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Biomedical subjects

K Raska

Publications and source records attributed to K Raska.

At least 37 records · Page 2Linked to original sources
PubMed1991

Mixed lymphocyte reaction-induced release of soluble IL-2 receptor.

We studied the release of soluble interleukin 2 receptor (sIL-2R) by PBMC in mixed lymphocyte reaction (MLR) in order to clarify the significance of high plasma levels of sIL-2R in transplant patients undergoing rejection. Levels of sIL-2R were shown to increase progressively after the first day of the MLR and reached their peak on day 5. This pattern of sIL-2R correlated with the incorporation of [3H]thymidine. CsA and prednisolone (PRED) were added at the beginning of the MLR and were shown to inhibit the release of sIL-2R. This inhibition correlated with an inhibition of the [3H]thymidine incorporation. When CsA and PRED were added 24 hr after the initiation of the MLR, a similar inhibition of sIL-2R release was observed, but when they were added 48 hr after the initiation or in the last day of the MLR little or no effect was observed. Incubation of responder or stimulator-responder cells with either CsA or PRED before the initiation of MLR showed that only CsA preincubation was accompanied by decreased [3H]thymidine incorporation. Preincubation with CsA inhibited the release of sIL-2R, whereas PRED had a variable effect. Recombinant IL-2 was shown to augment the release of sIL-2R even at very low doses, but it did not alter significantly MLR-induced [3H]thymidine incorporation. The addition of rIL-2 at the initiation of the MLR was also shown to reverse completely the PRED inhibition of the MLR-induced release of sIL-2R and of the [3H]thymidine incorporation. Addition of rIL-2 reversed only partially CsA-induced inhibition. Addition of different concentrations of sIL-2R at the initiation of the MLR were not shown to affect incorporation of [3H]thymidine. We conclude that the release of sIL-2R in response to alloantigens is an IL-2-dependent phenomenon, and determination of its levels might be a useful indicator of either in vitro or in vivo alloantigen responses and of the effectiveness of immunosuppressive treatment.

Cells, Cultured↗
PubMed1991

Human adenovirus type 9-induced rat mammary tumors.

Following subcutaneous inoculation of newborn Wistar-Furth rats with human adenovirus type 9 (Ad9), 16 of 16 female and 0 of 11 male rats developed mammary tumors. Tumor-positive animals usually developed tumors in multiple glands. Histopathological analyses indicated that three general categories of tumor could be identified. Mammary fibroadenomas were the most common tumor type encountered, but phyllodeslike tumors and solid sarcomas were also frequently found. In situ hybridization and immunohistochemical techniques established that benign fibroadenomas were derived from mammary fibroblasts (collagen type I- and vimentin-positive cells) and that malignant tumors were derived from myoepithelial cells (collagen type IV-, vimentin-, and muscle-specific actin-positive cells). The fact that mammary tumors were limited to female rats suggested that female hormones are essential for tumor growth and development. In this regard, ovariectomy of Ad9-infected female rats prevented tumor development, while subsequent diethylstilbestrol (DES) treatment elicited tumor formation. In addition, Ad9-infected and castrated male rats which received DES also developed mammary tumors. Established male mammary tumors regressed when DES treatment was stopped and reappeared after DES treatment was resumed. Together, these results indicate that estrogen is required for both initiation and maintenance of Ad9-induced mammary tumors. Southern blot analysis of high-molecular-weight tumor DNA showed that mammary tumor cells contained single or multiple integrated copies of the entire Ad9 genome. RNase protection experiments established that estrogen receptor as well as Ad9 E1a and E4 mRNAs were expressed in mammary tumors, but Ad9 E3 and, surprisingly, E1b mRNAs were not expressed at detectable levels.

Adenoviruses, Human↗
PubMed1991

Production and kinetics of interleukin-1 in hemodialysis. In vivo and in vitro study.

Interleukin-1-beta (IL-1-beta) was measured in the plasma and peripheral blood mononuclear cell lysates of uremic patients undergoing maintenance hemodialysis by means of either cuprophane or polysulfone membranes. Basal plasma levels of IL-1-beta in hemodialyzed patients were strikingly higher than those of uremic patients on conservative treatment or of healthy subjects. Plasma levels of IL-1-beta in uremic patients increased significantly after 3 and 6 months of hemodialysis. The study of the kinetics of IL-1-beta concentration during a single hemodialysis session revealed that the concentration of IL-1-beta fell to 21 and 22% of the predialysis level with cuprophane and polysulfone, respectively. Hemodialysis patients also had a significantly higher intracellular IL-1-beta level than normal controls. During the hemodialysis session, an increase in cell-associated IL-1-beta was seen regardless of the membrane employed. In a parallel study, normal mononuclear cells were subjected to closed-loop in vitro dialysis with either cuprophane or polysulfone membranes, with or without acetate buffer. After 120 min of recirculation, an increase in cell-associated IL-1-beta was detected, but no changes were seen in the circulating medium. IL-1-beta production was not significantly influenced by either membrane or the dialysate composition. Hemodialysis has been associated with high plasma- and cell-associated IL-1 levels. The kinetics of intradialytic changes of IL-1-beta levels make IL-1 an unlikely cause of acute complications in hemodialysis. On the other hand, a chronic elevation of IL-1 in plasma of patients on maintenance hemodialysis may contribute to the development of some of the long-term complications of this treatment.

Biocompatible Materials↗
PubMed1991

Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release.

We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.

Aged↗
PubMed1990

Alpha-interferon structure and natural killer cell stimulatory activity.

Expression vectors for human alpha-interferon (Hu-IFN-alpha) J1, a site-specific mutant [Ser116]Hu-IFN-alpha J1, and Hu-IFN-alpha J/C or Hu-IFN-alpha C/J hybrids were constructed and expressed in Escherichia coli. These interferons and others were purified by immunoaffinity chromatography with a monoclonal antibody against human alpha-interferon. Their antiviral activity and ability to stimulate natural killer cell activity were determined in comparison to several other human interferons. These results provide some insight into structure-activity relationships for stimulating natural killer cells and confirm our previous conclusions that antiviral activity cannot be used to predict other activities for an individual IFN-alpha species. The observations suggest that the tertiary structure rather than any specific linear sequence of amino acids regulates the ability of the interferons to stimulate natural killer cell activity.

Amino Acid Sequence↗
PubMed1990

Soluble interleukin-2 receptors in patients with systemic sclerosis. Clinical and laboratory correlations.

Plasma levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean +/- SEM 866.0 +/- 63.6 units/ml versus 293.0 +/- 20.5; P less than 0.001). Soluble IL-2R levels were highest in patients with generalized disease, were strongly associated with mortality (P less than 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL-2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL-2R release. Circulating IL-2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement of sIL-2R may prove to be a useful laboratory technique for assessing disease activity.

Adult↗
PubMed1990

Soluble and cellular markers of immune activation in patients with systemic sclerosis.

The peripheral blood lymphocyte pattern, the lymphocyte responses in vitro, as well as the soluble markers of immune activation were studied in 24 patients with systemic sclerosis (SSc patients). The proportions of total T cells (CD3), their CD4 subset, as well as B lymphocytes were within the normal range. The relative proportion of CD8 lymphocytes, however, was significantly reduced. Patients with SSc had a slightly lower percentage of CD4/4B4+ cells, whereas their proportion of CD4/2H4+ cells was elevated as compared to healthy controls. The proportion of lymphocytes expressing the interleukin-2 receptor (IL-2R) was significantly higher in SSc patients. The proliferative responses of peripheral blood mononuclear cells to PHA stimulation were reduced in the patient group, while expression of IL-2R on lymphocytes after such in vitro stimulation was comparable to that of controls. Expression of IL-2R on patient but not control lymphocytes was increased after in vitro exposure to laminin. Such exposure failed to induce IL-2 production or cell proliferative responses. Soluble plasma IL-2R level (sIL-2R) and soluble CD8 (sCD8) molecule levels in SSc patients were significantly elevated. These results indicate the presence of an ongoing lymphocyte activation in this disease process.

Adult↗
PubMed1990

Impact of perceived self-efficacy in coping with stressors on components of the immune system.

This experiment examined the impact of experimentally varied perceived self-efficacy in exercising control over stressors on components of the immunological system. Immunological changes while coping with phobic stressors were measured within an intrasubject control design that included a baseline phase, an efficacy-acquisition phase, and a maximal-efficacy phase. In each of these phases, perceived coping self-efficacy, level of autonomic and endocrine activation, and several components of the immunological system were measured. Development of strong perceived self-efficacy to control phobic stressors had an immunoenhancing effect. A slow growth of perceived self-efficacy, heart rate acceleration, and cortisol activation attenuated immunological system status during the efficacy-acquisition phase. Rapid growth of perceived self-efficacy also predicted maintenance of immunoenhancement during the maximal perceived self-efficacy phase.

Adaptation, Psychological↗
PubMed1990

Normal T lymphocyte function in patients with end-stage renal disease hemodialyzed with 'high-flux' polysulfone membranes.

T lymphocyte function was analyzed in patients hemodialyzed with 'high-flux' polysulfone membranes, which have been reported to improve the patients' overall clinical condition and well-being. For comparison purposes, patients treated by the use of 'low-flux' cuprophane membranes were also studied. Peripheral blood white cell counts, numbers of lymphocytes as well as the numbers of T cells and their CD4 and CD8 subsets were within normal range in both patient groups. The absolute number of B cells was slightly decreased in cuprophane-membrane- but not polysulfone-membrane-treated patients. The proliferative response of T lymphocytes after stimulation with optimal concentration of phytohemagglutinin (PHA) was normal in patients treated with 'high-flux' membrane dialysis but significantly reduced in those treated with cuprophane membranes. The generation of interleukin-2 (IL-2) receptor on T lymphocytes after PHA stimulation was normal in the polysulfone-membrane-treated group and slightly impaired in the cuprophane-membrane-dialyzed patients. Production of both IL-2 and interleukin-1, as well as the natural killer cell activity, in patients treated by 'high-flux' membrane dialysis were also comparable to controls. The levels of serum beta 2-microglobulin were significantly elevated in patients-maintained on 'high-flux' dialysis membranes but did not reach the levels seen in patients dialyzed by cuprophane membranes. The beta 2-microglobulin at levels seen in patients on cuprophane dialysis had no effects on activation and proliferation of control lymphocytes in vitro. These results suggest that impaired functional responses of T lymphocytes seen in end-stage disease patients on prolonged hemodialysis with cuprophane membranes are not seen in similar patients hemodialyzed with polysulfone membranes.

Biocompatible Materials↗
PubMed1990

Combined utility of gene rearrangement analysis and flow cytometry in the diagnosis of lymphoproliferative disease in the bone marrow.

The diagnosis of lymphoma involving bone marrow is often complicated by the presence of nonspecific lymphoid aggregates. Morphologic criteria may not permit the distinction of benign from malignant lymphoid aggregates with certainty in all cases. We combined morphology with immunophenotypic and immunogenotypic analyses of aspirated marrow cells to develop more reliable criteria for the diagnosis of marrow involvement by lymphoma. The presence of morphologically recognizable lymphoma cells in the bone marrow aspirate was always confirmed by immunogenotypic analysis. The yield of either immunophenotypic or immunogenotypic analyses on morphologically negative marrows was very low. Focal paratrabecular involvement by lymphoma was not always confirmed by immunophenotypic or immunogenotypic analyses, probably due to sampling error and factors interfering with aspiration of the lymphoid aggregates. Thus, the immunologic and molecular studies supported, but did not substantially improve upon the morphologic criteria that are in common usage for distinguishing benign from malignant lymphoid aggregates in the bone marrow. Finally, evidence of B-lymphocyte clonality was obtained in four of five cases in which there were nonspecific lymphoid aggregates in the bone marrow in the absence of otherwise clinically definable malignancy.

Aged↗
PubMed1989

Chimerasome-mediated gene transfer in vitro and in vivo.

Proteoliposome delivery vesicles can be prepared by the protein-cochleate method [Gould-Fogerite and Mannino, Anal. Biochem. 148 (1985) 15-25; Mannino and Gould-Fogerite, Biotechniques 6 (1988) 682-690]. Proteins which mediate the entry of enveloped viruses into cells are integrated in the lipid bilayer, and materials are encapsulated at high efficiency within the aqueous interior of these vesicles. We describe proteoliposome-mediated delivery of proteins and drugs into entire populations of cells in culture. Material can be delivered gradually by Sendai-virus-glycoprotein-containing proteoliposomes. Alternatively, synchronous delivery to a population can be achieved by exposing cell-bound influenza glycoprotein vesicles briefly to low pH buffer. When DNA is encapsulated, chimeric proteoliposome gene-transfer vesicles (chimerasomes), which mediate high-efficiency gene transfer in vitro and in vivo, are produced. Stable expression of a bovine papilloma virus-based plasmid in tissue-cultured cells, at 100,000 times greater efficiency than Ca.phosphate precipitation of DNA, with respect to the quantity of DNA used, has been achieved. Stable gene transfer and expression in mice has been obtained by subcutaneous injection of chimerasomes containing a plasmid expressing the early region of polyoma virus. In one experimental group, 50% of the mice developed tumors which were shown to express polyoma virus early proteins and contain the transferred DNA. This is the first report of stable gene transfer in animals mediated by a liposome- or proteoliposome-based system.

Animals↗
PubMed1989

The immune response to vaccinia virus infection in mice: analysis of the role of antibody.

Immune response to primary intraperitoneal infection with vaccinia virus (strain IHD-J) was studied in C3H/Hej mice. Antibodies reactive with virus structural proteins were detected 6 days and neutralizing antibodies 8 days after infection. Although serum antibodies from infected mice bound to vaccinia virus infected cells, these antibodies were ineffective in complement mediated lysis of infected cells and were only moderately active in experiments with antibody dependent cellular cytotoxicity (ADCC). Immunoblotting analysis showed that serum antibody reacted with a number of structural proteins of both intracellular and extracellular forms of vaccinia virus. Immunoprecipitation results showed antibody binding of nonstructural proteins and glycoproteins. Correlation of the kinetics of NK and CTL activities in infected mice with neutralizing antibodies indicated that the cellular functions clearly precede the appearance of serum neutralizing antibody. The resolution of primary infection in mice thus appears to be mediated by functions of cellular immunity while resistance to reinfection may be dependent on circulating neutralizing antibody.

Animals↗
PubMed1989

Ultrastructural immunolocalization of cyclin/PCNA in synchronized 3T3 cells.

The immunolocalization of cyclin/PCNA in synchronized 3T3 cells was performed with human autoantibodies using an immunogold technique performed on thin cryosections. Previous immunofluorescent studies demonstrated that the DNA replication sites correspond to the localization of bound cyclin. We have found that in the early periods of S phase, the DNA replication sites (or sites potentially ready for the replication during the hydroxyurea DNA synthesis block) are situated in the perichromatin region and correspond to clustered gold particles present frequently over a morphologically distinct small nuclear area. Heavily labeled chromocenters, including perinucleolar condensed chromatin, exhibiting several such distinct areas were found in later periods of S phase.

Animals↗
PubMed1989

C-terminal domain of the adenovirus E1A oncogene product is required for induction of cytotoxic T lymphocytes and tumor-specific transplantation immunity.

Adenovirus genes required for the elicitation of adenovirus group C-specific cytolytic T lymphocytes (CTLs) and for the induction of adenovirus-specific transplantation antigen (TSTA) were identified by immunization with a library of adenovirus mutants. The group C Ad-specific CTL response was elicited by immunization with wild-type adenovirus type 5 (Ad5) or with recombinant adenoviruses containing Ad5 E1A gene. The specific CTL response was also elicited by Ad5 virus constructs which express only the 12 S or 13 S E1A early mRNA, but not with viruses unable to express E1A protein sequences normally encoded by the E1A early messages. The induction of transplantation immunity against tumorigenic Ad-transformed cells was studied next. The product encoded by either 13 S and 12 S E1A mRNA alone was sufficient for strong TSTA activity. A series of viruses with mutations within the first exon of the E1A message also induced strong TSTA, while Ad5 mutants with lesions within the second exon failed to induce syngraft immunity. These results provide strong evidence that amino acid sequence encoded by the second exon of the Ad5 E1A message is required, either directly or indirectly, for the induction of both Ad-specific CTL and Ad TSTA.

Adenovirus Early Proteins↗
PubMed1989

Plasma cell malignancy in the acquired immune deficiency syndrome. Association with Epstein-Barr virus.

The development of high-grade, malignant B-cell lymphoma is a well-recognized complication of human immunodeficiency virus (HIV) infection. Plasma cell neoplasms, however, have been rarely encountered in HIV-infected people. This study presents the morphologic and immunologic features of an unusual plasma cell tumor occurring in a 31-year-old HIV-antibody-positive male. The malignancy was characterized by widespread dissemination and hypercalcemia at presentation and a clinically aggressive course. Immunoperoxidase staining of tumor tissue obtained from biopsy and at autopsy had positive results for IgM and lambda. In the patient's serum, only an IgG kappa paraprotein was detected, indicating that the tumor was nonsecretory. DNA analysis of autopsy-derived tumor tissues demonstrated clonal rearrangements of the immunoglobulin (Ig) heavy chain gene locus and rearrangements in both kappa and lambda light chain gene loci. Furthermore, DNA hybridization studies revealed the presence of Epstein-Barr virus (EBV) genomes in tumor tissue but not in nontumor tissue from this patient.

Acquired Immunodeficiency Syndrome↗