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Biomedical subjects

J Hurst

Publications and source records attributed to J Hurst.

At least 73 records · Page 4Linked to original sources

DNA methylation and the regulation of globin gene expression.

We have studied the effect of DNA methylation on human gamma-globin gene expression, using a novel in vitro DNA methylation technique. With this method we have methylated specific segments of the gamma-globin gene and its 5'-flanking region, which were cloned for this purpose in the bacteriophage vector M13mp8. The vitro methylated DNA was introduced into mouse L-cells by cotransfer using the herpes simplex virus thymidine kinase gene as a selective marker. Transformed cell lines were isolated to examine the inheritance of the segmental methylation pattern and its effect on the expression of the gamma-globin gene. Cells transformed with DNA methylated throughout the M13 vector and gamma-globin DNA sequences do not express the gamma-globin gene. Methyl-C residues in either the M13 DNA sequences or the gamma-globin structural gene have, however, no inhibitory effect on globin transcription. In contrast, methylation in the 5' region of the gamma-globin gene (from nucleotides -760 to +100) prevents transcription. These data indicate that DNA methylation in the 5' region of a gene might play a direct role in the regulation of gene expression.

5-Methylcytosine↗

Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes.

Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.

Animals↗

Production of fibronectin by normal and malignant human mammary epithelial cells.

The production and retention of fibronectin by primary cultures of cells derived from the human breast has been analyzed. Two examples of each of the following cell types were examined: (a) normal epithelium from milk; (b) metastatic breast cancer cells in pleural effusions; (c) fibroblasts; (d) tissue macrophages of milk. Cell-associated fibronectin could be detected by indirect immunofluorescent staining on normal and malignant mammary epithelium and on mammary fibroblasts, but not on milk macrophages. Immune precipitation followed by gel electrophoresis of 35S-labeled cell lysates and conditioned medium confirmed that fibronectin was indeed synthesized by both types of epithelial cells and by fibroblasts, but not by macrophages, and that much of the protein was released into the medium. Quantitative analysis with radioimmune assay of the fibronectin on cells and in media showed that both normal and malignant epithelial cells synthesized levels of protein comparable to that produced by fibroblasts, but only a small fraction (less than 10%) of the material synthesized was retained by the cells. Growth on collagen-coated plastic increased the percentage of fibronectin retained by normal and malignant epithelium but did not affect retention by fibroblasts.

Breast Neoplasms↗

Toxicology and pharmacology of some ruthenium compounds: Vascular smooth muscle relaxation by nitrosyl derivatives of ruthenium and iridium.

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55;dichlorobis(2,2'-dipyridyl)ruthenium(II), 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occurring in 4-7d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be due to the metal and not to its associated ligands. Only complexes having nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic agonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominus when these isolated muscles had been contracted by acetylcho line. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimally lethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.

Animals↗

Junctional intercellular communication pattern of cultured human breast cancer cells.

Junctional intercellular communication between several established human breast cancer cell lines and a variety of mammalian cells has been examined. All the cancer cell lines were found to be either noncommunicators or nonselective communicators. This contrasts with normal human mammary epithelium which shows selectivity in junctional communication. Loss of selectivity in junctional communication appears to be a general feature of cultured human breast cancer cells.

Animals↗

Childhood accidents--can they be prevented?

Accidents cause 10,000 children to attend Melbourne's Royal Children's Hospital Casualty Department each year. Most of these children sustain trivial injuries, which apart from some initial pain, cause no long term effects. About 1,000 of these children are admitted to hospital, many being discharged within a day or so with minimal upset to their way of life. However, some of these children suffer badly, and some die.

Accident Prevention↗

Fatal accidents to children: implications for prevention.

Effects to prevent childhood accidents should be directed at the causes of serious injury and death, rather than at the causes of the vast number of emergency department trivial injuries. This paper analyses fatal accidents, and suggests areas in which efforts at prevention may be effective. It emphasizes the importance of motor car accidents, and drowning accidents in childhood.

Accident Prevention↗

The role of the renal specialist nurse in prevention of renal failure.

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Diabetes Complications↗

Accreditation of post-basic nephrology courses within the EDTNA/ERCA.

This paper will outline the development of the EDTNA/ERCA accreditation programme for post-basic courses in nephrology. It will discuss results of the pilot project and relate the experiences of one school that has successfully gone through the accreditation process. The article will conclude with a discussion on more recent developments and evaluate the project in light of the original concepts.

Accreditation↗

A university accredited renal nursing course delivered by distance learning.

Continuous professional development (CPD) is limited in some regions of the UK and within Europe generally. This is compounded for all by limited resources for course fees and the lack of study leave granted away from the clinical area for full-time courses. This is set against recommendations from national and European governments and renal clinical guidelines concerning expectations of CPD and competency levels of renal nurses. In the past renal nurses have been trained in all areas of the speciality by local Schools of Nursing linked to renal units. However, since the formation of Trusts in 1990 education delivery has been ring-fenced and separated from the control of local hospitals by Schools of Nursing being incorporated into Institutes of Higher Education. That has led in some instances to a rationalising of post registration education delivery for some geographical areas. This paper will discuss the development and implementation of a distance learning renal care course taking into consideration the clinical, academic and educational requirements necessary for effective education and training at the post basic level.

Accreditation↗

Evaluating staff and student experiences of multidisciplinary continuous professional development via distance-learning.

Continuous professional development (CPD) in caring for people with kidney disease is limited in some regions of the UK and within Europe generally. This is compounded for all by limited resources for course fees and the lack of study leave granted away from the clinical area for full-time courses. This is set against recommendations from National and European governments, and renal clinical guidelines concerning expectations of CPD and clinical competency levels of renal nurses (1-4). In the past renal practitioners have been trained in all areas of the renal speciality by Schools of Nursing linked to renal units based in large teaching hospitals. However, more recent changes in the structure of Health Care provision have led in some instances to a rationalising of post registration education delivery.

Education, Distance↗