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Biomedical subjects

P Bromley

Publications and source records attributed to P Bromley.

At least 19 recordsLinked to original sources
PubMed2001

Complete inhibition of intimal hyperplasia by perivascular delivery of paclitaxel in balloon-injured rat carotid arteries.

PURPOSE: To determine whether perivascular delivery of paclitaxel prevents luminal narrowing after balloon injury by inhibiting intimal hyperplasia. MATERIALS AND METHODS: Immediately after balloon injury of the entire left common carotid artery, three slow-release formulations of paclitaxel or control formulations without drug were applied around a distal segment of the artery. The noninjured right carotid arteries were evaluated as a control. The animals were maintained for 14 and 28 days (n = 5 in each group at each time interval). Histology, immunohistochemistry, and morphometric analysis were performed. RESULTS: Injured nontreated arteries exhibited a pronounced intimal hyperplasia (0.185 +/- 0.01 mm2 at 14 days and 0.189 +/- 0.01 mm2 at 28 days) and a marked reduction in luminal area (44% at 14 days and 43% at 28 days). Medial area and the number of medial cells increased by 44% and 45%, respectively, at 14 days, and by 22% and 37%, respectively, at 28 days. Injured arteries treated with perivascular paclitaxel did not show any intimal hyperplasia, and luminal area was increased in five of six groups and was unchanged in one group. These arteries had an increased medial area but they had fewer medial cells than noninjured arteries. Injured arteries treated with control implants without paclitaxel exhibited intimal hyperplasia and luminal narrowing. CONCLUSION: Perivascular slow release of paclitaxel totally inhibits intimal hyperplasia and prevents luminal narrowing after balloon injury. Because of its efficacy, perivascular paclitaxel represents a possible approach for prevention of restenosis in humans.

Angiogenesis Inhibitors↗
PubMed1998

Giving something back.

The Taoist teachings of self-reflection, openness, and sharing of self illustrate the need for the seasoned professional to examine one's own practice and share with the greater professional community. Taoism incorporates interdependency and harmony for all systems and suggests that as individuals we rely on the well-being of the whole. Four specific methods provide meaningful ways to give back to the profession; networking, presenting, publishing, and professional association work. Implementing one or more of these methods promotes the profession's collegial spirit and facilitates one's own growth while giving to others.

Career Mobility↗
PubMed1997

A transgenic mouse model for the detection of cellular stress induced by toxic inorganic compounds.

Transgenic mice for genotoxicity testing have been developed, although no such models have been produced for the evaluation of toxic, nongenotoxic chemical compounds. We have developed a transgenic mouse model for the analysis of toxic inorganic compounds. We engineered a mouse lineage with the human growth hormone (hGH) gene under the control of the human hsp70 promoter, in which a plasma-detectable hGH response can be elicited by exposure to heat shock. In primary cell cultures from these mice, hGH release was observed following treatment with several toxic inorganics. Transgenic mice injected intraperitoneally with sodium arsenite, cadmium chloride, copper sulphate, or methylmercurium chloride showed significant hGH levels in plasma.

Animals↗
PubMed1997

Percutaneous gastrostomy in radiologic practice.

Long-term gastrostomy tubes have a well-accepted role in providing nutritional support. Traditionally they have been placed by surgeons and by endoscopists. In the last decade, radiologists have come to play a major role in the placement of gastrostomy and gastrojejunostomy devices, and can usually do so as effectively and at lesser expense. A technique for placement is outlined, with a discussion of patient selection and complications. A review of the literature is provided.

Contraindications↗
PubMed1994

Role of DNA fragmentation in T cell activation-induced apoptosis in vitro and in vivo.

Apoptotic cell death, characterized by DNA fragmentation and morphologic changes, has previously been shown to occur in immature thymocytes and some T cell hybridomas after activation. Like some other forms of apoptosis, DNA fragmentation during activation-induced cell death precedes the morphologic events. For apoptosis to proceed, activation of the cells must persist at least to the time of DNA fragmentation, before which the cells can remain viable if the activation signal is removed. Aurintricarboxylic acid (ATA) blocks activation-induced apoptotic cell death in a T cell hybridoma, and kinetic studies show that this inhibition occurs at or near the time of DNA fragmentation in the cells. Taken together with the ability of ATA to inhibit DNA fragmentation in isolated nuclei exposed to Ca2+ and Mg2+, these data strongly suggest that ATA prevents apoptosis via its ability to inhibit endogenous endonuclease activity, and, conversely, that this activity is required for this form of cell death. In vivo, ATA inhibits thymocyte depletion and DNA fragmentation induced by anti-CD3 Ab. Further, specific loss of V beta 8+ thymocytes after administration of staphylococcal enterotoxin B is blocked by administration of ATA. These observations support an essential role for DNA fragmentation as an irreversible step in activation-induced apoptosis in T cell hybridomas and during T cell development. This is contrasted with heat shock-induced cell death, in which inhibition of DNA fragmentation does not prevent loss of cell viability.

Animals↗
PubMed1994

Use of extracorporeal photochemotherapy in heart transplant recipients during acute rejection: a case study.

Despite the growing availability of improved immunosuppressive agents, acute and chronic rejection episodes remain a major complication in heart transplant recipients. The rejection of allografts is a normal part of the body's response to foreign antigens. The key to controlling this response is to administer a regimen of multiple immunosuppressive drugs. Evidence indicates that by adding extracorporeal photochemotherapy to a standard immunomodulatory regimen, the rejection process can be reversed without significantly increasing patient risk. In this case study we examine extracorporeal photochemotherapy and the care of patients receiving this therapy.

Graft Rejection↗
PubMed1993

DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death.

Cytotoxic T lymphocyte (CTL)-mediated lysis is accompanied by fragmentation of target cell DNA into an oligonucleosome ladder, a hallmark of apoptosis. Is this a fortuitous coincidence, or could CTL be inducing lysis by activation of the suicide signal? In this report we demonstrate that CTL-mediated target cell death can be blocked with the drug aurintricarboxylic acid (ATA). The abrogation of death correlates with the inhibition of DNA fragmentation. While ATA prevented DNA fragmentation, it failed to significantly alter protein, RNA, or DNA synthesis in the cell lines over the dose range used. In addition, there was no inhibition of cell-cell interaction or granule exocytosis during CTL-mediated killing. ATA also significantly inhibited the cytolysis and DNA fragmentation mediated by isolated cytolytic granules, as well as the granular protein fragmentin. We developed an assay in which target cells could be separated from CTL after binding and programming for lysis. Once they had received the "kiss of death," target cells could be rescued from lysis (as indicated by inhibition of DNA fragmentation and increased target cell viability) by treatment with ATA. These results suggest that ATA blocks target cell death by inhibition of DNA fragmentation, and further, that chromatin degradation is a cause rather than a result of cell death in CTL-mediated lysis.

Animals↗
PubMed1987

Heat-regulated expression of the hepatitis B virus surface antigen in the human Wish cell line.

The DNA fragment coding for the hepatitis B virus surface antigen (HBsAg) was placed under the control of a human 70 kDa heat-shock protein (hsp70) promotor sequence. This plasmid construct has been used in transfection experiments to establish a stable amnion cell line of human origin (Wish), expressing an HBsAg in a heat-regulated fashion. Post-translational modifications, such as assembly, glycosylation, secretion and production of both major and middle S proteins appear to function normally. In addition, production of HBsAg under various protocols of heat induction is described. After inoculation into nude mice, development of tumours has been observed at the site of injection. Tumour cells, dispersed by means of collagenase or trypsin treatment from excised tumours, and subsequently seeded into Petri dishes, were able to secrete the same quantities of HBsAg after heat induction as were cells of the original cell line.

Animals↗
PubMed1986

High-level, heat-regulated synthesis of proteins in eukaryotic cells.

Plasmids have been constructed in which promoters of 70-kDa heat-shock protein genes (hsp70) of human and Drosophila origin were linked to three different eukaryotic genes encoding human growth hormone (hGH), chicken lysozyme (cL) and a human influenza haemagglutinin (HA). Following transfection into widely divergent eukaryotic cells, the hybrid genes direct the transient, heat-regulated synthesis of the three proteins. hGH and cL are secreted into the medium. A human hsp70-hGH construct was used to establish stable mouse fibroblast lines that are capable of producing and secreting hGH at high levels following heat induction: hGH is secreted at a 500-1200-fold higher rate by heat-treated than by untreated cells.

Animals↗
PubMed1985

Isolation and functional analysis of a human 70,000-dalton heat shock protein gene segment.

A human 70-kDa heat shock protein (hsp70) gene segment has been isolated. The segment contains 3.15 kilobase pairs (kbp) of 5' nontranscribed sequence, an RNA leader of 119 bp, and a protein-coding region of 741 bp. The human protein sequence shows a high degree of homology to hsp70 sequences from other species. Expression experiments in Xenopus oocytes and mammalian cells indicate that a region that includes only 105 bp of 5' nontranscribed sequence contains all elements required for the efficient heat-controlled expression of the human gene. Two adjacent identical sequence elements, which are partly homologous to the Drosophila "heat shock consensus" sequence, are located 57 to 76 bp upstream from the capping site. Interestingly, the capping site itself is flanked by inverted repeat sequences.

Animals↗
PubMed1983

Structural similarities between corresponding heat-shock proteins from different eucaryotic cells.

Effects of heat treatments on chick embryo fibroblasts, Drosophila embryonic cells, and human lymphoblastoid cells have been compared. Cells from all three species synthesize large heat-shock proteins (hsps) with Mr = 70,000 and 84,000-85,000. Different small hsps with Mr between 22,000 and 27,000 are made at high rates in heat-treated chicken and Drosophila cells but could not be observed in human cells. The structural features of the large hsps from cells of the different organisms were compared by three methods of peptide mapping, namely the examination of tryptic digests by two-dimensional thin layer chromatography or by high pressure liquid chromatography and of incomplete V8 digests by polyacrylamide gel electrophoresis. The Mr = 84,000-85,000 polypeptides from all three organisms are closely related, the chicken and human polypeptides having many peptides in common. The relationship between the Mr = 70,000 polypeptides of the different organisms appears to be less close; possible explanations for this latter result are discussed. Rates of synthesis of total as well as poly(A)+ RNA are much lower in heat-treated than in untreated cells of all three organisms. Heat treatments induce dramatic changes in the shape of chick embryo fibroblasts as seen by microscopic examination. Human lymphoblastoid cells do not show changes in shape.

Animals↗