PubMed Health⌕ Search

Biomedical subjects

J L Collins

Publications and source records attributed to J L Collins.

At least 19 recordsLinked to original sources
PubMed1992

Resistance to cytolysis by tumor necrosis factor alpha in malignant gynecological cell lines is associated with the expression of protein(s) that prevent the activation of phospholipase A2 by tumor necrosis factor alpha.

Although there are a limited number of cell lines that are sensitive to cytolysis by tumor necrosis factor alpha (TNF alpha), the vast majority are resistant. The analysis of TNF alpha-sensitive cells has shown that phospholipase A2 is activated by TNF alpha in these cells and that the activity of phospholipase A2 is required for their cytolysis. Many cell lines that are resistant to TNF alpha-mediated cytolysis are dependent on the maintenance of protein synthesis for their resistance. We have recently shown that this is also true for TNF alpha-resistant cell lines derived from cervical (ME-180 and SiHa) and ovarian (SK-OV-3 and OVCAR-3) carcinomas, in that they are sensitive to cytolysis by TNF alpha only in the presence of protein synthesis inhibitors. Here we show that the TNF alpha-mediated cytolysis of these resistant cell lines in the presence of the protein synthesis inhibitor emetine is similar to that of sensitive cells, in that cytolysis is inhibited by the inhibitors of phospholipase A2. The measurement of the release of radiolabeled material from cervical and ovarian carcinoma cell lines prelabeled with [3H]arachidonic acid showed that not only was phospholipase A2 required for the cytolysis of these cells by TNF alpha in the presence of protein synthesis inhibitors, but more importantly, phospholipase A2 was not activated by TNF alpha unless protein synthesis was inhibited. These results indicate that a protein synthesis-dependent resistance mechanism expressed by these cell lines blocks TNF alpha-mediated cytolysis by preventing the activation of phospholipase A2 by TNF alpha.

Animals↗
PubMed1992

Divergent effects of taxol on tumor necrosis factor-alpha-mediated cytolysis of ovarian carcinoma cells.

OBJECTIVE: Our objective was to study the combined effect of taxol and tumor necrosis factor-alpha on the cytolysis of human ovarian carcinoma cell lines, because taxol has been shown to be active against ovarian carcinoma and has also been shown to increase tumor necrosis factor-alpha release from macrophages. STUDY DESIGN: The combined effect of taxol and tumor necrosis factor-alpha on the cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780, which are sensitive to the cytolytic effect of tumor necrosis factor-alpha in the presence of inhibitors of protein synthesis, was investigated with a 24-hour chromium 51 release assay. RESULTS: At therapeutic concentrations taxol caused a significant increase in tumor necrosis factor-alpha-mediated cytolysis of Caov-3 and A2780 (p < or = 0.05). By contrast, taxol caused a decrease in the tumor necrosis factor-alpha-mediated cytolysis of SK-OV-3 and NIH:OVCAR-3 (p < or = 0.01). CONCLUSION: These results suggest that ovarian carcinomas have a heterogeneous response to the chemotherapeutic effect of taxol.

Carcinoma↗
PubMed1992

The effects of cyclosporin A on the lysis of ovarian cancer cells by cisplatin or adriamycin.

The major limitation to curative therapy for ovarian cancer is the development of drug resistance. Cyclosporin A (CsA), an immunosuppressive agent that has been used extensively in organ transplantation, also has been shown to decrease the resistance of cancer cells to some chemotherapeutic agents. Since cisplatin (CDDP) is the most common drug used for the treatment of ovarian cancer, we evaluated the potential of CsA to decrease resistance to CDDP in ovarian cancer cells selected for resistance to CDDP (A2780-CDDP). Although CsA significantly increased the sensitivity of A2780-CDDP cells to cytolysis by CDDP it did not increase CDDP sensitivity in the CDDP-sensitive parent cells (A2780), that is, CsA did not decrease basal resistance to CDDP. Both A2780-CDDP and A2780 are sensitive to cytolysis by Adriamycin (ADR). CsA significantly decreased the basal resistance of both cell lines to ADR. Interestingly, the effect of the protein synthesis inhibitors, emetine and cycloheximide, was similar to that of CsA, suggesting that CsA decreased selected resistance to CDDP and decreased basal resistance to ADR by affecting a protein synthesis-dependent resistance mechanism(s). In contrast to CsA and protein synthesis inhibitors, buthionine sulfoximine, an inhibitor of glutathione synthesis, decreased basal resistance of both cell lines to cytolysis by CDDP but not ADR, while verapamil, an inhibitor of P-glycoprotein, had no effect on cytolysis in either cell line. These results suggest that CsA may not decrease resistance to CDDP or ADR-mediated cytolysis by reducing glutathione or by inhibiting P-glycoprotein.

Antimetabolites, Antineoplastic↗
PubMed1992

Effects of radiation on TNF alpha-mediated cytolysis of cell lines derived from cervical carcinomas.

The effect of radiation, a primary mode of treatment for cervical malignancies, on the tumor necrosis alpha (TNF alpha)-mediated cytolysis of five cell lines derived from human cervical carcinoma cell lines (C-33 A, ME-180, HT-3, MS751, and SiHa) was analyzed. Results of this analysis showed that all of the cell lines were resistant to the cytolytic effects of TNF alpha. Although resistant when protein synthesis proceeds normally, ME-180, HT-3, MS751, and SiHa cells were sensitive to TNF alpha-mediated cytolysis in the presence of protein synthesis inhibitors. The cytolytic response of these cells to radiation was heterogeneous, with C-33 A cells being the most radiosensitive and SiHa cells being the least radiosensitive. The cell lines ME-180, MS751, and HT-3 were intermediate in their sensitivities to radiation. Because radiation is known to inhibit protein synthesis, the ability of radiation to enhance TNF alpha cytolytic activity was examined. The cell lines with intermediate sensitivities to radiation (ME-180, HT-3, and MS751) demonstrated statistically significant synergistic increases in cytolysis when exposed to TNF alpha in combination with radiation. Neither the radioresistant SiHa cell line nor the radiosensitive C-33 A cell line displayed increased cytolysis with increasing concentrations of TNF alpha at any dose of radiation. Possible mechanisms which may explain the synergy in ME-180, HT-3, and MS751 cells and lack of synergy in C-33 A and SiHa cells by TNF alpha and radiation are discussed.

Carcinoma, Squamous Cell↗
PubMed1991

Differences in the tumor necrosis factor-alpha-mediated lysis by fixed natural cytotoxic cells and fixed cytotoxic macrophages.

TNF-alpha has been shown to be associated with macrophage cell membranes in such a way as to retain cytolytic activity despite fixation of the macrophage effector cells with paraformaldehyde. In this paper we report that, similar to cytotoxic macrophages, natural cytotoxic (NC) cells also use cell-associated TNF to lyse sensitive target cells. However, in contrast to fixed cytotoxic macrophages, NC cells do not retain cytolytic activity after fixation with paraformaldehyde. Additionally, the cytolytic activity of paraformaldehyde-fixed NC cells is not increased by incubation with LPS or by incubation with rTNF before fixation. Western blot analysis indicates that, unlike macrophages, NC cells use a smaller (17 kDa) constitutively active form of TNF. These results indicate that, although both macrophages and NC cells use effector cell-associated TNF to mediate lysis of sensitive targets, the way in which TNF is associated with these two types of effector cells must be different.

Animals↗
PubMed1991

Inhibition of protein synthesis enhances the lytic effects of tumor necrosis factor alpha and interferon gamma in cell lines derived from gynecological malignancies.

Few clinical responses have occurred in preliminary studies using the cytokines tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma) in cancer patients. This may be related to the observation that many malignant cell lines are resistant to lysis by these cytokines in vitro. Resistance to lysis by TNF alpha or IFN gamma in many cells is controlled by a protein-synthesis-dependent mechanism, such that when protein synthesis is inhibited cells become sensitive to lysis by these cytokines. Because there is some evidence that TNF alpha and IFN gamma act through different lytic mechanisms and are opposed by different resistance mechanisms, we treated a panel of eight cell lines, five derived from human cervical carcinomas (ME-180, MS751, SiHa, HT-3, and C-33A) and three derived from ovarian carcinomas (Caov-3, SK-OV-3, and NIH: OVCAR-3) with both TNF alpha and IFN gamma to determine whether such combination treatment might maximize in vitro cell lysis. Our results showed that pretreatment with IFN gamma followed by exposure to TNF alpha in the presence of protein synthesis inhibitors increased lysis of seven of the eight cell lines above that seen with either TNF alpha or IFN gamma and inhibitors of protein synthesis. Only the cell line C-33A was resistant to lysis by TNF alpha and IFN gamma, when exposed to these agents both alone and in combination with protein synthesis inhibitors. Clinically, combining the cytokines TNF alpha and IFN gamma with protein synthesis inhibitors may maximize the in vivo lytic effects of these cytokines.

Cell Line↗
PubMed1991

Tumor necrosis factor alpha is elevated in the peritoneal fluid from women with ruptured ectopic pregnancies.

The purpose of this study was to determine whether exposure of the peritoneum to fetal tissue is associated with elevated tumor necrosis factor alpha (TNF alpha) levels in the peritoneal cavity. We measured TNF alpha levels in the peritoneal fluids and serum from women with ruptured ectopic, unruptured ectopic and intrauterine pregnancies, as well as nonpregnant women undergoing tubal ligation. The results showed that patients with ruptured ectopic pregnancies were more likely to have TNF alpha levels in the peritoneal fluid greater than 40 units/ml (68%), compared with women with unruptured ectopic or intrauterine pregnancies (21%) (p less than 0.05, Fisher exact test). No elevation of peritoneal fluid TNF alpha levels was found in nonpregnant patients. Because TNF alpha is primarily a product of activated macrophages, it is likely that elevated TNF alpha levels in the peritoneal fluid of women with ruptured ectopic pregnancies reflects activation of peritoneal macrophages.

Adolescent↗
PubMed1991

Serum CA-125 levels in women with ectopic and intrauterine pregnancies.

In women with ectopic pregnancies the extrauterine compartments are exposed to fetal tissue. Since such tissue is known to express CA-125, we measured serum levels of CA-125 in patients with ectopic pregnancies and compared them to those in patients with intrauterine pregnancies. A total of 44 pregnant women were included in the study; all were in the first trimester. Twenty-seven of them had ectopic pregnancies, and 17 had intrauterine ones. Our results show that women with ectopic pregnancies, ruptured or unruptured, were more likely to have elevated levels of serum CA-125 than were women who had intrauterine pregnancies.

Adult↗
PubMed1991

In vitro study of simultaneous infusion of incompatible drugs in multilumen catheters.

Multilumen catheters are commonly used to simultaneously administer incompatible drugs to critically ill patients. Though there are no known documented reports that this practice has been responsible for harmful events in patients, likewise there are no published data to verify the safety and efficacy of this practice. This study utilized an in vitro model flow system to examine the physicochemical phenomena that occur when two incompatible drugs (phenytoin and total parenteral nutrition) are simultaneously administered through multilumen catheters. Flow conditions and drug infusions in the venous model were designed to mimic the in vivo clinical situation to evaluate two central venous catheter types, a double- and a triple-lumen catheter. Video recordings were made of drug interactions, and assays of phenytoin concentration were performed on samples of the circulating fluid. White clouds of phenytoin precipitation were observed near the tip of the double-lumen catheter but not the triple-lumen catheter. Infusion through the double-lumen catheter resulted in an average of 6% loss of phenytoin to precipitate, which, on microscopic examination, appeared as spindle-shaped crystals 25 to 50 microns in length and 5 to 10 microns wide. In some cases, millimeter-size fragments of phenytoin precipitate were seen to dislodge from the tip of the double-lumen catheter. The adjacent orifices at the tip of the end hole of the double-lumen catheter appeared to permit interaction of the two effusing streams of the incompatible drugs, whereas the staggered orifices of the triple-lumen catheter reduce this interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization, Central Venous↗
PubMed1979

Anti-tumor potential of retinoic acid: stimulation of immune mediated effectors.

Data are presented on the effects of retinoic acid (RA) treatment on the in vivo growth of tumors in two mouse strains. Inhibition of tumor growth as a result of systemic RA injection was observed in three out of seven tumor models. Using adult thymectomized, lethally irradiated and fetal liver (A x TFL) reconstituted mice, we found that inhibition of tumor growth is not due to direct toxic effects of RA but rather appears to be the result of stimulation of thymus-dependent immune-mediated effectors to suppress tumor growth. Results suggest that only strongly immunogenic tumors are sensitive to in vivo retinoid inhibition.

Animals↗
PubMed1977

Characterization of an antigen from the myelogenous leukemia cell line K-562.

A protein was solubilized from the myelogenous leukemia cell line K-562 WITh 3 M KCl that specifically inhibited the antibody-dependent, complement-mediated cytolysis of 51Cr-labeled K-562 cells by a monkey antiserum to K-562. When the crude 3 M KCl extract uas fractionated with ammonium sulfate, an eightfold increase in specific activity (U inhibition/mg protein) resulted. This purified fraction migrated as a single protein band after polyacrylamide gel electrophoresis (PGE) with no detectable carbohydrate or lipid. The molecular weight of the denatured protein determined by sodium dodecyl sulfate-PGE was 77,000, similar to that of the native protein (80,000) determined by Sephadex exclusion chromatography. The protein was stable at pH 6-8, with an apparent isoelectric point between pH 5 and 6. In addition to being irreversibly denatured at pH 5 or less, it was unstable at osmolarities below 0.25 M (NaCl). It was denatured at temperatures of 56 degrees C or above. Normal human peripheral blood leukocytes were extracted similarly with 3 M KCl and fractionated with ammonium sulfate. Neither the crude preparation nor any fraction purified as described for the specific antigen inhibited the cytolytic assay, which indicated at least a quantitative lack of the protein on the surfaces of normal leukocytes.

Ammonium Sulfate↗
PubMed1977

A description of Walter Reed Army Medical Center's in-patient psychiatric service population 1973 to 1975.

A three-year evaluation of demographic and diagnostic patterns in a large Army psychiatric in-patient facility is described. Active duty personnel accounted for 83.6 percent of patient episodes. No simple catchment area could be defined for this facility. Active duty patient episodes tended to be with younger, junior enlisted men whose sicknesses were most frequently diagnosed as schizophrenia. The diseases of blacks were diagnosed as paranoid schizophrenia more frequently than in whites. Latent schizophrenia or undifferentiated schizophrenia were diagnosed more frequently in whites than in blacks. The illnesses of active duty female military personnel were more frequently diagnosed as neurotic than as schizophrenic. Of the patient episodes during the three-year period, 12.1 percent were about dependents. They were usually the wives of older, senior enlisted men or senior officers and they stayed an average of 12 days in the hospital. On the other hand, 4.3 percent of the patient episodes were about retired personnel. They came from Walter Reed Army Medical Center (WRAMC) as did their dependents, and the most frequent diagnosis was alcoholism. Their median stay was 15 days. Subsequent studies will attempt to further clarify these initial findings.

Adolescent↗