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L Faulkner

Publications and source records attributed to L Faulkner.

30 records · Page 2Linked to original sources

Regulation of c-fgr messenger RNA levels in U937 cells treated with different modulating agents.

The U937 cell line was used to investigate the induction of messenger RNA (mRNA) for the c-fgr mRNA tyrosine kinase proto-oncogene in cells of the monocyte-macrophage lineage. U937 cells were exposed to tumour necrosis factor-alpha (TNF-alpha), TNF-beta and transforming growth factor-alpha (TGF-alpha), alone and in combination with PMA and 1,25-dihydroxycholecalciferol (1,25-DHCC). TNF-alpha and TNF-beta, but not TGF-alpha, decreased the proliferation of U937 cells in a time- and dose-dependent manner, and both TNF-alpha and TNF-beta enhanced the response of U937 cells to PMA during the first 24 hr of treatment and to 1,25-DHCC over 72 hr. TNF-alpha induced a rapid increase in c-fgr mRNA levels within 4 hr, in contrast to slower induction by PMA and 1,25-DHCC. TNF-alpha and 1,25-DHCC together had an additive effect on c-fgr mRNA levels. In U937 cells exposed to PMA, c-fgr mRNA levels continued to increase over 72 hr. Levels of c-fgr mRNA induced by the various modulating agents did not correlate clearly with the changes in proliferation. Therefore, we suggest that although the c-fgr gene product may have a role in differentiation, the more significant role is likely to be in the fully differentiated macrophage.

Animals↗

Hypoxic fractions in xenografted human colon tumors.

We investigated the percentage of radiobiologically hypoxic cells within 11 different xenografted human colon tumors using an in vivo-in vitro excision assay technique. Tumors were excised at average volumes of 750 mm3, and it was found that hypoxic fractions varied from less than 1% (clone D) to over 80% (HCT-8). The geometric mean hypoxic percentage was 10.4% (95% confidence interval, 4.9 to 22.1%). Comparison of the percentage of hypoxia results from the xenografted human colon tumors to published data from xenografted melanomas suggests that transplanted colorectal tumors as a class contain significantly less hypoxia than do the melanomas.

Animals↗

Modification of the growth rates and hypoxic fractions of xenografted A431 tumors by sialoadenectomy or exogenously supplied epidermal growth factor.

We studied A431 epidermoid carcinomas xenografted into male nude mice either in the unperturbed state or after either surgical removal of the salivary glands or i.p. injection of exogenous epidermal growth factor (0.2 mg/kg daily for 7 days). The percentage of hypoxic cells in unperturbed tumors was 10.5% (95% confidence limits, 6.6-16.8%). In mice that received epidermal growth factor injections, hypoxic percentages decreased to 3.7% (1.7-7.8%), and tumor growth rates increased. In sialoadenectomized mice, hypoxic percentages increased to 35.2% (27.1-45.6%), and tumor growth rates decreased. These data indicate that the biology of solid tumors can be significantly modified by the host status.

Animals↗

The c-fgr proto-oncogene: expression in Epstein-Barr-virus-infected B lymphocytes and in cells of the myelomonocytic and granulocytic lineages.

The c-fgr proto-oncogene, which is a member of the c-src gene family, encodes the cytoplasmic tyrosine kinase p55c-fgr. Expression of the c-fgr gene is activated in human B lymphocytes following infection with Epstein-Barr virus, and the viral protein EBNA-2 is involved in mediating this effect. The only normal cells in which the c-fgr gene is known to be expressed are peripheral-blood granulocytes and monocytes, and tissue macrophages. In accordance with this, levels of c-fgr mRNA increase when the human promonocytic cell line U937 and the human myelomonocytic cell line HL60 are induced to differentiate. The enzyme activity and the expression pattern of p55c-fgr suggest that it is involved in regulating the responses of terminally differentiated granulocytes and monocytes to external stimuli, perhaps by controlling changes in cytoskeletal structure.

B-Lymphocytes↗

Proliferative T-cell response to glycoprotein B of the human herpes viruses: the influence of MHC and sequence of infection on the pattern of cross-reactivity.

Oligopeptides of the highly conserved herpes virus glycoprotein B (gB) were expressed from DNA fragments of the EBV gB (BALF4) and HSV-2 gB open reading frames as fusion proteins with the lambda CII protein and beta-galactosidase (GZ), respectively, in Escherichia coli. After immunopurification using anti-gB or anti-GZ affinity columns, the fusion proteins were used in vitro to stimulate human peripheral blood lymphocytes (PBL) or murine lymph node cells that have been primed with EBV, HSV-1, HSV-2, VZV or HCMV (all human herpes viruses) to proliferate. Results obtained in BALB/c mice indicate that different herpes viruses induce different levels of T-cell response to each other and to gB, over a range of type-specific and cross-reactive T-cell epitopes. There is a lack of correlation of immunogenicity and antigenicity in the generation of T-cell responses between some of the viruses. Major T-cell epitopes are located at the C terminal half of the gB molecule. The T-cell response to gB in healthy individuals seropositive for various combinations of the five herpes viruses differed markedly from individual to individual, even when they are seropositive to the same set of herpes viruses. However, two individuals with high proliferative T-cell response to VZV and sharing HLA A2, B7, DR2 and DQw1 are also good responders for cross-reactive gB/fragments and for virus antigen of all the five herpes viruses. Therefore the data obtained demonstrated that the MHC and the immune interaction arising from cross-reactive T-cell response evoked by other herpes viruses may determine the pathogenesis of a herpes virus infection.

Animals↗

The effect of endotoxin on peripheral blood lymphocytes in the rat.

We have studied the effects on peripheral blood lymphocytes of the administration to rats of a single dose of endotoxin. Lymphopenia occurred during the first hour, and persisted during 24 hours. Lymphocyte subpopulations were examined by flow cytometry. T-lymphocytes were relatively resistant to the initial effects of endotoxin, but there were no differences in the responses of cells identified as T-helper or T-suppressor/cytotoxic lymphocytes. The effects of endotoxin on peripheral blood lymphocytes is less extreme but appears more persistent than the effects on granulocytes.

Animals↗

Disseminating the principles of a community support program.

Oregon's Living in the Community (LINC) program for chronic patients succeeds because of effective collaboration between a state hospital and a community treatment and rehabilitation program. The authors trace the development of the LINC program from its beginning in the early 1970s as a progressive retraining project for Eastern Oregon State Hospital's "back ward" patients. They describe principles derived from the original project, such as the provision of training in the patient's natural environment, adoption of these principles into the Oregon community support program, and dissemination of LINC projects to other parts of the state. The authors conclude that such model programs can be transferred to urban and rural settings when supported by a statewide planning effort.

Chronic Disease↗

Acting on health.

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Breast Neoplasms↗