Biomedical subjects

C C Kurman

Publications and source records attributed to C C Kurman.

32 records · Page 2Linked to original sources

PubMed1988

Elevated concentrations of soluble interleukin-2 receptors in serum samples and bronchoalveolar lavage fluids in active sarcoidosis.

Sarcoidosis is a granulomatous disorder of unknown cause characterized by activation of T-lymphocytes. We here report the use of an enzyme-linked immunosorbent assay for the soluble interleukin-2 receptor (IL-2R) as a measure of T-cell activation in serum samples and bronchoalveolar lavage fluids in 15 patients with active sarcoidosis. The geometric mean (x divided by SEM) value for soluble IL-2R in serum samples from patients with sarcoidosis was 1,110 (x divided by 1.17) versus 224 (x divided by 1.08) U/ml for normal control subjects (p less than 0.001). Detectable levels of soluble IL-2R were present in bronchoalveolar lavage fluids from 10 of 15 patients with sarcoidosis versus only 2 of 36 normal control subjects (p less than 0.001). Levels of soluble IL-2R in serum samples from untreated patients with sarcoidosis correlated with 67gallium lung scanning scores (p less than 0.05) but not with serum angiotensin-converting enzyme concentrations or constituents of bronchoalveolar lavage. In 5 patients, the level of soluble IL-2R in serum samples fell from 1,499 (x divided by 1.20) to 476 (x divided by 1.58) U/ml (p less than 0.05) after 6 wk of successful treatment with corticosteroids, whereas the changes in soluble IL-2R in bronchoalveolar lavage fluids were more variable. These observations suggest that measurements of soluble IL-2R, particularly in serum samples, may reflect disease activity and be clinically useful in the management of patients with sarcoidosis.

Adrenal Cortex Hormones↗

PubMed1988

Soluble Tac peptide is present in the urine of normal individuals and at elevated levels in patients with adult T cell leukaemia (ATL).

The T lymphocyte-derived lymphokine interleukin 2 and the cell-associated receptor for this molecule play major roles in the activation and regulation of the human immune response. An enzyme-linked immunosorbent assay has been developed to measure quantitatively a soluble form of one component of the human interleukin 2 receptor, namely the Tac peptide. In the present studies, soluble Tac peptide was measured in the urine of normal individuals (mean = 92 U/ml), a level not significantly different (0.01 less than P less than 0.05) from the corresponding serum concentrations (mean = 175). The urinary Tac peptide had a molecular weight of 40-45 kD by sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis and specifically bound interleukin 2. Elevated levels of urinary Tac peptide were found in four patients with adult T cell leukaemia who also had elevated serum levels of Tac peptide. Thus, urine may represent a valuable source of lymphokine-binding proteins that may serve as important markers of immunological activation.

Adult↗

PubMed1987

Elevated serum levels of soluble interleukin-2 receptors in active pulmonary sarcoidosis: relative specificity and association with hypercalcemia.

We have previously reported serum elevations of the soluble form of the interleukin-2 receptor (IL-2R), a marker of T-cell activation, in sarcoidosis. In the present study, an enzyme-linked immunosorbent assay for soluble IL-2R was employed to compare sera from normal controls with those from patients with active sarcoidosis or idiopathic pulmonary fibrosis (IPF). Sera from patients with active sarcoidosis and parenchymal lung disease (radiographic Stages II or III) had geometric mean values for soluble IL-2R of 1975 units/ml compared to 640 units/ml for normal controls (p less than 0.001, Student's t-test). By contrast, soluble IL-2R levels were lower (989 units/ml, p less than 0.05 compared to normals) in patients with active sarcoidosis but no radiographic evidence for parenchymal disease (Stages 0 or I). Soluble IL-2R levels were not elevated in patients with inactive sarcoidosis. Three of the 4 sarcoidosis patients with the highest levels of soluble IL-2R also manifested hypercalcemia. While levels of soluble IL-2R were elevated for the group of patients with IPF (1171 units/ml, p less than 0.05 compared to normals), the striking elevations of soluble IL-2R noted in active sarcoidosis were not seen and there was greater overlap with normal values. We conclude that marked serum elevations of soluble IL-2R are more suggestive of active pulmonary sarcoidosis than IPF.

Adrenal Cortex Hormones↗

PubMed1986

An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets.

B-Lymphocytes↗

PubMed1986

The production of soluble and cellular interleukin-2 receptors by cord blood mononuclear cells following in vitro activation.

Cord blood mononuclear cells (CBMC) were investigated for their capacity to generate both cellular and soluble, supernatant interleukin-2 receptors (IL-2R) following cellular activation in vitro. Soluble IL-2R were measured in cell-free supernatants and in detergent-solubilized cell extracts with a "sandwich" enzyme-linked immunosorbent assay. CBMC and adult peripheral blood mononuclear cells were activated with phytohemagglutinin or the murine monoclonal antibody OKT3. CBMC and adult peripheral blood mononuclear cells generated cellular and soluble IL-2R in response to both activators. Peak values for supernatant IL-2R were observed on day 7, while peak values of cell-associated IL-2R occurred on day 5, followed by a decline on day 7. With the exception of supernatant IL-2R production induced by OKT3 stimulation, CBMC produced IL-2R in amounts comparable to adult mononuclear cells. Cord blood plasma also contained amounts of IL-2R comparable to that found in adult sera/plasma. Thus, CBMC appear largely immunocompetent with regard to the expression of IL-2R.

Adult↗

PubMed1985

A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac.

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.

Antibodies, Monoclonal↗

PubMed1985

Defective specific antiinfluenza virus antibody production in vitro by lymphocytes from patients with ataxia-telangiectasia.

The ability of lymphocytes from 11 patients with ataxia-telangiectasia to produce specific antiinfluenza virus antibody in vitro was evaluated. Lymphocytes from these patients produced markedly less antibody than lymphocytes from normal controls when stimulated with type A influenza viruses. Additional studies were undertaken to evaluate the function of the B cells, T cells, and adherent cells of these patients in specific antibody production. B cells from the AT patients produced one-third to one-half as much antiinfluenza virus antibody as did B cells from normals when stimulated with the polyclonal activator Epstein-Barr virus or, in the two cases studied, when stimulated with influenza virus in the presence of normal HLA-identical T-cells, suggesting that a partial B-cell defect contributed to the deficient antibody response in these patients. Helper T-cell function of T-cells from two patients was evaluated in coculture with their HLA-identical sibling's B cells; these studies revealed that the patients' T-cells could provide less help than normals' T-cells but that this help was not entirely deficient. Furthermore, T-cells from AT patients could provide allostimulated helper T-cell function in coculture with allogeneic normal B cells. Taken together, these results suggest that partial defects of B- and T-cell function both contribute to the decreased antiinfluenza virus antibody production by patients with AT.

Adolescent↗

PubMed1985

Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro.

With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R released from either the HTLV I-positive T cell line HUT 102B2 or normal phytohemagglutinin-activated PBMC demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.

Cell Division↗

PubMed1984

Antigen-stimulated human B cell clones are committed to the production of a single class of antibody in vitro.

We have investigated the isotype(s) of antibody produced in vitro by antigen-stimulated human B cell clones. An analysis of the class(es) of antibody produced in multiple replicate cultures containing a mean of less than one precursor B cell per well was consistent with the hypothesis that individual B cell precursors produced a single class of antibody. This result was obtained by using cells isolated from either the peripheral blood or tonsils. Thus, under the culture conditions utilized, no intraclonal isotype switching was detected.

Antibodies, Viral↗

PubMed1984

Active immunization of hamsters against pancreatic carcinoma with lipid-treated cells or their shed antigens.

Increasing membrane lipid microviscosity of cells by treatment with cholesterol esters such as cholesterol hemisuccinate (CHS) enhances immunogenicity, probably by exposure of cryptic membrane antigens. Transplantable pancreatic carcinoma lines CBP and LSP-1 grown in inbred hamsters were tested for immunogenicity after CHS treatment. Tumor cells were incubated in CHS to rigidify cell membranes, and they were irradiated and injected i.p. into syngeneic hamsters. Incubation media after CHS treatment, considered to contain shed antigens due to hyperrigidification, were also used for immunization. Two identical immunizations using 10(7) cells or incubation media were performed 14 days apart. In control experiments, non-CHS-treated, irradiated cells were injected. Immunizations were performed using both syngeneic and allogeneic cells and supernatants for both the CBP and LSP-1 systems for specificity experiments. The degree of immunization in the treated hamsters was assessed by the response to a subsequent s.c. challenge with viable tumor cells given 7 days following the last immunization. For the CBP pancreatic cancer line, CHS treatment increased tumor immunogenicity significantly, as demonstrated by diminished tumor growth rate and by increased duration of survival after challenge. With the LSP-1 pancreatic tumor, immunization with CHS-treated cells showed no enhancement of immunogenicity. However, immunization with supernatant of CHS-treated cells resulted in a significant delay of tumor growth and increased survival, suggesting immunization by shed antigens in the CHS incubation medium. Use of CHS-treated cells or shed antigeneic material could be of potential value as a method of active immunotherapy.

Adenocarcinoma↗

PubMed1983

Demonstration of type-R and type-C virus particles in hamster pancreatic adenocarcinomas.

Two transplantable solid tumors (CBP and PDP) and two continuous cultured cell lines (CBP-TC and PDP-TC) were established from nitrosamine-induced pancreatic ductal adenocarcinomas in inbred Syrian hamsters. Electron microscopic examination of both CBP and PDP solid tumors as well as CBP-TC cultured cells revealed the presence of type-R virus particles, which consisted of a 100 nm envelope containing a central 50 nm nucleoid with characteristic radiating 'spokes'. Type-R particles were abundant in cultured CBP-TC cells, moderately frequent in CBP solid tumors, and rare in PDP solid tumors; they were not present in PDP-TC cultured cells. The CBP and PDP solid tumors and cultured PDP-TC cells exhibited type-C viral particles, having a 150 nm envelope containing a 75 nm nucleoid. Mature, immature and budding forms of Type-C viruses were present and quite prominent in PDP tumors. Type-C particles were present but rare in CBP solid tumors and in PDP-TC cells. C-particles were not observed in cultured CBP-TC cells. Examination of normal hamster pancreas, liver, duodenum, muscle and connective tissue failed to reveal evidence of type-R or type-C virus particles. It is important to recognize the presence of virus particles in hamster pancreatic carcinoma lines, since viruses could potentially affect biochemical or immunological studies on the carcinomas through the production of viral proteins that could be mistaken for tumor-associated antigens.

Adenocarcinoma↗

PubMed1982

Nitrosamine-induced pancreatic carcinogenesis in outbred and inbred Syrian hamsters.

Pancreatic carcinogenesis was investigated in outbred and in five strains of inbred Syrian golden hamsters utilizing the nitrosamines N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP). Thirty eight outbred hamsters were treated for an average of 15 weeks with weekly s.c. inoculations of BHP at doses of 250,000 or 1000 mg/kg. Pancreatic carcinomas developed in 19%. Eighty nine inbred hamsters of strains CB, LHC and PD4 were given BHP at 250 mg/kg weekly for an average of 25 weeks. Pancreatic carcinomas developed in 61%. Pancreatic inflammation, fibrosis, and ductal hyperplasia were prominent. Toxic changes in the liver, biliary hyperplasia, and pulmonary interstitial inflammation were also prominent features of BHP-treated hamsters, along with occasional carcinomas of the liver and respiratory tract. One hundred and sixteen inbred hamsters of strains CB, LHC, LSH, MHA, and PD4 were treated with BOP at a dose of 5 mg/kg weekly for 15 weeks. The incidence of pancreatic carcinoma was 51%. BHP-treated hamsters exhibited pancreatic fibrosis and ductal hyperplasia. Livers of BHP-treated animals showed biliary hyperplasia, and lungs exhibited chronic inflammation. Occasional carcinomas of the liver and lung developed. From 243 hamsters treated with nitroso carcinogens, eight pancreatic ductal adenocarcinoma lines were derived that can be transplanted and propagated in inbred hamsters.

Adenocarcinoma↗

PubMed1981

Nitrosamine-induced transplantable pancreatic ductal adenocarcinoma in inbred Syrian hamsters.

A pancreatic ductal carcinoma, designated CBP, was established as a transplantable tumor line in the CB/SsLak inbred strain of Syrian golden hamsters. The tumor, a primary one induced by chronic administration of the nitrosamine N-nitro-bis(2-hydroxyproyl) amine, is a well-differentiated adenocarcinoma that can be propagated by transplantation in syngeneic hamsters. It grows poorly in other hamster strains. The CBP tumor develops in a predictable quantitative manner and metastasizes to regional lymph nodes. Excision of primary transplanted tumor nodules leads to immunity against subsequent secondary tumor challenges. The CBP tumor appears to be a suitable model for biologic and immunologic studies of pancreatic carcinoma in the syrian hamster.

Animals↗

PubMedDate not supplied

Retinoic acid binding protein in human and experimental pancreatic carcinomas in hamsters.

Cytoplasmic retinoic acid binding protein (cRABP) is present in human fetal pancreas and becomes nondetectable in the normal adult pancreas. The binding protein for retinoic acid becomes apparent again in pancreatic cancer. Similar fluctuations in the content of cRABP occur in the hamster. The binding protein is undetectable in the normal adult hamster pancreas, while it was detected in several transplantable adenocarcinomas in the Syrian golden hamster.

Adenocarcinoma↗