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D Cavanagh

Publications and source records attributed to D Cavanagh.

296 records · Page 17Linked to original sources
PubMedDate not supplied

Serum soluble interleukin-2 receptor alpha levels in patients with gynecologic cancers: early effect of surgery.

PROBLEM: To determine the early effect of abdominal cytoreductive surgery on serum soluble interleukin-2 receptor alpha (sIL-2R alpha) levels in patients with ovarian and cervical cancer, and to determine if the extent of cytoreduction correlated with the changes in serum sIL-2R alpha. METHOD: Thirty-nine patients with gynecologic cancer had serum sIL-2R alpha measured by enzyme-linked immunosorbent assay before abdominal cytoreductive surgery and once in the early postoperative period. RESULTS: Only patients with advanced epithelial ovarian cancer had elevated preoperative serum sIL-2R alpha levels. In 20 of 25 ovarian cancer cases (80%) and 10 of 14 cervical cancer cases (71.4%) the postoperative serum sIL-2R alpha levels exceeded the preoperative level (P = .003 and P = .011, respectively). Overall, the mean postoperative serum sIL-2R alpha level was greater than the preoperative level (P = .0001). CONCLUSION: Patients with early stage gynecologic cancer did not have elevated serum sIL-2R alpha levels before surgery. In the early postoperative period the serum sIL-2R alpha level was increased, which may be a nonspecific response to the trauma of surgery. Soluble IL-2R alpha may be one of the factors responsible for the immunosuppression in the early postoperative period, but may also herald a surge of activated T cells.

Blood Chemical Analysis↗
PubMedDate not supplied

Use of the Cytobrush for cervical sampling after cryotherapy.

The presence of endocervical cells in routine gynecologic smears (prepared from spatula and cotton swab samples) and Cytobrush smears was analyzed in 52 patients with a history of prior cryotherapy. These cases represented 11% of the 491 women evaluated using both techniques between August 1, 1987, and January 31, 1990. The routine smear contained endocervical cells in 25 (48%) of the 52 cases while the Cytobrush smear contained endocervical cells in 49 (94%) of the cases. The use of the Cytobrush for cervical cytologic screening thus appears to be of value in patients with a prior history of cryotherapy, which frequently renders the transformation zone less accessible to routine sampling.

Adolescent↗
PubMedDate not supplied

Monoclonal antibody and nucleic acid probes for the diagnosis of avian diseases.

Various properties of monoclonal antibody (MAB) and nucleic acid (NA) probes confer advantages over polyclonal antibodies in sera and permit the probes to be used to directly and rapidly detect small quantities of pathogens in body fluids, biopsy, or postmortem material. This makes it unnecessary to amplify the amount of pathogen by growth in vitro or to perform neutralization tests, procedures that are time-consuming. Even if pathogens are grown in vitro, highly specific MABs can be used in immunofluorescence tests to differentiate isolates to extents not possible using antisera. There has been much greater investment in the development of probes for the diagnosis of human disease than for veterinary disease, because of the greater commercial potential of the former. A number of factors work against the development and distribution of new probes, but most of these are only temporary impediments if demand is there. Even in human medicine, the application of new probes is in its infancy, and it is probable that it will be several years yet before probes achieve widespread use in avian diagnosis. However, the potential of some MAB and NA probes is too great to ignore.

Animals↗
PubMedDate not supplied

Expression of interleukin-2 receptor alpha (IL-2R alpha) mRNA and protein in advanced epithelial ovarian cancer.

Advanced epithelial ovarian cancer has recently been identified by us to be associated with elevated serum and ascitic levels of the soluble Interleukin-2 receptor alpha (sIL-2R alpha). To determine the cellular source of sIL-2R alpha, the expression of IL-2R alpha was assessed at the mRNA and protein level in peripheral blood mononuclear cells (PBMC), in ovarian cancer ascitic cell infiltrates and in primary and metastatic epithelial ovarian cancer lesions by immunochemistry, by flow cytometric analysis and by in situ hybridization (ISH). Normal PBMC and the PBMC from ovarian cancer patients had a low or undetectable level of IL-2R alpha mRNA and of IL-2R alpha cell-surface protein expression. Flow cytometric analysis of the heterogeneous ascitic infiltrates revealed few cells positively expressing cell-surface IL-2R alpha. By immunocytochemistry, 1-2% of leukocytes in the ascitic infiltrates were IL-2R alpha+. Cytologically these IL-2R alpha+ cells were lymphocytes. Frozen sections of primary and metastatic ovarian cancer lesions showed sparse lymphocytic infiltration and very small numbers of these tumour infiltrating lymphocytes (TIL) were IL-2R alpha+. In situ hybridization demonstrated that although less than 2% of leukocytes in the ascitic infiltrate had detectable levels of IL-2R alpha mRNA, there was a wide range in the level of mRNA expression in these positive cells. The cells expressing IL-2R alpha mRNA had the cytologic characteristics of lymphocytes. Similarly, in the frozen sections of the solid tumours, there was a range in the level of IL-2R alpha mRNA expression in the few TIL that expressed IL-2R alpha. Importantly, ovarian cancer cells and mesothelial cells did not express IL-2R alpha mRNA or IL-2R alpha protein. Our observations lead us to conclude that lymphocytes are the main, if not the only, source of sIL-2R alpha in ovarian cancer patients. Although cells expressing IL-2R alpha were relatively few in number, as the source of the high levels of sIL-2R alpha, they may contribute to the immunosuppression of ascitic lymphocytes in advanced epithelial ovarian cancer.

Ascites↗
PubMedDate not supplied

Interleukin-12 synergizes with interleukin-2 to generate lymphokine-activated killer activity in peripheral blood mononuclear cells cultured in ovarian cancer ascitic fluid.

OBJECTIVES: The ascites-associated lymphocytes in ovarian cancer have altered immunologic function, and cell-free ascitic fluid has immunomodulating properties. We determined (1) whether interleukin (IL)-2 could induce lymphokine-activated killer (LAK) activity in normal peripheral blood mononuclear cells (PBMC) cultured in ovarian cancer ascitic fluid, and (2) whether IL-12 could synergize with IL-2 to generate LAK activity in normal PBMC cultured in ascitic fluid. METHODS: Normal PBMC were cultured in control medium and in media consisting of 50% ascitic fluid (ascitic medium), with and without IL-2 and IL-12. Cell activation to assess LAK activity (cell lysis) was determined in a 51Cr-release assay with the tumor cell lines FMEX and SKOV3 as target cells. To determine a possible mechanism for any synergistic effect, the expression of perforin, a pore-forming protein, was determined by Northern blot analysis. RESULTS: Interleukin-2 alone could not induce LAK activity in normal PBMC cultured in 50% ascitic fluid for up to 3 days. Interleukin-12 did mediate some or minimal LAK activity after 1, 2, or 3 days of incubation in control medium or in 50% ascitic fluid. When IL-2 and IL-12 were used in combination, PBMC cultured for 3 days in 50% ascitic fluid had remarkably high lytic activity against FMEX and SKOV3 tumor cells. In some experiments, this cytotoxicity was greater than that in PBMC cultured in control medium with IL-2 and IL-12. Lower concentrations of IL-12 (1 U/mL) with IL-2 (100 U/mL) were as effective as, and often more effective than, higher doses of IL-12 with IL-2. Very low-dose IL-12 (0.01-0.03 U/mL) in combination with IL-2 also induced a range of cytotoxicities. Only the combination of IL-2 and IL-12 up-regulated expression of perforin mRNA in ascitic medium. CONCLUSIONS: The cytotoxicity responses of PBMC cultured in ascitic fluid in the presence of IL-2 and IL-12 are complex. Low-dose IL-2 and IL-12 can overcome the inhibitory property of ascitic fluid on LAK generation and can restore and enhance cytotoxic activity, possibly by reconstituting the expression of perforin. These findings may have therapeutic potential.

Ascites↗