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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 19 recordsLinked to original sources

Mortality among workers exposed to polychlorinated biphenyls.

On the basis of evidence from animal studies, polychlorinated biphenyls (PCBs) are considered potentially carcinogenic to humans. However, the results of studies in human populations exposed to PCBs have been inconsistent. The authors conducted a retrospective cohort analysis (1957-1986) comparing the mortality of 3,588 electrical capacitor manufacturing workers with known exposure to PCBs with age-, sex-, and calendar time-specific mortality rates for all whites in the United States. Proportional hazards modeling was also performed to examine the association between cumulative PCB exposure and site-specific cancer mortality. All-cause mortality (192 deaths observed, 283.3 expected) and total cancer mortality (54 deaths observed, 63.7 expected) were lower than expected. More deaths were observed than expected for malignant melanoma (8 observed, less than 2.0 expected) and cancer of the brain and nervous system (5 observed, 2.8 expected). The average estimated cumulative dose for the cases of brain cancer (22.9 units) was greater than for other workers (12.9 units), but the 95% confidence intervals around this difference were broad. The risk of malignant melanoma was not related to cumulative PCB exposure. These results provide some evidence of an association between employment at this plant and malignant melanoma and cancer of the brain. The possibility that the results are due to chance, bias, or confounding cannot be excluded.

Brain Neoplasms

Differential pp60c-src activity in well and poorly differentiated human colon carcinomas and cell lines.

The results presented in this report demonstrate increased pp60c-src kinase activity associated with moderate to well differentiated colon tumors, corroborating previous observations by other groups. Extension of this analysis to include a small number of poorly differentiated colon carcinomas revealed src kinase activity comparable to that observed in normal colonic mucosa, considerably less than that observed in moderate/well differentiated lesions. Correlations of src kinase activity with differentiation was confirmed within a panel of colon cell lines where increased activity, associated with moderate/well differentiated lines, was accompanied by increased expression of pp60c-src protein. Use of an antiphosphotyrosine antibody in immunoprecipitation revealed the presence of novel phosphotyrosyl cellular substrates in human colon cell lines displaying elevated pp60c-src kinase activity. These observations suggest a role for the src protooncogene in colonic differentiation pathways.

Cell Differentiation

Oncogene-mediated transformation of fetal rat colon in vitro.

Short-term maintenance of fetal rat colonic tissue in vitro has been demonstrated using a collagen matrix organ culture system. The introduction of single (v-myc, v-rasH, v-src) oncogenes or combinations of oncogenes (v-myc/rasH, v-myc/src) into normal colon mucosal elements was established using retroviral vectors, resulting in enhanced proliferation and migration of epithelial cells from the lumen of tissue implants. Expression of a single oncogene in normal colon epithelium did not result in the establishment of cell lines. In contrast, expression of cooperating oncogenic elements resulted in cell lines in greater than 80% of experiments, revealing different morphological characteristics dependent upon the oncogene combination used. Confirmation of the expression of viral transcripts was determined using Northern blot analysis and viral oncoprotein expression using Western blot analysis (p21) and an immunoprecipitation kinase assay (src). Expression of keratin filaments was lost following passaging of cell lines but could be induced by the myc/ras transformants by growth on Rat-1 feeder layers. This induction phenomenon was not observed with myc/src lines, and although these expressed high levels of sucrase isomaltase the epithelial origin of these cells is unclear. Karyotypic analysis performed on three myc/ras-transformed cell lines revealed a normal chromosome complement associated with transformation. In this report we describe a novel in vitro transformation system for normal rat colonic epithelium mediated by the introduction of oncogene elements using different retroviral vector constructs. The potential to generate cell lines representing different stages of neoplastic progression using relevant genetic components presents significant advantages for the study of cellular and molecular interactions underlying colon neoplastic progression.

Animals

Immunotherapy with RNA in cancer.

The effect of I-RNA therapy was studied in a B16 melanoma-C57BL/6J mouse system. After having primary B16 isografts excised, mice receiving syngeneic lymphocytes incubated in vitro with specific guinea pig B16 I-RNA showed significantly improved survival as compared to control mice receiving untreated lymphocytes. This therapeutic effect was tumor specific and RNase sensitive. Significant cytotoxicity against B16 cells in vitro was consistently observed with lymphocytes prepared from B16 I-RNA treated animals, whereas lymphocytes from control animals or those treated with RNase-degraded B16 I-RNA or 3LL I-RNA had no effect. Results suggest that the combination of surgery and immunotherapy with I-RNA may be useful in preventing tumor recurrence in certain patients with cancer.

Animals

Length of residence, life change and psychiatric morbidity in an Australian urban population.

A component of a large population study of a random sample of 750 Canberra residents is described, in which length of residence in Canberra is related to the quality and quantity of recent life experiences, and to indices of minor psychiatric morbidity (the General Health Questionnair and the Zung Depression Scale). Life event frequency, but neither measure of morbidity, distinguished between persons with different lengths of residence in Canberra. It can be suggested that a random sample, containing an under-representation of migrants and persons moving from rural to urban environments, in whom the transition in shifting place of residence would be expected to be greatest, is an inappropriate sample to test hypotheses concerning length of residence and psychiatric morbidity, Future studies should give due emphasis to the adequate inclusion of these groups of persons.

Australia

Circulating immune complexes in patients following clinically curative resection of colorectal cancer.

Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.

Adenocarcinoma

Transient carcinoembryonic antigen (CEA) elevations following resection of colorectal cancer: a limitation in the use of serial CEA levels as an indicator for second-look surgery.

In a previous study, other investigators recommended second-look surgery for colorectal cancer primarily on the basis of plasma carcinoembryonic antigen (CEA) rises and prepared a nomogram for ready recognition of these "significant" increases. We found 25 patients whose CEA levels met the recommended criteria for significance; however, in 9 of these patients the rises were transient. Eight had no clinical evidence of recurrent cancer and they might have had negative second-look surgery had this been done because of CEA rises alone. The use of the CEA nomogram merely eliminated laboratory variation as a cause of the CEA rise. It did not, however, rule out biologic causes of CEA rises, other than that of cancer, especially benign liver disease. We were unable to differentiate benign from malignant rises on the basis of CEA changes alone. Preoperative CEA values helped to separate the two rises. Transient rises usually began earlier. Malignant CEA rises were more likely to be exponential. The rate of rise alone did not discriminate between the two rises. Thus, although serial CEA levels were helpful in making the decision for reexploration, they did not substitute for complete clinical assessment.

Carcinoembryonic Antigen

Persistent sciatic artery and sciatic artery aneurysm: a hazard in hip surgery.

During a posterior approach to the hip joint great caution must be exercised in protecting a persistent sciatic artery. Inappropriate trauma could either cause peripheral embolization, propagation of mural clots, or rupture. Prior to ligation, arteriography is critical because, despite the presence of strong femoral or popliteal pulses, the persistent sciatic artery may be the main conduit to the lower extremity.

Aged

Impact of dramatized television entertainment on adult males.

The authors studied the effects of a week's viewing of five types of television programs, including those with predominantly helpful or hurtful content, on the aggressive mood and hurtful behavior of adult men. They found, within the population studied, a significant decrease in aggressive mood and lower levels of hurtful behavior in viewers of helpful programs as compared with a control group, as well as some evidence that emotional arousal in response to helpful programs is negatively correlated with aggressive mood.

Adult

Cell surface antigens in a rat colon cancer model: correlation with inhibition of tumor growth.

Chemically induced bowel tumors in Wistar/Furth (W/F) rats possess surface antigens analogous to those demonstrated in humans with colon carcinoma. To determine if these in vitro tumors markers have any in vivo significance, tumor isograft challenge experiments were performed. Groups of animals received three immunizing doses of 10(7) cells from chemically induced colon carcinomas NG-W1, DMH-W49, or DMH-W9 or small-bowel adenocarcinoma DMH-W7. Control rats were immunized with a noncross-reacting, virally induced mammary fibroadenoma A9-W1. Six weeks after immunization, all animals were challenged with 1 X 10(5) or 3 X 10(4) colon carcinoma NG-W1 cells. None of the NG-W1-immunized animals developed tumors after either NG-W1 challenge dose. In contrast to this strong protection by "private" tumor rejection antigen (TRA), protection by common or "tissue type specific" antigens was evident only if tumor volumes were measured. Twenty-two days after low-dose NG-W1 challenge, mean tumor volume (m) in animals immunized with colon tumor DMH-W9 (m=0.25 cu cm) and DMH-W49 (m=0.17 cu cm) were less (p less than 0.05) than in animals untreated (m=1.0 cu cm) or immunized with mammary fibroadenoma A9-W1 (m=0.9 cu cm). Embryonic antigens also may function as weak TRAs. NG-W1 challenge tumor volumes in fetal-gut-immunized (m=0.9 cu cm) and whole embryo-immunized animals (m=0.9 cu cm) were less (p less than 0.05) than in fetal-kidney-immunized (m=2.5 cu cm) or adult-colon-immunized animals (m=1.8 cu cm). Low-dose NG-W1 challenge tumor volumes were less (p less than 0.01) in multiparous females (m=0.3 cu cm) than in either untreated (m=1.2 cu cm) or age-matched virgins (m=1.4 cu cm). In vitro tumor markers in this model may serve an important function in vivo as TRAs.

Adenocarcinoma

Pulsatile buttock masses: gluteal and persistent sciatic artery aneurysms.

A case of persistent sciatic artery aneurysm in a 65-year-old woman was treated by exclusion and reconstruction with a saphenous vein graft. When cases such as this present as pulsatile buttock masses, arteriography is the most important diagnostic aide. It will indicate when the circulation must be reconstructed and when it is safe to simply ligate an aneurysm.

Aged

In vitro cell-mediated immune reactions of melanoma and colorectal carcinoma patients demonstrated by long-term 51chromium assays.

In a series of consecutive 51chromium (51Cr) assays, 21 melanoma and 14 colo-rectal carcinoma patients were tested for their in vitro cell-mediated immune reactions to melanoma, rectal adenocarcinoma, and normal fibroblast target cells. Blood lymphocytes (BL) from four individuals were included in each experiment. In 9/14 experiments the BL effects of 2 melanoma patients were compared to BL effects of 2 colorectal carcinoma patients. In two experiments, BL from 1 melanoma patient and 1 colorectal carcinoma patient were compared for cytotoxic effect with each other and with BL from 2 normal healthy donors, and in the remaining 3 experiments BL from 2 melanoma patients were compared with BL from 1 healthy donor and one patient bearing a tumor which was neither a melanoma nor a colorectal carcinoma. Eleven out of 14 experiments were performed in a criss-cross manner. Target cells in the first three tests of this series consisted of tumor cells and fibroblasts explanted from a single melanoma patient. In all of the remaining experiments, each BL population was tested for cytotoxicity against both a tumor-fibroblast target cell pair explanted from one of two melanoma patients and a tumor-fibroblast target cell pair explanted from a rectal adenocarcinoma patient. Out of 35 tumor patients, 27 (77%) demonstrated a selective cytotoxic effect on the tumor target cells compared to the corresponding fibroblasts, while 4 patients (11%) showed a selective effect on the fibroblasts, and 6/29 patients showed a selective effect on the other type of tumor cells compared to matching fibroblasts. In 8/11 experiments (including two repeat tests) tumor-specific BL effects were demonstrated in a criss-cross manner. BL separations and 51Cr tests were repeated in 11 of the 35 patients 2-4 weeks after their original tests. BL populations from these 11 patients reproduced their individual earlier effects, whether these effects showed specific, non-specific, or no cytotoxicity. In each assay, differences in sensitivity between fibroblasts and tumor target cells in matched pairs were analyzed by comparing the effects of BL from the two controls. No differences in target-cell sensitivity could be demonstrated.

Adenocarcinoma

A long-term 51chromium assay for in vitro cell-mediated tumor immunity. Correlation with simultaneously performed microplate assays.

In vitro assays of cell-mediated tumor immunity utilizing 51Chromium (51Cr) labelling of cultured adherent solid tumor cells were designed which allowed an effector cell/target cell incubation time of 48 h without overriding spontaneous 51Cr release. In a series of 16 consecutive experiments, blood lymphocytes from healthy human donors, from patients with tumors unrelated to the cultural tumor target cells, and from colon carcinoma and melanoma patients were tested for their cytotoxic effects on various target cell pairs, human colon carcinoma, melanoma, or skin fibroblasts. The same reagents were used in simultaneously performed microplate and 51Cr assays. Results obtained by visual counting of microplate tests and by 24-h assays of 51Cr release or 51Cr retention correlated in 20/25 effector-cell/target-cell combinations. In a series of six consecutive experiments, lymph-node cells from untreated Wistar/Furth rats, and rats bearing either chemically-induced colon carcinoma NG-W1 or polyoma virus-induced sarcoma P-W13 were tested for their cytotoxicity on syngeneic rat colon carcinoma and sarcoma target cells. Criss-cross type experiments were performed by microplate and 15Cr techniques done in parallel. Results obtained by visual counting of microplate tests and by 48 h assays of 51Cr release or 51Cr retention correlated in 15/18 effector-cell/target-cell combinations.

Adenocarcinoma

Tumor-associated and embryonic antigens in soluble fractions of a chemically-induced rat colon carcinoma.

Soluble intracytoplasmic protein fractions and solubilized tumor membrane preparations produced by 3 M KC1 or papain treatment were isolated from a 1,2 dimethylhydrazine-HC1 (DMH)-induced rat colon carcinoma, DHM-BU 1. Solubilized preparations were fractionated by DEAE cellulose and Sephadex G200 column Chromatography. Crude extracts and fractionated materials were tested for their ability to inhibit the cytotoxicyt of lymph-node cells (LNC) from rats bearing isografts of an N-methyl-N-nitro-N-nirosoguanidine (NG)-induced colon carcinoma, ng-W1...

Adenocarcinoma