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Biomedical subjects

K Raska

Publications and source records attributed to K Raska.

At least 55 records · Page 3Linked to original sources
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

Does the synthesis of ribosomal RNA take place within nucleolar fibrillar centers or dense fibrillar components?

By means of immunocytochemistry performed on cryosections of cultured cells, RNA polymerase I was localized mainly to nucleolar fibrillar centers. The labelling of nucleolar dense fibrillar components was low and depended on the cell type. In contrast, DNA topoisomerase I and RNP complexes containing U3 snRNA were enriched in dense fibrillar components, their occurrence in fibrillar centers being usually much less.

Adrenal Gland Neoplasms↗
PubMed1989

Immune thrombocytopenia in hemophiliacs infected with human immunodeficiency virus and their response to splenectomy.

We studied five patients with hemophilia A in the age range of 18 to 64 years who were infected with human immunodeficiency virus and who developed immune thrombocytopenia. The clinical course of immune thrombocytopenia in relation to human immunodeficiency virus infection and the patients' responses to splenectomy and immune variables were determined. All five patients developed antibody to human immunodeficiency virus 6 to 60 months (median, 24 months) before the onset of thrombocytopenia, and two patients became human immunodeficiency virus antigenemic (one patient at the onset of immune thrombocytopenia and the other 60 months after the onset of immune thrombocytopenia [24 months after splenectomy]). All five patients had a strong platelet-associated immunoglobulin G and three patients also had a weak platelet-associated immunoglobulin M on their platelets. In four of five patients danazol therapy failed, and three patients required moderate doses of prednisone. Because of the progression of immune thrombocytopenia, four of the five patients underwent splenectomy with preoperative high-dose intravenous immune globulin. All four had an excellent immediate response to splenectomy, with a rise in platelet count to more than 300 x 10(9)/L and sustained remission during postsplenectomy follow-up of 6 to 45 months. There was no significant drop in CD4 and CD8 counts after splenectomy, and all four patients remained clinically well.

Adult↗
PubMed1988

Adenovirus type 5 and adenovirus type 12 recombinant viruses containing heterologous E1 genes are viable, transform rat cells, but are not tumorigenic in rats.

Two sets of adenovirus type 5 (Ad5)-adenovirus type 12 (Ad12) recombinant viruses were constructed and analyzed. In one case the Ad12 E1A, E1B, or E1A plus E1B genes were substituted for the corresponding Ad5 genes in the Ad5 chromosome. The second set contained the Ad5 E1A, E1B, or E1A plus E1B genes in place of the cognate Ad12 genes in the Ad12 chromosome. The hybrid viruses were all viable and expressed the appropriate E1 antigens. They were able to transform secondary rat fibroblasts, but at reduced efficiency as compared to either parental virus. Fibroblasts transformed with the recombinant Ad5 virus carrying the Ad12 E1A plus E1B genes were tumorigenic in newborn, syngeneic rats. Some of the cell lines transformed with the Ad5 virus containing the Ad12 E1A gene were tumorigenic but none of the recombinants with the Ad12 E1B gene was able to induce tumors in this assay. Although Ad12 was tumorigenic, none of the Ad5 or Ad12 recombinant viruses induced tumors in newborn rats injected either intracerebrally or subcutaneously with virus particles.

Adenovirus Early Proteins↗
PubMed1988

Human immunodeficiency virus infection in sexually active wives of infected hemophilic men.

PURPOSE: Because of past multiple exposures to contaminated coagulation factor concentrates, the prevalence of human immunodeficiency virus (HIV) infection among adult hemophilic men in the United States is reported to range from 75 to 90 percent. The risk of HIV transmission through a long-term monogamous heterosexual contact can be estimated by studying the spouses of hemophilic subjects since these couples generally do not abuse intravenous drugs, usually maintain stable monogamous relationships, and are usually free of other risk factors. Our purpose was to gather data on the risk of heterosexual transmission of HIV infection in the context of long-term monogamous relations according to the duration of HIV antibody seropositivity and of HIV antigenemia in HIV-infected hemophilic men, and their sexual habits. SUBJECTS AND METHODS: Infection with HIV was studied in 14 sexually active spouses of infected hemophilic men who had been HIV antibody reactive for a mean of 46 +/- 23 (SD) months. One half of the hemophilic men studied had overt HIV antigenemia for a mean duration of 27 +/- 23 (SD) months; six of the men studied fulfilled clinical criteria for the diagnosis of acquired immunodeficiency syndrome (AIDS). All 14 couples were sexually active in a strictly monogamous fashion, in marriages of 13.5 +/- 10.5 (SD) years with an average reported frequency of four sexual encounters per month (range: one to 12). Plasma samples of the hemophilic husbands were retrospectively analyzed for HIV and hepatitis B virus markers. Blood samples were obtained from female spouses on at least two occasions, six months apart. Comprehensive questionnaires regarding sexual habits and other risk factors were filled out by each couple; during this interview, the couple was counseled about safe sexual practices. None of the couples studied used condoms prior to January 1986. RESULTS: Antibodies to HIV developed in only one of the 14 wives. At the time when this seroconversion was detected, her husband, in whom AIDS developed, had been reactive for HIV antibody for 49 months, and showed positive findings for HIV antigen for 26 months. No additional risk factors were identified for this couple. The infected female spouse, however, has a 14-year history of multiple sclerosis, and had been treated with immunosuppressant intermittently. Despite a significantly reduced number of CD4 lymphocytes, she has remained clinically asymptomatic for 17 months since seroconversion. HIV antibodies did not develop in any of the 13 remaining wives, despite the frequent practice of oral sex by six couples and reports of occasional anal intercourse by another couple.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

Clonal B-cell proliferation in an infant with congenital HIV infection and immune thrombocytopenia.

An infant with congenital human immunodeficiency virus (HIV) infection had immune thrombocytopenic purpura (ITP) develop at four months of age. A bone marrow aspirate had normal results in morphologic characteristics and cellularity. Flow cytometry analysis of the marrow cells showed that the predominant cell in the "lymphocyte" cluster was of B-lineage and common acute lymphocytic leukemia antigen (CALLA) positive. Southern blot analysis of marrow DNA demonstrated gene rearrangements in both the immunoglobulin (Ig) heavy chain and kappa light chain loci, confirming the presence of a clonal B-cell lymphoid proliferation. At one year of age the patient is clinically well without evidence of malignant lympho-proliferative disease. This case exemplifies a limited clonal B-cell expansion in the bone marrow of a patient with HIV infection and a benign hematologic condition.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Tumorigenicity of adenovirus-transformed cells: collagen interaction and cell surface laminin are controlled by the serotype origin of the E1A and E1B genes.

A library of cells transformed with recombinant adenoviruses was used to study tumorigenicity and interaction with extracellular matrix. Cells expressing the complete E1 region of highly oncogenic adenovirus type 12 (Ad12) are tumorigenic, adhere preferentially to type IV collagen, and express cell surface laminin. Weakly tumorigenic cells, which express the E1A oncogene of Ad12 and the E1B genes of Ad5, also attach preferentially to type IV collagen but do not contain laminin on their surface. Cells which express the E1A oncogene of Ad5 and the E1B genes of Ad12 are nontumorigenic and do not preferentially attach to type IV versus type I collagen but have laminin on their surface. There is no significant difference in the amounts of laminin secreted into the culture medium among cells expressing the E1B genes of Ad5 or Ad12. In vitro assays show that cells which express the E1B genes of Ad12, irrespective of the origin of the E1A genes, can bind three times more exogenously added laminin than cells expressing the E1B genes of nononcogenic Ad5. The interaction of adenovirus-transformed cells with collagen is controlled by the serotype origin of the E1A oncogene, whereas cell surface laminin is controlled by the serotype origin of the E1B genes.

Adenoviruses, Human↗
PubMed1987

Natural history of acquired immunodeficiency syndrome in hemophilic patients.

During the 5-year period from 1981 to 1985, we have observed 8 cases of acquired immunodeficiency syndrome (AIDS) among our 85 patients with hemophilia A. Thus, the prevalence of AIDS with hemophilia A is 9.4% in our patient population. By utilizing stored serum or plasma samples dating back to 1978, antibody against HTLV-III was detected in all 8 cases with AIDS. Based on the time interval from the appearance of antibody to HTLV-III to the diagnosis of AIDS in these patients, the incubation period ranged from 27 months to 60 months, with a median of 36 months. Before the diagnosis of full-blown AIDS, all patients exhibited a variety of prodromal manifestations of non-specific nature, including weight loss, oral candidiasis, unexplained non-productive chronic cough, generalized lymphadenopathy, and thrombocytopenia lasting several months to several years. Serial T-lymphocyte subset studies were available in some patients during the HTLV-III seropositive period and showed progressive lymphopenia, depletion of T4 cells with an average absolute count of 94 +/- 128 per mm3 (mean +/- 1 S.D.), and a markedly reversed T4/T8 ratio of 0.26 +/- 0.19 (mean +/- 1 S.D.). These findings suggest that the incubation period of AIDS is considerably long and that prospective study of serial immunologic markers and HTLV-III markers may be warranted in hemophilic patients at risk.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed1987

Expression of varying portions of the adenovirus 12 early region 1 in transformed cells affects tumorigenicity and interaction with extracellular matrix components.

Seven syngeneic rat cell lines transformed with the EcoRI-C (0 to 16.5 map units), SalI-C (0 to 10.3 map units), HindIII-G (0 to 6.8 map units), or AccI-H (0 to 4.7 map units) DNA fragments of highly oncogenic adenovirus 12 were tested for their tumorigenicity in syngeneic hosts and for their interaction with extracellular matrix components. Three of the cell lines (RFC1, EcoC-3, and SalC) were highly tumorigenic and induced tumors with a short latency period; two cell lines (HindG-2 and AccH-1) were also tumorigenic, but the latency period was significantly longer. The HindG-3 and AccH-4 cell lines were nontumorigenic. Collagen attachment preference was analyzed. All five tumorigenic cell lines showed a striking preference for type IV versus type I collagen in attachment assays. The nontumorigenic cell lines showed no preference for either type of collagen. Immunofluorescence analysis of the glycoprotein attachment factors laminin and fibronectin revealed a positive correlation between tumorigenicity, expression of the adenovirus 12 E1 region, and the amount of cell surface laminin. All of the cell lines displayed similar amounts of fibronectin on their surfaces. A similar correlation was observed with the laminin and fibronectin that was secreted into the culture medium. The highly tumorigenic cell lines secreted the greatest amount of laminin, while the nontumorigenic cell lines secreted the least. All of the cell lines secreted comparable amounts of fibronectin into the medium. The results suggest that preference for type IV collagen as well as the presence of cell surface laminin and its secretion are properties associated with expression of the E1 region of highly oncogenic adenovirus 12 in tumorigenic transformed cells.

Adenoviruses, Human↗
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

Region E1a of highly oncogenic adenovirus 12 in transformed cells protects against NK but not LAK cytolysis.

The sensitivity of a library of adenovirus-transformed rat cell lines to lysis with highly enriched populations of rat NK cells and LAK cells activated in vitro by culture with recombinant human IL-2 was studied and correlated with the tumorigenic potential of these cell lines. The cell lines studied express the transforming E1 region of highly oncogenic Ad12 or nononcogenic Ad2. Two cell lines express recombinant E1A regions. In one the E1A genes were of Ad12 origin and the E1B region was derived from nononcogenic Ad5. In the other, the E1A region was from Ad5 and the E1B genes from Ad12. All cell lines tested which express the early region E1 of Ad12 are tumorigenic in syngeneic rats. The two cell lines which express only the E1A or the E1B genes of Ad12, and the Ad2-transformed cells did not induce tumors. Transformed cell lines which express the E1A region of nononcogenic Ad2 or Ad5 are efficiently killed by rat NK cells, but cells which express the Ad12 E1A genes are resistant to lysis by NK-enriched cell fractions even at high effector:target ratio; cells containing the Ad12 E1 region are also resistant to IFN-activated NK cells. Although such NK-resistant cells have a uniformly low level of class I MHC antigen, their resistance is not affected by MHC antigen level modulation by rat IFN. Ad12-transformed cells resistant to endogeneous NK cells, however, are efficiently lysed by LAK cells stimulated in vitro by recombinant IL-2. Sensitivity to LAK killing is unaffected by IFN treatment of target cells. These results show that expression of the E1A region of highly oncogenic Ad12 in the transformed cells, which confers resistance to endogeneous NK cells, fails to protect against lysis by LAK cells.

Adenovirus Early Proteins↗
PubMed1986

Diffuse large-cell lymphoma with monoclonal IgM kappa and cold agglutinin.

A patient with diffuse large-cell lymphoma associated with a serum monoclonal IgM kappa and a cold agglutinin is described. The cold agglutinin was the initial manifestation of disease and was apparent for at least two months before the diagnosis of lymphoma. The lymphoma cells had surface and cytoplasmic IgM kappa.

Agglutinins↗
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↗