PubMed Health⌕ Search

Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 19 recordsLinked to original sources
PubMed2001

Mobile phones, heat shock proteins and cancer.

There are several reports which indicate that electromagnetic radiation (such as from mobile phones) at non-thermal levels may elicit a biological effect in target cells or tissues. Whether or not these biological effects lead to adverse health effects, including cancer, is unclear. To date there is limited scientific evidence of health issues, and no mechanism by which mobile phone radiation could influence cancer development. In this paper, we develop a theoretical mechanism by which radiofrequency radiation from mobile phones could induce cancer, via the chronic activation of the heat shock response. Upregulation of heat shock proteins (Hsps) is a normal defence response to a cellular stress. However, chronic expression of Hsps is known to induce or promote oncogenesis, metastasis and/or resistance to anticancer drugs. We propose that repeated exposure to mobile phone radiation acts as a repetitive stress leading to continuous expression of Hsps in exposed cells and tissues, which in turn affects their normal regulation, and cancer results. This hypothesis provides the possibility of a direct association between mobile phone use and cancer, and thus provides an important focus for future experimentation.

Animals↗
PubMed2000

Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension.

BACKGROUND: Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is thought to play a pathogenic role. METHODS AND RESULTS: An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (-20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (-26.2+/-12.8%, P<0.005) and mean arterial pressure (-19.8+/-14.4%, P<0.001). There was a slight increase in cardiac index (15+/-12%, P>0.05) and a dose-dependent rise in ET-1 but no significant change in other hemodynamic variables, gas exchange, or other vasoactive mediators. CONCLUSIONS: Intravenous bosentan is a potent but nonselective pulmonary vasodilator at the doses tested, even in patients resistant to inhaled nitric oxide. Transient increases in plasma ET-1 were observed, consistent with a blockade of endothelial ET(B) receptors. Systemic hypotension and other significant events during the study indicate that its intravenous use in patients with severe PHT may be limited. Implications for future trial design and studies of chronic oral treatment are discussed.

Adult↗
PubMed1998

Preclinical characterization of an anti-tat ribozyme for therapeutic application.

A hammerhead ribozyme retroviral construct, denoted RRz2, targeting the coding region of the human immunodeficiency virus type 1 (HIV-1) tat gene, has shown itself to be effective in a range of test systems. Inhibition of the replication of HIV-1 IIIB and primary drug-resistant strains in pooled transduced CEMT4 cells was consistently found to be more than 80% compared with the control-vector transduced cells, whereas a mutant RRz2 gave approximately 45% inhibition. A multiple HIV-1 passage assay showed the absence of emergence of mutations within the specific viral RNA ribozyme target sequences. This lack of generation of ribozyme "escape mutants" occurred despite the almost complete disappearance of a HIV-1 quasi-species in the testing virus. When RRz2 was tested in peripheral blood lymphocytes (PBLs) from HIV-1-infected patients, paired analysis showed that cell viability in the ribozyme-transduced HIV-1-infected PBLs was significantly higher than that in the vector-transduced cells. This difference in viability (vector versus RRz2) was not observed in PBLs from non-HIV-1-infected donors. Taken together, these results indicate that the transfer of an anti-HIV-1 ribozyme gene into human T lymphocytes could have major impact on viral replication and T cell viability in the HIV-1-infected individual.

Base Sequence↗
PubMed1998

Systemic sclerosis in DRw52-positive silica-exposed males: a case report.

The aims of this paper were to describe clinical and laboratory details of 4 siblings, of whom 2 have systemic sclerosis and to describe this family in the context of reported cases of familial systemic sclerosis. The proband and his affected male sibling share the tissue typing antigens: HLA11, B57, DR13, DRw52,- and DQ2,6. Both were concordant for gender, silica exposure, marital status, migration history and antinuclear factor status but discordant for systemic sclerosis subtype, age at disease onset and ENA status. One non-affected sibling had no disease despite concordance for gender, HLA status, silica exposure, marital status, and migration history.

Age Factors↗
PubMed1997

Australian Leukaemia Study Group myeloma II: a randomized trial of intensive combination chemotherapy with or without interferon in patients with myeloma.

The Australian Leukaemia Study Group has performed a randomized trial of interferon alpha-2A (Roferon-A) as a co-induction agent together with intensive combination chemotherapy and as maintenance following completion of 12 cycles of induction treatment. When used as a co-induction agent, interferon-alpha did not improve response rates, time-to-treatment failure, or overall survival. Patients who had interferon together with intensive combination therapy (PCAB: prednisone 60 mg/m2 days 1-5, cyclophosphamide 600 mg/m2 day 1, BCNU 30 mg/m2 day 1, doxorubicin 30 mg/m2 day 1, repeated every 28 d for a total of 12 cycles) had more leucocyte and granulocyte toxicity and received a lower dose intensive of cytotoxic drugs than those patients who received PCAB without interferon. There was a trend towards prolongation of plateau phase which did not reach significance. Interferon, however, did improve the survival of patients who achieved plateau; for those patients interferon was associated with a 33% decrease in the rate of death after adjusting for initial beta-2 microglobulin level.

Activities of Daily Living↗
PubMed1996

Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension. Their responses to inhaled NO predict their responses to other vasodilators, such as prostacyclin, and provide an estimate of the "fixed" component of their increased PVR. Some patients with limited cutaneous systemic sclerosis develop isolated pulmonary hypertension with a similar clinical course. Therefore, we have measured the acute hemodynamic response to inhaled NO in such patients. METHODS AND RESULTS: Seven patients were studied during inhalation of increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were collected on five patients. They demonstrated a selective, dose-dependent, and rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%). There was a nonsignificant increase in cardiac index but no change in mean arterial pressure or systemic vascular resistance. The mean right atrial pressure fell (27%), but there was no change in pulmonary artery occlusion pressure. Of the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease in total pulmonary resistance of at least 20%. CONCLUSIONS: Inhaled NO is an effective and selective pulmonary vasodilator in a significant number of patients with pulmonary hypertension associated with limited cutaneous systemic sclerosis. It may be useful in determining the potentially reversible contribution to the increased PVR and should be considered for patients with acute pulmonary vascular crisis.

Administration, Inhalation↗
PubMed1996

Bacillus Calmette-Guérin plus intravesical interferon alpha-2b in patients with superficial bladder cancer.

OBJECTIVES: Bacillus Calmette-Guérin (BCG) and interferon alpha-2b (IFN alpha 2b) have been used individually for the treatment of bladder cancer. We used a low dose of BCG combined with IFN alpha 2b to determine the safety and to assess the efficacy of this combination therapy. METHODS: A study of 12 patients with superficial bladder cancer evaluated the safety and efficacy of a combination of low-dose BCG and IFN alpha 2b, given weekly for 6 weeks. Three patients were assigned to each of four groups in which 60 mg of BCG was combined with 10, 30, 60, or 100 x 10(6) IU of IFN alpha 2b. RESULTS: The combination BCG/IFN alpha 2b therapy was well tolerated, with adverse effects being mild to moderate and resolved at the end of treatment. At 12 months post-treatment there has been no tumor progression. Two patients with previous multifocal transitional cell carcinoma have had solitary recurrences. One patient has had recurrent carcinoma in situ. CONCLUSIONS: This preliminary study found combination BCG/IFN alpha 2b induction therapy to be safe and well tolerated. These early results show a high response rate, but efficacy can only be determined with Phase II and III studies.

Adjuvants, Immunologic↗
PubMed1996

Both in vitro and in vivo irradiation are associated with induction of macrophage-derived fibroblast growth factors.

Fibrosis in the lung directly underlying the field of irradiation is an almost universal long term sequelae of thoracic irradiation. It is assumed to represent the consequence of direct damage to local tissues and/or vascular endothelium by ionizing radiation. This view, however, is not in keeping with our current understanding of fibrotic processes, which suggest that growth factors for fibroblasts (including platelet-derived growth factor (PDGF), insulin-like growth factor I (IGF-I)) and cytokines stimulating collagen synthesis (notably transforming growth factor-beta) are largely responsible for this process. Since a major source of these factors is the macrophage, present in large numbers within the lung, it appeared possible that radiation-induced fibrosis might be mediated by similar mechanisms. Therefore, a study was designed to determine, first, whether in vitro irradiation of mononuclear phagocytes could induce the release of growth factors for fibroblasts. Second, we wished to ascertain whether these same growth factors might also be secreted by bronchoalveolar cells from humans who had undergone in vivo thoracic irradiation. The results of this study indicate that irradiation of a number of different types of mononuclear phagocytes resulted in the dose-dependent synthesis and release of several growth factors for fibroblasts, including PDGF, tumour factor-alpha (TNF-alpha) and IGF-I. Further, cells obtained by bronchoalveolar lavage from patients undergoing thoracic radiation spontaneously released PDGF following irradiation. These findings strongly support the contention that synthesis and release of macrophage-derived growth factors for fibroblasts (particularly PDGF and IGF-I) occur after thoracic irradiation and play a significant role in the pathogenesis of irradiation-induced pulmonary fibrosis in humans.

Breast Neoplasms↗
PubMed1996

Primary infection with zidovudine-resistant human immunodeficiency virus type 1 does not adversely affect outcome at 1 year. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) variants with reduced in vitro sensitivity to zidovudine, conferred by specific mutations in the viral reverse transcriptase, emerge during prolonged therapy. Late-stage disease and declining CD4 cell count are associated with more rapid emergence of these resistant variants. Isolates of HIV-1 from seroconverters were screened for the zidovudine-resistance marker mutation at codon 215. HIV-1 with the altered genotype was detected in 5 (8.2%) of 61 patients soon after onset of symptomatic primary illness and from the sex partner of 1 patient. These transmitted resistant viruses were either replaced by strains susceptible to zidovudine within a few months of infection or persisted for up to 1 year in the absence of prolonged zidovudine therapy. The resistant genotype persisted in 3 of 5 seroconverters but in 2 patients had reverted to wild type at 48 and 52 weeks. Primary infection with zidovudine-resistant variants of HIV-1 was not associated with a more severe symptomatic primary illness or more rapid CD4 cell decline at 1 year after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Focal adhesion formation is associated with secretion of allergic mediators.

Adherence of cells to the extracellular matrix via focal adhesions is known to modulate many cellular functions. However, the role of focal adhesions in the regulation of secretion is unclear. To examine this we have used the RBL-2H3 rat mast cell line, in which we and others have observed cytoskeletal rearrangements and increased cell spreading during secretion. All activators of secretion examined, whether acting specifically through or bypassing the IgE-receptor, induced the assembly of focal adhesions, as defined by the localization of vinculin and talin. The extent of focal adhesion formation correlated with the extent of secretion and the time course of secretion also correlated with that of the assembly of focal adhesions. To examine the mechanism by which focal adhesion formation occurred, the protein kinase C inhibitor bisindolylmaleimide was used. Bisindolylmaleimide caused complete inhibition of both secretion and focal adhesion formation induced by antigen or the calcium ionophore A23187. Although PMA did not induce secretion, it induced focal adhesion assembly which was inhibited by bisindolylmaleimide. The inhibitor had no effect on secretion or focal adhesion formation induced by the ATP analogue, ATP gamma S in permeabilized cells, indicating ATP gamma S acts after the activation of protein kinase C in the secretory pathway. These data provide novel evidence that the formation of focal adhesions may have a role in the process of secretion from mast cells.

Adenosine Triphosphate↗
PubMed1995

Antiproliferative effects of bacillus Calmette-Guerin and interferon alpha 2b on human bladder cancer cells in vitro.

Direct inhibitory effects of bacillus Calmette-Guérin (BCG) and interferon alpha 2b (IFN alpha 2b) on six human bladder carcinoma cell lines, UCRU-BL-13, UCRU-BL-17, UCRU-BL-28, 5637, T24 and J82, were studied using an in vitro proliferation assay. Effects on proliferation following exposure to BCG or IFN alpha 2b were analysed by [3H]thymidine incorporation over 7 days. BCG had an antiproliferative effect on all bladder lines, while sensitivity to IFN alpha 2b varied greatly, being as remarkably low as 1 U/ml for some lines. The antiproliferative effect was greatest when cells were exposed continuously to either agent, but was still evident with a limited exposure. When clinical concentrations were simulated in vitro, BCG+IFN alpha 2b was more effective than BCG alone and as effective as a double BCG concentration. We conclude that, in addition to their immunomodulatory effects, BCG and IFN alpha 2b directly inhibit the proliferation of human bladder cancer cells, and often at extremely low concentrations.

Antineoplastic Agents↗
PubMed1995

Bacillus Calmette-Guerin (BCG) enhances monocyte- and lymphocyte-mediated bladder tumour cell killing.

A cytotoxicity assay was used to study the action of bacillus Calmette-Guerin (BCG) and cytokines on four human bladder cancer cell lines. Monocytes and lymphocytes from peripheral blood were incubated with or without BCG or cytokines for 24 h, after which [3H]thymidine-labelled target cells were added and the 72 h percentage specific release determined. BCG had a direct cytotoxic effect against tumour cells and significantly enhanced monocyte/macrophage and enhanced lymphocyte cytotoxicity against one cell line (UCRU-BL-17). Supernatants (SNs) from BCG-activated monocytes/macrophages and lymphocytes increased the percentage specific release of [3H]thymidine from UCRU-BL-17 cells. Interferon alpha (IFN-alpha) and interleukin 2 (IL-2) were cytotoxic towards UCRU-BL-17. No synergy occurred between BCG and cytokines at the concentrations tested. The results suggest that BCG is superior to IFN-alpha, interferon gamma (IFN-gamma) and IL-2 in enhancing cell-mediated cytotoxicity.

Carcinoma, Transitional Cell↗