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Biomedical subjects

P Cannon

Publications and source records attributed to P Cannon.

At least 37 records · Page 2Linked to original sources
PubMed1994

Epidermal growth factor receptor expression in breast cancer: association with response to endocrine therapy.

106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF-R, ER, Ki67, and c-erbB-2 product. All patients received assessable endocrine therapy following disease progression. Significant associations were observed between EGF-R and ER (inverse) and Ki67 (direct). No association was observed between EGF-R and the c-erbB-2 product. EGF-R expression was significantly associated with the loss of endocrine sensitivity in breast cancer. This was observed in both ER positive and negative disease. In ER positive breast cancers, EGF-R expression had no significant influence on the quality of tumour remissions. Further sub-classification of the ER/EGF-R data by Ki67 immunostaining showed that in ER+/EGF-R-disease, increasing proportions of Ki67 positive cells were associated with a decline in the numbers of women experiencing good quality tumour remissions. A similar trend was also observed in ER+/EGF-R+ tumours. The presence of c-erbB-2 protein product did not influence endocrine sensitivity in any of the ER/EGF-R sub-groups.

Biomarkers, Tumor↗
PubMed1994

Oestrogen-regulated genes in breast cancer: association of pLIV1 with lymph node involvement.

In order to isolate markers of oestrogen responsiveness in breast cancer, we have cloned a number of oestrogen-regulated genes. Two of these, pLIV1 and pLIV2 (pS2), have been shown to be predominantly expressed in oestrogen receptor (ER)+ tumours. In this study, we examined their expression in relation to various clinical and histopathological features of breast cancer, and showed that pLIV1, but not pS2, is significantly associated with lymph node involvement (P < 0.01), while pS2 is more frequently observed in premenopausal patients (P < 0.05). Subdivision of the pLIV1 data by ER and nodal status of the tumour identified a highly significant association between pLIV1 expression and lymph node involvement in ER-positive disease, with 15/24 (63%) ER+ pLIV1+ tumours showing nodal involvement. Conversely, 20/23 (87%) ER+ pLIV1- patients were lymph node-negative (P < 0.001). Subdivision of the pS2 data by ER status did not reach significance. The application of pLIV1 as a marker of lymph node involvement was further exemplified in small tumours (< < 2 cm), where 11/12 (92%) lymph node-positive patients expressed pLIV1, while 17/22 (77%) node-negative patients were pLIV1 negative (P < 0.001). Similarly, pLIV1 expression identified lymph node involvement in moderately differentiated tumours (P < 0.01), but was independent of vascular invasion. pLIV1 may, therefore, represent a candidate gene for metastatic spread in ER+ breast cancer.

Breast Neoplasms↗
PubMed1994

Inhibition of human immunodeficiency virus type 1 Tat-dependent activation of translation in Xenopus oocytes by the benzodiazepine Ro24-7429 requires trans-activation response element loop sequences.

Two benzodiazepine compounds, [7-chloro-5-(2-pyrryl)-3H-1,4 benzodiazapin-2-(H)-one] (Ro5-3335) and [7-chloro-5-(1H-pyrrol-2-yl)-3H-benzo[e] [1,4] diazepin-2-yl]- methylamine (Ro24-7429), inhibit human immunodeficiency virus type 1 (HIV-1) replication via a specific effect on the function of the transactivator protein, Tat. To gain further insight into the mechanism of action of these compounds, we have tested their effects in an alternative assay for Tat activation in Xenopus oocytes. In this system, translation of trans-activation response element (TAR)-containing RNA is activated by Tat. Both compounds specifically blocked activation of translation in a dose-dependent fashion, with Ro24-7429 showing the greater potency. In the Xenopus oocyte system, as in mammalian cells, mutation of the TAR loop sequences abolishes Tat action. However, it is possible to obtain TAR-specific, Tat-dependent activation of a target RNA with a mutation in the loop provided that this target is in large excess. This result has been interpreted as indicating that a negative factor has been titrated (M. Braddock, R. Powell, A.D. Blanchard, A.J. Kingsman, and S.M. Kingsman, FASEB J. 7:214-222, 1993). Interestingly Ro24-7429 was unable to inhibit the TAR-specific but loop sequence-independent mode of translational activation. This finding suggests that a specific loop-binding cellular factor may mediate the effects of this inhibitor of Tat action. Consistent with this notion, we could not detect any effect of Ro24-7429 on the efficiency of specific Tat binding to TAR in vitro.

Animals↗
PubMed1994

Analysis of Tat function in human immunodeficiency virus type 1-infected low-level-expression cell lines U1 and ACH-2.

The U1 and ACH-2 cell lines are subclones of human monocytic and T-lymphoid cells, respectively, persistently infected with human immunodeficiency virus type 1. These cell lines harbor the viral genome but produce only very low levels of viral progeny, which can be increased by stimulation with agents such as phorbol ester and cytokines. As such, they provide an in vitro model for human immunodeficiency virus type 1 latency. In order to examine the basis for their latent state, we have analyzed the activity of endogenous Tat protein in these cells and investigated the effect on viral replication of the addition of exogenous Tat protein. We find that U1 cells seem to have levels of Tat protein that are suboptimal for long terminal repeat (LTR) transcription, because transcription from a transfected LTR-chloramphenicol acetyltransferase plasmid can be enhanced by cotransfection of a Tat expression plasmid. Furthermore, viral replication can be stimulated in this cell line by incubation with purified Tat protein. In contrast, ACH-2 cells are not limited for LTR-chloramphenicol acetyltransferase transcription by endogenous levels of Tat, and virus production is not increased by the addition of exogenous Tat protein. By semiquantitative PCR analysis of viral RNA, we have demonstrated that Tat protein caused an increase in human immunodeficiency virus RNA expression in U1 cells but had no effect in ACH-2 cells. This suggests that a different mechanism underlies the latent state in U1 and ACH-2 cells.

Gene Products, tat↗
PubMed1994

Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones.

Matrix metalloproteinases are a highly regulated family of enzymes, that together can degrade most components of the extracellular matrix. These proteins are active in normal and pathological processes involving tissue remodeling; however, their sites of synthesis and specific roles are poorly understood. Using in situ hybridization, we determined cellular distributions of matrix metalloproteinases and tissue inhibitor of metalloproteinase-1, an inhibitor of matrix metalloproteinases, in endometrium during the reproductive cycle. The mRNAs for all the metalloproteinases were detected in menstrual endometrium, but with different tissue distributions. The mRNA for matrilysin was localized to epithelium, while the others were detected in stromal cells. Only the transcripts for the 72-kD gelatinase and tissue inhibitor of metalloproteinases-1 were detected throughout the cycle. Transcripts for stromelysin-2 and the 92-kD gelatinase were only detected in late secretory and menstrual endometrium, while those for matrilysin, the 72-kD gelatinase, and stromelysin-3 were also consistently detected in proliferative endometrium. These data indicate that matrix metalloproteinases are expressed in cell-type, tissue, and reproductive cycle-specific patterns, consistent with regulation by steroid hormones, and with specific roles in the complex tissue growth and remodeling processes occurring in the endometrium during the reproductive cycle.

Adult↗
PubMed1992

Reduced expression of AP27 protein, the product of a growth factor-repressible gene, is associated with diminished adipocyte differentiation.

We have recently characterized an adipocyte cDNA (clone 5) that is enhanced in expression by environmental and hormonal conditions favoring adipogenic differentiation. Moreover, certain agents including fibroblast growth factor and phorbol 12-myristate 13-acetate (but not epidermal growth factor) markedly inhibit clone 5 gene expression and prevent TA1 cell differentiation. These results led us to propose that a threshold level of the clone 5 gene product (AP27 protein) is required for triggering adipocyte differentiation. We have constructed vectors that direct the synthesis of clone 5 antisense RNA to reduce the levels of AP27 in adipogenic cell lines TA1 and 3T3-L1. We show here that when these cells express clone 5 antisense RNA, they fail to undergo morphological differentiation, whereas adipogenesis is unaffected in cells expressing antisense beta-actin or ferritin heavy-chain RNA. We further show that cells expressing clone 5 antisense RNA (but not the other antisense RNAs) are unable to induce the expression of characteristic "adipocyte-specific" mRNAs. The level of inhibition of differentiation by clone 5 antisense RNA correlates with decreased levels of AP27 protein. These results provide strong evidence that expression of AP27 is linked to adipogenic differentiation and that AP27 may be a component of an as-yet-uncharacterized signal-transduction pathway required for the triggering of adipocyte differentiation.

3T3 Cells↗
PubMed1983

Nifedipine in the treatment of hypertension.

Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p less than 0.05) and diastolic (p less than 0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (less than 160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.

Absorption↗
PubMed1980

Administering the contract.

Administering the collective bargaining contract is a challenging and important nursing administration responsibility. This article discusses the attitudes, skills, and strategies that the nursing administrator who manages a unionized professional staff can use to minimize employee grievances and foster a professional practice climate. Directors of nursing in nonunionized settings also can use these guidelines to maintain the union-free status of their departments.

Collective Bargaining↗
PubMed1979

Glucagon as a hypotonic agent in cholangiography.

The effects of Glucagon on 35 cholangiographic studies was examined. Relief of spasm at the choledochoduodenal sphincter resulted in consistently improved demonstration of this area. Diminished spasm-induced pain was also recorded. The use of intravenous Glucagon is recommended for cholangiographic studies where there is total biliary obstruction, or where there is unsatisfactory demonstration of the choledocho-duodenal area.

Aged↗