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Biomedical subjects

C Page

Publications and source records attributed to C Page.

At least 37 records · Page 2Linked to original sources
PubMed1998

Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis.

OBJECTIVE: To investigate the role of Bcl-xL in resistance to chemotherapy-induced apoptosis in ovarian carcinoma. METHODS: Two human ovarian carcinoma cell lines were used in this study: A2780 and SKOV3. A2780 cells were transfected with human Bcl-xL or control plasmid alone. Expression of Bcl-xL in single cell clones was analyzed by flow cytometry and protein expression was confirmed by Western blot. For in vitro chemotherapy-induced death assays, cisplatin and Taxol were used. The percentage of apoptotic cells was determined by nuclear propidium iodide staining followed by flow cytometric analysis. Human ascites samples were used to make tumor lysates which were then analyzed for expression of Bcl-xL protein by Western blot. RESULTS: A2780 cells express low levels of endogenous Bcl-xL while SKOV3 cells express high amounts as determined by Western blot. In addition, A2780 cells are sensitive to chemotherapy-induced cell death while SKOV3 cells are resistant. To determine if chemoresistance is mediated by expression of Bcl-xL, A2780 cells were transfected with Bcl-xL or control plasmid. Cells were incubated with either cisplatin or Taxol to induce apoptosis. Bcl-xL-expressing cells were highly resistant to cisplatin and Taxol compared with controls (P < 0.05). All samples of malignant ascites analyzed expressed high levels of Bcl-xL on Western blot. CONCLUSIONS: The results of these studies indicate that Bcl-xL is expressed in ovarian carcinoma, and in A2780 cells functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. This may have prognostic significance; previous studies have demonstrated that patients with breast cancer that overexpress Bcl-2 have low-grade, hormonally responsive tumors. In ovarian carcinoma, another Bcl-2 family member, Bcl-xL may be responsible for modulating resistance to chemotherapy-induced apoptosis.

Antineoplastic Agents↗
PubMed1998

Intrahepatic alpha beta-TcRintermediate LFA-1high T cells are stimulated during mouse hepatitis viral infection.

Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of thymic and extrathymic T cell subpopulation disorders induced during the viral hepatitis. To understand local hepatic immune responses, the phenotypes of resident hepatic lymphocytes were determined and compared that of splenic and thymic T cell subpopulations during the acute viral hepatitis induced by MHV3 in susceptible C57BL/6 mice. Single positive (SP) CD4+ or CD8+ cells strongly increased in the liver. A specific cell population, the double positive (CD4+ C8+) cells, normally present in liver and thymic cell preparations, decreased in C57BL/6 mice following the viral infection. alpha beta-TcRintermediate T cells shifted toward alpha beta-TcRhigh T cells in the liver and thymus of infected mice, but not in their spleen. The specific alpha beta-TcRint or high lymphocytes occurring in the liver of MHV3-infected mice expressed higher levels of leukocyte function antigen-1 (LFA-1) and Pgp-1 (CD44) activation markers, suggesting that they were either activated or antigen-experienced during the viral infection. No significant changes in T cell subpopulations were detected in the spleen. These observations suggest that MHV3 infection could induce an early in situ stimulation of resident hepatic T cells, despite a peripheral immunodeficiency in the thymus and spleen.

Animals↗
PubMed1998

The spirit in practice.

Health systems around the Western world are under increasing pressure to provide an effective service in the face of rising consumer demand, escalating costs for high-tech interventions and an ageing population. It is therefore judicious to look at ways in which we can continue to enhance the quality of life for all global inhabitants whilst diminishing the strain on the system. For both the carer and patient, this requires an adjustment in their interface, with an expanding educational component and an awakening of the Inner Healer of the patient. Inevitably this will call for a change in the emphasis during training both for orthodox and complementary practitioners and a deeper understanding of the six senses to access right brain awareness where the Inner Healer happily, but unhealthily, slumbers. Ultimately, the goal is to create a health service which truly serves the patient/client and the carer offering both to a greater state of total well-being.

Attitude of Health Personnel↗
PubMed1998

Inhibition of serum and transforming growth factor beta (TGF-beta1)-induced DNA synthesis in confluent airway smooth muscle by heparin.

1. Airway remodelling occurs in asthma and involves an increase in airway smooth muscle mass through cell proliferation and hypertrophy. Increased eosinophil density in the airways is a feature of asthma. Eosinophils exhibiting activation in the airways of asthmatics also exhibit increased expression of transforming growth factor beta (TGF-beta1). We have examined the capacity of TGF-beta1 and epidermal growth factor (EGF) to influence airway smooth muscle division and the effect of heparin on TGF-beta1. EGF and serum-induced smooth muscle DNA synthesis in confluent airway smooth muscle cells (ASMC) as an indication of entry into S phase preceding mitogenesis. 2. ASMC were obtained from cell populations growing out from explanted bovine trachealis muscle sections. Cell division was monitored in sparse plated cells by direct cell counting following nuclear staining. Cell DNA synthesis in confluent cells was monitored by uptake of [3H]-thymidine. 3. TGF-beta1 (100 microM) inhibited FBS (10%)-induced smooth muscle division in sparsely plated cells (40%). TGF-beta1 (100 pM) increased cell DNA synthesis (200%) in confluent cells in the presence of bovine serum albumin (BSA, 0.25%). EGF (0.7 nM) also increased airway smooth muscle DNA synthesis (69%) in the presence of BSA (0.25%). The facilitatory effect of TGF-beta1 was observed between 1-100 pM, while that of EGF was observed between 20 200 pM. 4. Heparin inhibited serum and TGF-beta1-induced DNA synthesis in confluent ASMC (55%), consistent with our previous observation of inhibition of division in sparsely populated ASMC (Kilfeather et al., 1995a). This action of heparin was observed between concentrations of 1-100 microg ml(-1). Heparin did not inhibit DNA synthesis in response to EGF. An anti-mitogenic effect of heparin was also observed against responses to combined exposure to TGF-beta1 and EGF. 5. There was a clear inhibitory effect of heparin in absolute terms against serum-induced division in cells plated at 10, 20 and 45 x 10(3) cells cm(-2). The inhibitory effect of heparin was also observed at a plating density of 45,000 cells cm(-2) when responses to serum were expressed as fold-stimulation of basal DNA synthesis. 6. These findings demonstrate a potential role of TGF-beta1, EGF and heparin-related molecules in regulation of airway smooth muscle division.

Animals↗
PubMed1998

The ability of a single serum progesterone value to identify abnormal pregnancies in patients with beta-human chorionic gonadotropin values less than 1,000 mIU/mL.

OBJECTIVE: To determine the test performance of a single serum progesterone value <5.0 ng/mL for detecting ectopic pregnancy or other abnormal pregnancies in symptomatic ED patients with beta-hCG levels <1,000 mIU/mL. METHODS: A prospective study of progesterone levels was performed in consecutive ED patients presenting to an urban teaching hospital from December 1995 to March 1997 with abdominal pain and/or vaginal bleeding, a positive qualitative beta-hCG, and a quantitative beta-hCG value <1,000 mIU/mL. Patients were excluded if they were status-post a dilatation and evacuation procedure, had insufficient serum to run the progesterone assays, or were lost to follow-up. Progesterone values were measured from the original beta-hCG sample. Final patient diagnosis was abstracted from hospital records. RESULTS: 127 patients met eligibility criteria. 39 patients were excluded, leaving a total of 88 enrolled patients. 76 patients with abnormal pregnancies were identified [9 ectopic pregnancies, 62 abnormal intrauterine pregnancies (IUPs), 5 abnormal IUPs vs ectopic pregnancies], 71 of whom had progesterone values <5.0 ng/mL [sensitivity 71/76 (94%), 95% CI 86-98%]. 12 patients with normal pregnancies were identified, all of whom had progesterone values > or =5.0 ng/mL [specificity 12/12 (100%), 95% CI 78-100%]. CONCLUSION: A single progesterone value <5.0 ng/mL has high sensitivity and specificity in detecting abnormal pregnancy in symptomatic ED patients with beta-hCG values <1,000 mIU/mL.

Biomarkers↗
PubMed1998

Pathway leadership: a mature framework for teams.

Shared Governance has been a successful organizational design for Central Baptist Hospital. We are addressing critical issues that impact our success, with involvement and facilitation of the employees who make up the organization. It will continue to change as our environment and system evolve. The movement from a traditional organizational structure and culture to one of embracing shared decision making gives leaders today an additional stressor. It is difficult to critically analyze your organization when you are faced daily with the external pressures of health care competition and the internal daily pressures of operations. It takes extra effort and introspection to recognize that you and your management team must undertake new and different behaviors to lead your organization into the next millennium. One thing is clear: If you do not create an environment that is flexible and able to accommodate change, your competitor will!

Communication↗
PubMed1997

Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.

BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.

Androstadienes↗
PubMed1997

Editorial

Explore the source record for details and available documents.

Journal Article↗
PubMed1997

Effects of dopamine and selective dopamine agonists upon platelet accumulation in the cerebral and pulmonary vasculature of the rabbit.

1. A selection of novel compounds were shown to exhibit dopaminergic activity in vitro. 2. 111Indium-labelled platelets were continuously monitored in the cerebral and pulmonary vasculature of anaesthetized rabbits. The effects of dopamine and selective dopamine receptor agonists on ADP and thrombin induced platelet accumulation were recorded. 3. Pretreatment with dopamine (2 mg kg(-1) min(-1), i.v.) significantly reduced ADP (20 microg kg(-1), i.v.) induced platelet accumulation in the pulmonary vasculature whereas lower doses had no effect. 4. Dopamine (100 microg kg(-1) min(-1) intra-carotid, i.c.) potentiated thrombin (90 u kg(-1), i.c.) induced platelet accumulation in the cerebral vasculature whereas higher doses (1-2 mg kg(-1) min[-1]) inhibited accumulation. 5. The selective dopamine receptor agonists tested did not significantly inhibit platelet accumulation induced by ADP or thrombin. Two of these selective agonists, at doses higher than the intended therapeutic doses, induced thrombocytopaenia and an associated increase in platelet accumulation in the lung in response to thrombin. 6. These results extend previous in vitro studies regarding the dual actions of dopamine upon platelets and show for the first time the effects of selective dopamine receptor agonists upon platelet aggregation in vivo.

2-Naphthylamine↗
PubMed1997

Mouse hepatitis viral infection induces an extrathymic differentiation of the specific intrahepatic alpha beta-TCRintermediate LFA-1high T-cell population.

Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent model for the study of thymic and extrathymic T-cell subpopulation disorders induced during viral hepatitis. It was recently reported that, in addition to the intrathymic T-cell differentiation pathway, an extrathymic differentiation pathway of alpha beta-T-cell receptor (TCR) T lymphocytes exists in the liver, and becomes important under pathological situations such as autoimmune diseases, malignancies or hepatic bacterial infections. In the present study, we compared the phenotypes of resident hepatic, splenic or thymic T-cell subpopulations during the acute viral hepatitis induced by HMV3 in susceptible C57BL/6 mice. The number of liver-resident mononuclear cells (MNC) increased during the viral infection, while cellularity decreased. Single positive (SP) CD4+ cells strongly increased in both the liver and thymus, while double positive (DP) (CD4+ CD8+) cells, present in the liver and thymus of mock-infected mice, decreased in C57BL/6 mice during the viral infection. A shift of alpha beta-TCRintermediate T cells toward alpha beta-TCRhigh was evidenced in the liver and thymus of infected mice, but not in the spleen. The few alpha beta-TCRint double negative (DN) (CD4-CD8-) cells also decreased following viral infection. alpha beta-TCRint or high lymphocytes expressing high levels of leucocyte function antigen-1 (LFA-1) increased in the liver of MHV3-infected mice. In addition, liver-resident T cells expressed strongly the CD44 (Pgp-1) activation marker, suggesting that they were either activated or antigen experienced during the viral infection. No significant change in T-cell subpopulations was detected in the spleen, suggesting that MHV3 infection could induce an early in situ differentiation of resident hepatic T cells rather than a recruitment of lymphocytes from peripheral lymphoid organs.

Animals↗
PubMed1996

AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay.

The genetic basis for didanosine (ddl) resistance in human immunodeficiency virus (HIV-1) has previously been shown to be commonly associated with a Leu to Val change at codon 74 in the HIV-1 RT gene. In this study sequential viral isolates were analyzed from five patients with prior zidovudine (AZT) use who received 6 to 16 months of ddl therapy. Following ddl therapy, viral isolates exhibited an increased AZT susceptibility and decreased ddl susceptibility. Sequence and nested PCR analysis of the HIV-1 RT gene revealed that two viral isolates contained the Leu to Val change at codon 74, and three other isolates with reduced susceptibility to ddl each contained changes at codons 65, 70, and 72. Site-directed mutagenesis was employed to insert specific mutations in RT gene of proviral clone pNL4-3. Analysis of virion-associated reverse transcriptase activity indicated that the Lys70Arg mutation resulted in an enzyme with 2- to 4-fold decreased susceptibility to ddATP. Statistical analysis of the inhibitory concentration for RT activity between pNL4-3 and mutant Lys70Arg viruses obtained in three independent RT inhibition assays was significant (P = 0.05) by student t test paired analysis. Drug susceptibility assays on the virus with Lys70Arg mutation showed a marginal decrease in susceptibility to ddl (1.5- to 2-fold) and about 4- to 6-fold decrease in susceptibility to AZT. Mutations Lys65Glu and Arg72Ser resulted in an impaired RT with greatly diminished functional RT activity. The AZT-associated Lys70Arg mutation results in an RT enzyme with decreased susceptibility to ddATP.

Base Sequence↗
PubMed1996

Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits.

1. Recent work has suggested that adenosine may be involved in asthma via the activation of A1 receptors. However, the role of the recently cloned A3 receptor in airways is largely unknown. In the present study, we have investigated the role of the A3 receptor in adenosine-induced bronchoconstriction in allergic rabbits. 2. Aerosol challenge of antigen (Ag) immunized rabbits with the adenosine precursor, adenosine 5'-monophosphate (AMP), resulted in a dose-dependent fall in dynamic compliance (Cdyn). The maximum fall in Cdyn in these rabbits was significantly greater than that in litter matched, sham immunized animals (P < 0.05). However, there was no significant difference in the maximum increase in airways resistance (Rt) between Ag and sham immunized rabbits (P > 0.05). 3. Aerosol challenge of Ag immunized rabbits with cyclopentyl-adenosine (CPA) (A1-receptor agonist) elicited a dose-dependent fall in Cdyn in Ag immunized rabbits and the maximum fall in Cdyn in these rabbits was significantly greater than that observed in sham immunized rabbits (P < 0.05). Similarly, CPA induced dose-dependent increases in R1 in Ag immunized rabbits whereas sham immunized rabbits failed to respond to CPA within the same dose range. The maximum increase in RL in Ag immunized rabbits was significantly greater than that of sham immunized rabbits (P < 0.05). 4. Aerosol challenge of either Ag or sham immunized rabbits with the A3 agonist aminophenylethyladenosine (APNEA) did not elicit dose-dependent changes in either RL or Cdyn. Moreover, there was no significant difference in the maximum response, measured by either parameter, between the two animal groups (P > 0.05). 5. These data provide further evidence for a role of the A1 receptor in the airways, but do not support a role for the A3 receptor in adenosine-induced bronchoconstriction in the allergic rabbit.

Adenosine↗
PubMed1996

Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics.

Theophylline has been shown by several investigators to attenuate the late asthmatic response (LAR) to inhaled allergen, suggesting that it has anti-inflammatory or immunomodulatory properties. We have, therefore, undertaken a double-blind, placebo-controlled study to examine the effects of low-dose theophylline on bronchoalveolar lavage (BAL) and blood T-lymphocyte profile and activation in asthmatics following antigen challenge and the development of a LAR. Peripheral blood and BAL samples were obtained from 17 subjects with mild atopic asthma before and after 6 weeks of treatment with either oral theophylline or placebo. The mean serum theophylline concentration achieved was 6.6 micrograms.mL-1, which is below the currently accepted therapeutic range. Following theophylline therapy, there was a significant decrease in the number of BAL lymphocytes compared to placebo. On flow cytometric analysis of BAL cells, a significant loss of CD3+ T-lymphocytes, comprising both CD4+ and CD8+ subsets, was demonstrated. Moreover, there was a decrease in the number of BAL CD4+ T-cells expressing the activation marker very late activation antigen-1 (VLA-1), and an apparent reduction in human leucocyte antigen-DR (HLA-DR). Correspondingly, this was accompanied in the blood by an elevation in the proportion of activated CD4+ T-lymphocytes, in particular those expressing HLA-DR. These findings provide further evidence that theophylline has an anti-inflammatory action in asthma.

Adult↗