks of rest in 12 patients with hemophilia A and four patients with hemophilia B. Plasma factor VIII and IX levels, frequency and type of bleeding episodes, amount of factor concentrate infused, fibrinogen, fibrinolysis assays, antithrombin III, liver function, and immune parameters were followed. During the danazol phase a minimal increase was noted in the average clotting factor levels, an increase that, although statistically significant, was of hemostatically marginal magnitude. Significant increases in protein C and plasminogen levels, however, were observed during the danazol period, suggestive of danazol-mediated enhanced fibrinolysis. Clinically, bleeding frequency was significantly increased, and more clotting factor was consumed during the danazol period. Furthermore, eight episodes of hematuria and oral mucosal bleeding was reported during the danazol phase in contrast to only one episode of hematuria during the placebo phase, consistent with an enhancement of fibrinolytic activity with danazol. We conclude that danazol does not have a hemostatically significant effect on plasma levels of factor VIII and IX but may be associated with enhancement of fibrinolytic activity, resulting in increased bleeding frequency and requiring more clotting factor infusions. Therefore, danazol is not a viable alternative in the treatment of hemophilia.

Blood Coagulation Factors↗
PubMed1985

Tumorigenicity of adenovirus-transformed cells: region E1A of adenovirus 12 confers resistance to natural killer cells.

Sensitivity of a library of rat cells transformed in vitro with viable recombinant adenoviruses to natural killer (NK) cells and allogeneic cytotoxic T cells has been studied and correlated with their oncogenic potential in syngeneic rats. All cell lines transformed with the sub370-12E1AB virus (containing E1A and E1B regions of Ad12) and with the sub370-12E1A virions (containing the E1A region of Ad12 and the E1B region of Ad5) showed a high degree of resistance to NK cells. The cell lines transformed with the sub370-12E1B virus (containing the E1A region of Ad5 and the E1B region of Ad12) were highly sensitive to NK cytotoxicity. While all cell lines transformed with virions containing the E1A genes of Ad5 expressed high levels of class I MHC antigen, only three of eight cell lines containing the E1A region of Ad12 showed detectable levels by flow cytometric analysis after staining with specific antibodies. All cell lines containing E1A genes of Ad5 were killed by in vitro generated allogeneic cytolytic T cells. Only three of eight cell lines containing the E1A region of Ad12 were killed by such CTLs; the level of cytotoxicity, however, did not reach that seen with the cells containing the E1A genes of Ad5. All cell lines containing the E1A and E1B genes of Ad12 were highly tumorigenic. Only two of four cell lines transformed with virus containing the E1A genes of Ad12 and E1B region of Ad5 were tumorigenic. The efficiency of tumor induction was low and the latent period was long confirming the importance of the E1B region. None of the cell lines transformed with virus containing the E1A region of Ad5 and the E1B genes of Ad12 were tumorigenic, reflecting their high degree of sensitivity to both natural and induced cellular immunity. Expression of the E1A region of Ad12 in transformed cells modulates not only the level of class I MHC antigens, but also confers resistance to NK cell cytotoxicity.

Adenoviruses, Human↗
PubMed1984

Tumorigenicity of adenovirus-transformed rat cells and expression of class I major histocompatibility antigen.

The expression of class I major histocompatibility antigens was studied in six syngeneic adenovirus 12 (Ad12)-transformed LIS rat cell lines of varying tumorigenicity. The concentration of MHC class I product was estimated by indirect immunofluorescence staining of viable cells in suspension with specific antibody and cytofluorographic analysis, and by sensitivity to killing by allogeneic cytolytic T cells (CTLs) elicited by immunization with spleen cells in vivo and in mixed lymphocyte reactions in vitro. None of the rat cell lines examined was devoid of MHC class I antigen. When compared to syngeneic Ad2-transformed cells or fibroblasts, the average intensity of fluorescence of Ad12-transformed lines was lower, suggesting that the concentration of MHC class I antigen is somewhat lower in Ad12-transformed cells. Sensitivity to killing by both in vivo and in vitro induced allogeneic CTLs, however, was not markedly lower with Ad12-transformed cells and correlation was not found between tumorigenic potential in vivo and sensitivity to allogeneic T-cell killing in vitro.

Adenoviruses, Human↗
PubMed1984

Acquired immune deficiency syndrome. No evidence of the presence of cyclosporine.

It has been postulated that the acquired immune deficiency syndrome (AIDS) may be a result of the systemic presence of an immunosuppressive cyclosporine-like molecule released in chronic fungal infections. This possibility was examined by analysis of blood, plasma, or serum samples obtained from AIDS patients, from subjects with prodromal AIDS, and from healthy subjects belonging to several of the recognized "AIDS risk groups" for cyclosporine-like substances. The sensitivity of the analytic methods and the stability of cyclosporine during the storage of blood were verified by analysis of blood specimens obtained from a normal volunteer after oral ingestion of various doses of cyclosporine. Radioimmunoassay, high-pressure liquid chromatography, and analysis by combination of these two methods failed to detect cyclosporine or cyclosporine-like substances in subjects with established or prodromal AIDS and in AIDS-free persons belonging to the risk groups. These results indicate that the breakdown of cellular immunity in AIDS is not due to circulating cyclosporine.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Suppressor cells in end-stage renal disease. Functional assays and monoclonal antibody analysis.

Suppressor cell activity after concanavalin A induction was studied in peripheral blood mononuclear cells of patients undergoing long-term hemodialysis. Suppression both of the mixed lymphocyte reaction and of allogeneic cells stimulated with phytohemagglutinin was significantly higher with peripheral blood mononuclear cells from patients undergoing hemodialysis than with cells from control subjects. Expression of the Ia antigen on T lymphocytes (associated with immunologic activation) was studied by staining with monoclonal antibodies and two-color fluorescence analysis in a computer-linked cytofluorograph. In unstimulated cells, there was no significant difference between the patients and control subjects. After concanavalin A induction, the percentage of T4, and particularly of T8, cells expressing the Ia antigen was significantly higher in the group undergoing hemodialysis. The functional suppression seen after concanavalin A induction in the mixed lymphocyte reaction was significantly reduced by treatment with OKT8 monoclonal antibody and complement; in phytohemagglutinin cultures, both OKT8 and OKIa*1 antibodies were effective. The reduced in vitro response of uremic lymphocytes may thus be a consequence of increased suppressor activity associated with the T8-positive, Ia-positive subset of T cells.

Adult↗
PubMed1984

Attachment to and degradation of collagen substrata by adenovirus-transformed cells of varying tumorigenicity.

The interaction of adenovirus-transformed cells of different tumorigenicity with different collagen substrata has been investigated. The adenovirus type 2 (Ad2)-transformed cells are nontumorigenic in syngeneic rats while, the adenovirus type 12 (Ad12)-transformed cells induce tumors with high efficiency. Cells transformed with Ad2 preferentially attach to collagen type I and this attachment is enhanced by fibronectin. Highly tumorigenic Ad12-transformed cells attach less efficiently to collagen type I and their attachment ability is unaffected by fibronectin. These cells, however, strongly attach to type IV collagen and this attachment is considerably enhanced by laminin. Ad2-transformed cells attach less efficiently to collagen type IV and laminin has no effect on this process. The ability of adenovirus-transformed cells to degrade collagen also has been examined. The nontumorigenic cells secrete significant amounts of collagenolytic activity directed against type I collagen into the medium, but very little type IV collagenolytic activity is secreted. The highly tumorigenic cells secrete collagenolytic activity directed against both collagen types I and IV. In addition, their secreted type IV collagenolytic activity is significantly higher than that of the nontumorigenic cells. These results suggest that laminin mediated attachment to and degradation of type IV collagen may play a significant role in determining the tumorigenic and invasive potential of adenovirus-transformed cells.

Adenoviridae↗
PubMed1983

T cell subsets and cellular immunity in end-stage renal disease.

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.

Adolescent↗
PubMed1983

Adenovirus type 12 specific cell surface antigen in transformed cells is a product of the E1b early region.

Six syngeneic rat cell lines transformed with isolated or cloned left end fragments of adenovirus type 12 (Ad12) DNA were used in a study of the Ad12-specific cell surface antigen. Cells transformed with EcoRI-C, SalI-C, and HindIII-G fragments of Ad12 DNA fragment-transformed express the E1a and a part of or a complete E1b early regions. Two AccI-H DNA fragment-transformed cell lines contain and express only the E1a region. All these cells contain nuclear Ad12 antigen. Cytotoxic antibodies raised against syngeneic EcoRI-C DNA fragment-transformed cells kill EcoRI-C, SalI-C and HindIII-G fragment-transformed cells, but fail to kill cells transformed with AccI-H DNA fragment. Immunofluorescence analysis shows that such antibodies, which stain the surface of cells expressing the E1b region, do not stain the surface of AccI-H DNA fragment-transformed cells. Cells transformed with AccI-H fragment are also not killed by secondary cytolytic T cells, raised and effective against cells transformed with EcoRI-C, SalI-C, and HindIII-G DNA fragments. Cells transformed with AccI-H fragment do not elicit cytolytic T cells against any of the studied cell lines. The only Ad12-specific product shared by all cell lines killed in cytolytic assays which is absent from AccI-H fragment-transformed cells is the E1b 18K protein. Since it has also been shown in other studies that this protein is associated with the cellular membrane, the simplest interpretation of these data is that the Ad12-specific cell surface antigen in transformed rat cells is a product of the left end of the E1b region.

Adenoviridae↗
PubMed1983

Humoral inhibitors of the immune response in uremia. V. Induction of suppressor cells in vitro by uremic serum.

The mechanism of inhibition of mixed lymphocyte reaction (MLR) by serum of chronically uremic rats has been studied. The inhibitory activity of the serum has been associated with a discrete subset of very low density lipoproteins (VLDL) of Sf 100-400. The degree of the inhibitory activity of uremic serum correlates with the severity of uremia. Spleen cells from normal rats incubated for 20 hours with uremic serum or its VLDL fraction suppress the response of control syngeneic cells in the MLR. Induction of such suppressor activity does not require cell proliferation because it is not inhibited by mitomycin C. although the exact identity of the induced suppressor cells has not been established, they may be macrophages. The suppressor activity of induced spleen cells can be markedly reduced by filtration of spleen cells on glass wool or on nylon wool columns. Reconstruction experiments show that the adherent cell fraction of spleen cells exposed to uremic serum suppresses the response of the nonadherent fraction of control spleen cells. These results indicate that the immunosuppressive effects of rat uremic serum in vitro involve the induction of suppressor cells.

Animals↗
PubMed1983

Frequency of responsiveness to the H-Y antigen among the B10.W lines.

B10.W females were immunized against syngeneic male cells (via the footpad and also i.p. in some strains) and their spleen cells were then restimulated in vitro and tested in the cell-mediated lympholysis assay for H-Y-specific killing of target cells. Only seven of the 33 tested lines were anti-H-Y responders. The effector cells obtained from each of the responder lines were then tested against male and female cells of other B10.W lines, as well as a number of classic B10 congenic lines, and the MHC molecules providing the context for H-Y recognition were identified. They were: Kk, Kw3, Kw7, Kw17, Kw27, Dk, and Dp. None of the strains generated effector cells capable of recognizing the H-Y antigen simultaneously in the context of the K and D molecules. The WOA1 females generated effector cells by using the Kw7 molecule for context of recognition, whereas the WR7 females produced cells recognizing the H-Y antigen exclusively in the context of the Dk molecule despite the fact that both lines share the Kw7 gene. Some of the effector cells cross-reacted with both male and female cells of other strains and this cross-reactivity could be attributed to the recognition of allogeneic MHC molecules controlled by K or D region genes. Interestingly, STA39 females generated Dp- but not Kw3-restricted anti-H-Y responses, whereas SAA48 females generated Kw3- but not Dw3-restricted responses; the Kw3-restricted cells cross-reacted with the Dp molecule. This cross-reaction might explain why the STA39 females do not mount a Kw3-restricted anti-H-Y response. Because the Kw3 + H-Y combination resembles Dp, the anti-Kw3 + H-Y T cells are functionally eliminated when tolerance of Dp molecules is attained in the STA39 mice.

Alleles↗