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Biomedical subjects

C G Taylor

Publications and source records attributed to C G Taylor.

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

The clinical relevance of chemosensitivity testing in ovarian cancer.

The aim of this study was to assess the role of in vitro chemosensitivity testing in ovarian cancer using the MTT assay. Cells were separated from solid biopsy or ascitic fluid samples from 73 patients with ovarian adenocarcinoma, FIGO stage III to IV, on presentation. A 48 h drug exposure was followed by the MTT assay to determine sensitivity. Patients were treated by conventional regimens containing platinum. There was a marked variation in sensitivity to the platinum drugs between individual patients. Clinical data were available for 37 patients. Eleven out of seventeen (65%) patients in the sensitive group had a complete response to therapy, compared with 3 out of 20 (15%) in the resistant group (p = 0.005). The overall survival rates were 36% for the sensitive group compared with 18% for the resistant group (p = 0.37). This study suggests that chemosensitivity testing in ovarian cancer may be effective in improving initial clinical response.

Adenocarcinoma↗
PubMed1998

Assessment of left ventricular diastolic function after single lung transplantation in patients with severe pulmonary hypertension.

OBJECTIVES: This study was designed to observe left ventricular filling by Doppler echocardiography before and after single lung transplantation in patients with severe pulmonary hypertension. BACKGROUND: Right ventricular pressure overload causes the deformation of the left ventricle by septal flattening toward its cavity, which may result in impaired left ventricular early filling. Recent studies have demonstrated the ability of single lung transplantation to restore right ventricular function in patients with severe pulmonary hypertension. However, changes in left ventricular filling after single lung transplantation have not been well studied. METHODS: We performed Doppler echocardiography in nine patients with severe pulmonary hypertension before, early (<3 months), and late (>1 year) after single lung transplantation. The study group consisted of eight female patients and one male patient with mean age of 32 years (range, 15 to 48 years). Six patients were diagnosed as having primary pulmonary hypertension and three as having secondary pulmonary hypertension. Nine age-matched normal subjects served as a control group. Doppler measurements included the following: transmitral flow early (E) and atrial (A) velocities, integrals (Ei and Ai), and left ventricular isovolumic relaxation time. The ratio of E/A and atrial filling fraction (Ai/Ei+Ai, AFF) were also determined. Left ventricular geometry was assessed from mid-short axis view with a circular shape factor (CSF). RESULTS: Early after lung transplantation, the left ventricular geometry became more circular with CSF (mean+/-SD) increasing from 0.63+/-0.09 to 0.88+/-0.05 (p<0.05). However, impaired early filling persisted in the patient group (E/A 0.7+/-0.1 vs preoperative 0.6+/-0.1, AFF 0.61+/-0.1 vs 0.64+/-0.1; both p=not significant). One year later, the left ventricular filling had returned to normal range with E/A 1.4+/-0.6 and AFF 0.35+/-0.1. CONCLUSIONS: This study observed that the impaired left ventricular early filling persisted shortly after single lung transplantation in patients with severe pulmonary hypertension, despite findings that left ventricular geometry was restored earlier after reversal of pulmonary hypertension. The abnormal filling pattern appeared to be resolved 1 year later. The findings suggest the impaired early filling may be caused by intrinsic left ventricular abnormalities other than ventricular interaction in these patients.

Adolescent↗
PubMed1997

Comparison of Zn and vitamin E for protection against hyperoxia-induced lung damage.

The objective of the present study was to demonstrate an antioxidant function for Zn in vivo by comparing the efficacy of Zn or Vitamin E without additional energy intake for protection of Zn-deficient (ZnDF) or energy-restricted (ER) rats from hyperoxia-induced lung damage. Zn (200 mumol ZnCl2/kg b.wt.) or Vitamin E (100 mg alpha-tocopherol/kg b.wt.) was injected IP before exposure to 85% oxygen or air for 5 d. During the exposure period, all injected ZnDF or ER rats were restricted to 5 g Zn-deficient or Zn-adequate diet/day, respectively, the amount of diet consumed by the untreated ZnDF or ER rats. We clearly demonstrated that injection of Zn without additional energy intake can protect ZnDF and ER rats from hyperoxia-induced lung damage assessed by the histopathological scoring system and magnetic resonance imaging (MRI). Vitamin E was not as effective as Zn in either ZnDF or ER rats for preventing hyperoxia-induced lung damage. Zn injection did not exert its antioxidant effect through increased lung CuZn-superoxide dismutase activity or metallothionein. This difference in the effectiveness of Vitamin E and Zn for hyperoxic protection in lung injury may be due to the specificity of antioxidant function, i.e., vitamin E inhibits oxidation of membrane lipids and Zn protects sulfhydryl groups of proteins.

Animals↗
PubMed1997

Splenocyte glutathione and CD3-mediated cell proliferation are reduced in mice fed a protein-deficient diet.

Protein-energy malnutrition (PEM) is associated with decreased host immune defense. Glutathione (GSH) status is reported to be decreased in PEM, and GSH is important for lymphocyte function. The objective of the present study was to investigate the effects of PEM and dietary repletion (RP) on GSH status in various tissues and splenocytes and on CD3-mediated calcium mobilization and cell proliferation of splenic T-lymphocytes. For the PEM model, mice were fed a 0.5% protein diet (LP group) for 4 or 6 wk, and control mice were fed a 15% protein diet (CP group). In the RP study, LP mice were fed the 15% protein diet for 3 d, 1 wk, 2 wk or 3 wk (RP groups). Glutathione concentrations were significantly lower in liver, lung, heart and spleen of LP mice compared with CP mice at 4 and 6 wk. Splenocytes from LP mice were significantly lower in number and had a lower intracellular GSH concentration, depressed CD3-stimulated T-lymphocyte proliferation in culture media without thiol supplementation (2-mercaptoethanol), and enhanced CD3-stimulated proliferation in thiol-supplemented culture media compared with splenocytes from CP mice. CD3-stimulated calcium mobilization was significantly lower in CD8+, but not CD4+, splenocytes from LP mice. Within 1 wk of dietary repletion, splenocyte GSH concentration was normal and splenocyte numbers were greater, and in vitro sensitivity of CD3-stimulated T-lymphocyte proliferation to thiol was lower, compared with LP mice. Glutathione status in vivo and thiol supplementation in vitro seem to modulate the signal transduction pathway for T-lymphocyte proliferation in mice with PEM.

Animals↗
PubMed1997

Radiation protection awareness in non-radiologists.

The outcome of teaching the core of knowledge to clinicians and the impact of the POPUMET regulations was assessed using an anonymous questionnaire. 82 of 120 (76%) of non-radiologists responded, of these 37% had attended a radiation protection course. Course attendance improved knowledge of the existence of the POPUMET regulations (p < 0.0001) and the ALARA principle. Course attendance made no difference to knowledge of the relative radiation dose of various radiological procedures. An underestimation of radiation dose was made by all responders (p < 0.001). The majority of responders were not aware that patients have no annual dose limit and the majority did not know the relative radiosensitivity of different organs. We have shown that despite the POPUMET regulations the majority of clinicians have not received adequate radiation protection teaching and that even if a course has been attended overall knowledge is still poor. We propose that formal compulsory teaching at undergraduate level may correct this in the future.

Clinical Competence↗
PubMed1996

An in vitro study of blast cell metabolism in acute myeloid leukaemia using the MTT assay.

We have utilized the MTT assay to measure the metabolic activity of cells from the bone marrow of 55 patients with acute myeloid leukaemia (AML), myelodysplastic syndrome (MDS) and non-clonal disease. Doubling dilutions of cells were exposed to MTT for 3-4 h. The mean optical density of the formazan produced by each cell dilution was plotted and the gradient of the line produced was calculated, higher gradients indicating more metabolically active cells. Results showed that the median activity of mononuclear cells from seven patients with non-clonal disease was 0.202 (range 0.175-0.253); blast cells from 27 patients with de novo AML had a median activity of 0.187 (range 0.079-0.345) and 13 patients with MDS a median of 0.155 (range 0.062-0.311). Seven assays on mononuclear cells from five patients in remission had a median activity of 0.203 (range 0.190-0.248), indicating no significant difference between these and normal patients. There was no correlation between the metabolic activity of cells when compared with their proliferative capacity, cell size and expression of P-glycoprotein. Following exposure of the AML patients' blast cells to the anthracyclines, cytosine arabinoside, 6-thioguanine and etoposide, cell survival was measured using the MTT assay. While there was no correlation between the in vitro sensitivity of these cells to the anthracyclines or etoposide, less metabolically active cells showed significantly greater sensitivity to 6-thioguanine. Conversely, the more active cells appeared to be more sensitive to cytosine arabinoside. Patients whose blasts cells showed higher metabolic activity appeared to achieve remission and had a longer mean survival time. Therefore, by using a simple technique we were able to establish that some patients were more likely to respond to certain cytotoxic regimes. Our preliminary study reflected the multifactorial nature of clinical response in AML and MDS, so providing further information on the relationship between cellular metabolic activity and treatment failure.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Aphidicolin markedly increases the platinum sensitivity of cells from primary ovarian tumours.

Enhanced DNA repair has been observed in cisplatin-resistant ovarian cancer cell lines. This resistance can be modulated, on co-incubation with aphidicolin in established cell lines and animal tumour models, by inhibiting DNA polymerases. We describe a study of the in vitro modulation effect of aphidicolin on cisplatin and carboplatin using fresh cells harvested from biopsy samples or ascitic fluids from 25 patients with ovarian adenocarcinoma. The MTT assay was used to measure cell survival after drug exposure. Aphidicolin (up to 30 microM) showed no cytotoxicity when tested alone. Forty-seven comparisons were made between drug with and without aphidicolin, and 37 (79%) cases demonstrated a significant increase in sensitivity to the platinum agents on co-incubation. Overall, there was a median 10-fold (range 1.64- to 58.5-fold) increase in sensitivity. When patients were grouped according to in vitro sensitivity to platinum, aphidicolin had a significantly greater effect in the "resistant' group, causing a median 13.5-fold increase in sensitivity compared with 2.4-fold in the "sensitive' group. Furthermore, a positive correlation between the LC50 for platinum and the corresponding fold increase in sensitivity suggests that aphidicolin overcomes platinum resistance in fresh cells from primary tumours. These results encourage the further development of this interesting compound.

Adenocarcinoma↗
PubMed1996

Identification and localisation of a type IV cytosolic phospholipase A2 in rat pancreatic beta-cells.

The liberation of arachidonic acid (AA), by phospholipase A2 (PLA2), is the rate-limiting step in a number of cell signalling pathways. In the pancreatic beta-cell, AA itself is thought to participate in the regulation of insulin secretion. Recently a Ca(2+)-sensitive, AA-selective cytosolic PLA2 (type IV cPLA2) has been isolated from the human monocyte U937 cell line. Although the DNA sequence of this enzyme implies a molecular weight of 85 kDa, the protein migrates with a molecular weight of 100-110 kDa on SDS-PAGE. In many cell types, cPLA2s which are reactive towards antibodies raised against the type IV cPLA2 have been shown to hydrolyse AA from membrane glycerophospholipids. Using a polyclonal antibody raised against a recombinant form of type IV cPLA2, we have detected an immunoreactive protein with a molecular weight of 93.5 kDa in rat islets of Langerhans. Furthermore, we have detected similar immunoreactive proteins in insulin-secreting beta-cell lines and have shown co-expression of type IV cPLA2 immunoreactivity and insulin immunoreactivity in rat pancreatic beta-cells. Under non-stimulatory conditions the 93.5 kDa immuno-reactive protein detected in rat islets of Langerhans was located predominantly in the cytosolic fraction. We have shown that immunoprecipitation of the rat immunoreactive protein from rat islet homogenates significantly decreases the total dithiothreitol/beta-mercaptoethanol-insensitive PLA2 activity by 56.4 +/- 7%. This provides further evidence that the immunoreactive rat protein is a type IV cPLA2 and is responsible for a large component of the PLA2 activity in rat islets of Langerhans. It is possible that, in the rat beta-cell, type IV cPLA2 couples the increase in intracellular Ca2+, brought about by insulin secretagogues, to the liberation of AA and the subsequent release of insulin.

Animals↗
PubMed1996

Diagnosis and classification of the acute leukemias: recent advances and controversial issues.

Although morphology and cytochemistry continue to be the mainstay of the diagnosis of acute leukemia (AL), new developments in immunophenotyping, cytogenetics, molecular biology, and in vitro assays have dramatically improved our understanding of this disease and enabled the identification of entities with distinct clinico-biologic features. Immunophenotyping is essential for diagnosing and subclassifying acute lymphoblastic leukemia (ALL) and is also very helpful in certain types of acute myeloid leukemias (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings are clinically relevant for diagnosis and prognosis. Nonrandom chromosomal abnormalities such as t(15;17)(q22;q12) or t(1;19)(q23;p13) have been so closely associated with distinct types of acute leukemias that their recognition can allow diagnosis independent of the other criteria. Molecular analysis is a powerful method in the assessment of the malignant potential, clonality, and classification of the ALs. It has become clear that in some leukemias a proportion of patients exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand apparently uniform chromosomal abnormalities such as the t(1;19), t(9;22), t(8;14), or t(15;17) may differ at the molecular level. In vitro assays can evaluate the growth pattern and cell-cycle kinetics of leukemic cells, as well as their sensitivity to therapeutic agents. All these data are relevant to the management of AL. Because the French-American-British (FAB) classification does not fully correlate with much of this new information, alternative classifications have been proposed. In this review we concentrate on recent diagnostic contributions resulting from advances in biotechnology and discuss some of the points that arouse controversy in the single classifications.

Acute Disease↗
PubMed1995

Contribution of immunophenotypic and genotypic analyses to the diagnosis of acute leukemia.

Diagnostic accuracy in acute leukemia (AL) can be improved if traditional morphology and cytochemistry are supplemented with immunophenotypic and genotypic analyses. This multiparameter approach is of crucial importance for the management of patients, as it enables the identification of leukemic syndromes with distinct biological features and response to treatment. Immunophenotyping using monoclonal antibodies has been universally accepted as a useful adjunct to morphological criteria. This technique is particularly valuable in diagnosing and subclassifying acute lymphoblastic leukemia and is also essential in certain types of acute myeloid leukemia (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings can be quite helpful in establishing the correct diagnosis and can add information of prognostic significance. A number of specific chromosomal abnormalities have been recognized that are very closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis, the polymerase chain reaction, and fluorescence in situ hybridization. With the extensive use of these techniques it has become apparent that a proportion of leukemias exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand, apparently uniform chromosomal abnormalities such as the t(1;19) (q23;p13), t(9;22) (q33;q11), t(8;14) (q24;q32), or t(15;17) (q21;q21) may differ at the molecular level. Data collected from these modern technologies have introduced a greater complexity, which needs to be taken into consideration to improve both the diagnostic precision and the reproducibility of current classifications.

Acute Disease↗
PubMed1995

Comparison of P-glycoprotein expression with in vitro drug sensitivity in fresh blast cells from acute myeloid leukaemia patients.

Anthracyclines and etoposide have been implicated in the multi-drug resistance phenotype. The mdr 1 gene encodes for the transmembrane protein P-glycoprotein. P-glycoprotein expression was measured in the fresh blast cells from 19 patients with acute myeloid leukemia using three monoclonal antibodies, C219, JSB-1 and MRK 16, and immunocytochemistry with the enzyme alkaline phosphatase as marker. Drug resistance can be identified in vitro using the predictive chemosensitivity test, the MTT (3-4,5-dimethylthiazol-2,5-diphenyl tetrazolium bromide) assay. In order to assess cell viability after drug exposure, this technique utilises the ability of cellular dehydrogenase enzymes to reduce the tetrazolium salt MTT to formazan. In vitro resistance to multi-drug resistance related cytotoxic agents was identified in the blast cells from these patients. This study showed no correlation between the results of the MTT assay and P-glycoprotein expression in this disease, suggesting either that more sensitive techniques are required to measure P-glycoprotein expression or that other drug resistance mechanisms may be involved.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Age-dependent injury in human umbilical vein endothelial cells: relationship to apoptosis and correlation with a lack of A20 expression.

BACKGROUND: It has recently been shown that human umbilical vein endothelial cells (HUVEC) become increasingly sensitive to growth factor deprivation, resulting in cell death, as a function of age in culture. The overall goal of the present study was to investigate the mechanism of lethal injury in these cells and compare the injury process to other known mechanisms of injury in the same cells. EXPERIMENTAL DESIGN: HUVEC were established in culture and maintained for four passages. Injury to first-passage cells and fourth-passage cells were examined for injury in the presence of agents that are known to confer resistance to apoptosis. Ultrastructural features of injury and DNA fragmentation patterns were assessed. Expression of factors that are known to be associated with resistance to apoptosis in other models were assessed. RESULTS: Fourth-passage HUVEC undergoing injury exhibited morphologic features characteristic of apoptosis and DNA fragmentation. Agents known to inhibit apoptotic cell injury in other models inhibited injury. A20 expression was correlated with resistance to injury in fourth-passage HUVEC, but there was no correlation between bcl-2 and bcl-x expression and resistance to injury. CONCLUSIONS: HUVEC injury resulting from growth factor deprivation increases as a function of age in vitro and appears to be a form of apoptosis. A20 expression may confer resistance to cell injury through this pathway.

Apoptosis↗
PubMed1994

Spontaneous injury to human umbilical vein endothelial cells increases during in vitro culture and is blocked by protein kinase activation.

BACKGROUND: The in vitro culture of human umbilical vein endothelial (Huve) cells alters sensitivity to cell injury. Late passage Huve cells in basal media have an increased susceptibility to spontaneous injury and this type of cell injury is blocked by phorbol myristate acetate (PMA). EXPERIMENTAL DESIGN: Protein kinase activation and alterations in free radical generation and defense were investigated as potential mechanisms for the increased spontaneous injury of late passage Huve cells in basal media and for the PMA-mediated protective response. RESULTS: The spontaneous injury of late passage Huve cells in basal media was blocked by PMA via a protein kinase-dependent mechanism. Huve cells cultured in vitro for several passages had increased basal particulate fraction protein kinase activity and increased activity in response to PMA treatment as compared with first passage cells. The spontaneous injury was not reduced by addition of free radical scavengers or iron chelators. The increased spontaneous injury in late passage Huve cells, and the protective effects of PMA treatment were not explained by alterations in the endogenous antioxidant defense system. PMA-mediated protection against spontaneous injury was blocked by staurosporine, a protein kinase inhibitor, but not by addition of various free radical scavengers or chelators. CONCLUSIONS: These data suggest that the cellular changes mediated by protein kinase are more important than free radical metabolism or antioxidant defense as an explanation for the increased spontaneous injury of late passage Huve cells in basal media and for the ability of PMA to block this type of spontaneous cell injury.

Alkaloids↗
PubMed1993

Tissue glutathione, nutrition, and oxidative stress.

Glutathione, a cysteine-containing tripeptide, is the most abundant nonprotein thiol in mammalian cells. Glutathione plays an important role in the detoxification of xenobiotic compounds and in the antioxidation of reactive oxygen species and free radicals. Because of its multiple functions in various tissues and its involvement in many diseases and malnutrition, a clear understanding of the interrelationships among tissue glutathione, nutrition, and oxidative stress is clinically relevant. The focus of this review is to discuss the regulation of tissue glutathione concentration by diet and nutritional status, and to apply this information to those diseases and malnutrition in which decreased tissue glutathione and increased oxidative stress are implicated. A potential strategy to rapidly restore glutathione for both antioxidant and immune defense systems before therapeutic treatment in malnourished patients is discussed.

Animal Nutritional Physiological Phenomena↗
PubMed1993

Heparin and pregnancy in women with a history of repeated miscarriages.

Many patients who experience recurrent spontaneous abortions (RSA) have high titered antibodies to trophoblast antigens and/or negatively charged phospholipids. Pregnancy success has been documented in some of these patients subsequent to heparin treatment. The effect of heparin on in vitro assays used to detect antibodies to phospholipids and trophoblast antigens has been investigated. We have found that complement-mediated detection of antibodies to trophoblast and lymphocyte antigens is inhibited by absorption of sera with solid-phase heparin. The data show that such inhibition involves an inhibitor and a heparin-sensitive regulator of the inhibitor. Heparin inhibits binding of antiphospholipid antibodies to phospholipids in solid-phase ELISA. The mechanism for this inhibition appears to involve an interaction between heparin and antibody to phospholipid. These findings reveal novel heparin-mediated reactions that bridge immunological and hematological interactions. The extent of heparin modulation of these antibody reactivities should be clarified in future clinical trials involving heparin treatment for RSA.

Abortion, Habitual↗