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Biomedical subjects

J Raskova

Publications and source records attributed to J Raskova.

At least 37 records · Page 2Linked to original sources
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

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

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↗
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

Human immunodeficiency virus (HIV) infection in haemophiliacs: long-term prognostic significance of the HIV serologic pattern.

To identify markers of prognostic value in the course of HIV disease, immunologic parameters and profiles of HIV antibodies and antigen were studied in 60 haemophiliacs. The 43 HIV-seropositive subjects were followed prospectively over a 4 year period with a retrospective analysis as well of their frozen plasma for HIV markers. This group had a significant decrease in number of helper/inducer T lymphocytes as compared with 17 HIV seronegative subjects. The degree of changes correlated with the stage of disease, with the most severe depletion of CD4 cells in those who developed AIDS. Counts of B cells and platelets were also lower in HIV-infected haemophiliacs. Ten out of 12 AIDS patients had undetectable antibodies to HIV p24 antigen; low levels of p24 antibody were also seen in six out of 15 subjects with lymphadenopathy (CDC stage III), but in only two out of 16 asymptomatic subjects (CDC stage II). Sustained HIV p24 antigenaemia (greater than 30 pg/ml) was seen in 10 AIDS patients, in five subjects with lymphadenopathy and in two asymptomatic haemophiliacs. Initial HIV serologic profiles, obtained when all patients were asymptomatic, were highly predictive for progression of the HIV infection: the initial pattern of low anti-p24 antibody and positive p24 antigenaemia conferred the worst prognosis, with all patients in this group developing ARC or AIDS within 36 months, whereas an initial high level of anti-p24 without p24 antigenaemia was associated with relatively the best prognosis. Of such subjects, 58% have remained clinically asymptomatic after 48 months of the study (P less than 0.00001). The serologic profile of HIV antibody pattern and HIV antigen in haemophilic patients thus already provides important prognostic information at an early stage of HIV infection.

AIDS Serodiagnosis↗
PubMed1989

Independent learning in pathology. Does it work?

The sophomore pathology course at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, was substantially modified with the intention of promoting guided, independent learning. The emphasis has been shifted from lectures to other modalities of instruction. This article delineates the curricular changes made, describes the instructional modalities used, and reports student performance after two year's experience with the new curriculum.

Education, Medical, Undergraduate↗
PubMed1987

B-cell activation and immunoregulation in end-stage renal disease patients receiving hemodialysis.

B-lymphocyte functions were studied in peripheral blood mononuclear cells of end-stage renal disease patients undergoing intermittent hemodialysis for longer than two years. T-cell-dependent B lymphocyte proliferation after pokeweed mitogen stimulation was low in half of the hemodialyzed patients. T cell-independent B cell response to Staphylococcus aureus, Cowan I, was also significantly reduced. Spontaneous production of immunoglobulin in cultures of peripheral blood mononuclear cells of uremic patients was comparable with that of healthy controls, but pokeweed mitogen-stimulated antibody secretion was significantly reduced with cells from patients undergoing hemodialysis. Helper T-cell functions in B-cell activation were also qualitatively deficient in uremic patients. It is concluded that B-cell activation and immunoregulation is defective in patients undergoing long-term hemodialysis.

Adult↗
PubMed1986

Adenovirus tumor-specific transplantation antigen is a function of the E1A early region.

Viable recombinant adenoviruses that carry a portion of the type 12 E1A and E1B transcription units in a type 5 background were used to identify genes controlling expression of the adenovirus tumor-specific transplantation antigen (TSTA). The TSTA immunity is not crossreacting between the group A and group C adenovirus serotypes. Viruses carrying the E1A region (sub370-12E1A), or both E1A and E1B (sub370-12E1AB) regions of Ad12, induce a strong transplantation immunity against tumors induced by syngeneic cells transformed with adenovirus 12, but fail to induce any protection against syngeneic cells transformed with adenovirus 2. Immunization with the virus carrying only the E1B region (sub370-12E1B) of adenovirus 12 induces no immunity to adenovirus 12 transformed cell line, but confers a strong protection against cells transformed with adenovirus 2. These results provide strong evidence that the adenovirus tumor-specific transplantation antigen is a function of the E1A early region.

Adenovirus Early Proteins↗
PubMed1986

T cells in patients undergoing chronic hemodialysis: mitogenic response, suppressor activity, and interleukin-2 production and receptor generation.

The functional response of peripheral blood T lymphocytes was studied in patients with end-stage renal disease treated by chronic hemodialysis for over 1 year. Proliferation after phytohemagglutinin stimulation of patients' peripheral blood mononuclear cells and of T lymphocyte fractions isolated by either sheep erythrocyte rosetting or by use of a nylon wool column was significantly reduced as compared with that of corresponding fractions from healthy control subjects (P less than 0.001). The induction of suppressor cell activity by concanavalin A in rosetted T cell fractions was higher with cells of hemodialyzed patients than with control cells (P less than 0.025). The expression of class II MHC antigen (HLA-DR) by the T8 lymphocyte subset after concanavalin A induction, as determined by staining with monoclonal antibodies and two-color fluorescence analysis by flow cytometry, was also higher in hemodialyzed subjects (P less than 0.025). Since contamination by non-T cells in such cell fractions and increases in proliferation after indomethacin treatment of peripheral blood mononuclear cells were similar in hemodialyzed and control subjects, it is unlikely that the depressed T lymphocyte responses and the increased suppressor cell activity can be attributed to increased peripheral blood monocyte counts observed in patients undergoing hemodialysis. Studies of the biological events associated with the activation of lymphocytes of hemodialyzed patients revealed a reduction in expression of interleukin 2 receptor in the plasma membrane of phytohemagglutinin-stimulated lymphocytes as determined by staining with monoclonal antibody (P less than 0.01). In addition, a very low secretion of interleukin 2 by stimulated peripheral blood mononuclear cell populations was observed in about one-half of patients receiving hemodialysis.

Adult↗
PubMed1986

Cellular immunity and lymphocyte populations in developing uremia in the rat.

Changes in cellular immunity and in lymphocyte populations have been studied in rats developing chronic renal insufficiency following 5/6 nephrectomy. Animals remain stable for a period of six months (BUN 40-60 mg/dl); then BUN slowly increases for 2-3 months, followed by rapid deterioration and death of the animals. Skin allotransplants showed no change in survival when transplanted fifteen weeks after nephrectomy; when transplanted 22 weeks and later after surgery, their survival was prolonged. The response of splenic cells in the mixed lymphocyte reaction (MLR) was unchanged for 15 weeks after surgery but became significantly reduced after 20 weeks. At the same time we observed an increased suppressor cell activity in splenic cell suspensions and an inhibitory effect of the uremic serum in the MLR. Resistance to tumor induction by syngeneic adenovirus 12-transformed cells was decreased in the late stages of uremia as measured by tumor development in these animals. Induction of cytolytic T cells in vitro was reduced at 24 weeks after operation; at 30 weeks virtually no cytolytic T cell activity was induced. There was also a decrease in natural killer cell activity in the late stages of uremia. These changes in immune response were correlated with the analysis of the lymphocyte sub-populations by staining with monoclonal antibodies and flow cytometry. During the development of uremia no significant changes were found in the lymph nodes. The thymus underwent a severe involution 20 weeks and later after nephrectomy. In the peripheral blood there was a significant decrease in the numbers of helper T cells. The helper T cell subset was also sharply reduced in the spleen of uremic rats at 20 weeks and later after operation.

Aging↗
PubMed1985

Glomerular morphometry in the Munich-Wistar rat.

Physiological studies of glomerular function in the rat have been much advanced by the accessibility of superficial glomeruli for micropuncture in a mutant strain, the Munich Wistar (MW) rat. An important parameter studied in this way is the glomerular ultrafiltration coefficient, or Kf. Kf is the product of hydraulic permeability and of the effective filtration surface area. Confounding factors are the variation in anatomical glomerular filtration surface in the rat with body weight (BW) and with the anatomical position of the glomerulus. To establish appropriate anatomical values for the interpretation of Kf in the MW rat, we have carried out a morphometric study by electron microscopy of two groups of relatively mature male MW rats, of approximately 200 g and approximately 300 g BW respectively. We find that superficial cortical (SC) and midcortical (MC) glomeruli of MW rats of approximately 200 g BW have relatively low glomerular volumes and anatomical filtration surface areas, but that MW rats of approximately 300 g BW have larger SC and MC glomeruli of similar size to juxtamedullary (JM) glomeruli, and anatomical filtration surface areas comparable to values usually assumed in physiological studies. We ascribe this contrast between SC glomeruli of MW rats of approximately 200 g and approximately 300 g BW respectively to the maturation of SC glomeruli.

Animals↗
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↗