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Biomedical subjects

K Cullen

Publications and source records attributed to K Cullen.

At least 19 recordsLinked to original sources
PubMed2001

The drug resistance proteins, multidrug resistance-associated protein and P-glycoprotein, do not confer resistance to Fas-induced cell death.

BACKGROUND: Multidrug resistance (MDR) is mediated by the drug resistance proteins, the multidrug resistance-associated protein (MRP) and P-glycoprotein, both of which confer resistance by the active efflux of chemotherapeutic drugs from the cell. Reduced Fas (CD95/APO-1) expression and resistance to Fas-mediated apoptosis have also been correlated with P-glycoprotein-mediated MDR. METHODS: We investigated cell surface Fas expression (using anti-Fas monoclonal antibody DX2.1) in a series of MRP-expressing drug-resistant leukemia sublines, and P-glycoprotein-expressing leukemia sublines, and their susceptibility to apoptosis induced by anti-Fas treatment (CH-11 monoclonal antibody). Caspase-3 activation was detected by Western blot and apoptosis was determined by flow cytometry with 7-aminoactinomycin D (7-AAD) staining of cells. RESULTS: Fas expression was not reduced in either the MRP- or P-glycoprotein-expressing drug-resistant cell lines, although expression was reduced by 15% in one low-level drug-resistant subline. Expression of MRP or P-glycoprotein did not confer resistance to caspase-3 activation or to anti-Fas-induced cell death. CONCLUSIONS: MDR mediated by the drug transport proteins MRP and P-glycoprotein does not correlate with resistance to Fas-mediated cell death or resistance to caspase-3 activation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Family and child-care provider influences on preschool children's fruit, juice, and vegetable consumption.

Children's intakes of fruit, juice, and vegetables (FJV) do not meet the recommended minimum of five daily servings, placing them at increased risk for development of cancer and other diseases. Because children's food preferences and practices are initiated early in life (e.g., 2-5 years of age), early dietary intervention programs may have immediate nutritional benefit, as well as reduce chronic disease risk when learned healthful habits and preferences are carried into adulthood. Families and child-care settings are important social environments within which food-related behaviors among young children are developed. FJV preferences, the primary predictor of FJV consumption in children, are influenced by availability, variety, and repeated exposure. Caregivers (parents and child-care providers) can influence children's eating practices by controlling availability and accessibility of foods, meal structure, food modeling, food socialization practices, and food-related parenting style. Much remains to be learned about how these influences and practices affect the development of FJV preferences and consumption early in life.

Beverages↗
PubMed2001

Molecular biomarkers in HNSCC: prognostic and therapeutic implications.

The prognosis of squamous cell carcinoma of head and neck (HNSCC) is influenced by many factors, such as performance status, TNM staging and pathological grading of differentiation. However, these factors are not sufficient for predicting outcome. Therefore, recent research has focused on the identification of molecular biomarkers. These markers help to stage patients in more meaningful prognostic groups and identify high-risk patients who may benefit from a more aggressive treatment approach. They also identify patients who are resistant to radiotherapy or chemotherapy, potentially avoiding the morbidity and cost of ineffective therapies. They can also identify patients with a high risk of recurrence who may benefit from chemoprevention. Finally, these markers may serve as targets for novel therapies, which would eventually change the outcome of HNSCC.

Biomarkers, Tumor↗
PubMed2001

Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis.

BACKGROUND: Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors. METHODS: To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients. RESULTS: IGF-1, ICGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. CONCLUSIONS: These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.

Adult↗
PubMed2001

Use of Indermil tissue adhesive for closure of superficial skin lacerations in children.

BACKGROUND: The aim of this study was to assess the use of tissue adhesive for paediatric wound closure in a minor injuries environment. METHODS: A n-butyl 2-cyanoacrylate adhesive formulation was used for the closure of traumatic skin lacerations in 56 children. RESULTS: Tissue adhesive succeeded in approximating skin margins in all cases. No episodes of wound dehiscence were experienced. There were no incidences of wound infection. CONCLUSIONS: This study indicates that this form of tissue adhesive can safely and effectively be utilised for traumatic superficial skin closure in children.

Adolescent↗
PubMed1999

Ethnic differences in cancer risk behaviors through the transition out of high school.

Differences were assessed by ethnic group in the performance of cancer risk related lifestyle behaviors through the transition out of high school. Data were obtained from a nationally representative probability sample survey, the 1992 National Health Interview Survey-Youth Risk Behavior Survey. A cross-sectional sub-sample included adolescents with an age range from high school freshmen to young adults within four years after high school. Self reported indicators of diet, physical activity, cigarette smoking, smokeless tobacco use, alcohol use, and sexual practices were the primary dependent measures. Cancer risk increased at the transition out of high school through changes in cancer related behaviors. Hispanic-American males experienced somewhat higher risks after the transition for chewing tobacco and snuff. African Americans experienced somewhat higher risks after the transition for physical activity, chewing tobacco, and number of sexual partners. Further research needs to verify these findings with longitudinal designs, assessment of tracking of behaviors through the transition, and of the ecological, social and psychosocial correlates that may explain why these changes occurred.

Adolescent↗
PubMed1999

Enhancing the quality of home health care.

A strong partnership between clinical practice and nursing education is essential to innovative home health care services. Nevertheless, these two components have not always worked in close association for mutual benefit--bringing the two together has been a continuing challenge. Recently, such an alliance was achieved in Edmonton, Alberta, brought on by necessity and triggered by rapid and substantial changes in both home health care and nursing educational environments.

Alberta↗
PubMed1996

Gamma knife pallidotomy in advanced Parkinson's disease.

Posteroventral pallidotomy as a treatment for Parkinson's disease (PD) has been the subject of increasing interest. We treated 4 nondemented patients with advanced PD, 2 with severe bradykinesia and a declining response to medication, and 2 with marked clinical fluctuations. All patients received 180 Gy delivered in one sitting to the right posteroventral pallidum site, used by Laitinen and colleagues, adjusted as needed, to avoid the optic tract. Only 1 patient changed significantly. Dyskinesia completely resolved on the side contralateral to the lesion in this patient. This same patient also became transiently demented and psychotic. The other 3 patients suffered no clearly identifiable beneficial or harmful effects. Follow-up magnetic resonance imaging scans of the brain at 1 year revealed lesions exactly where targeted although of unequal sizes. Our negative experience forces us to conclude that either larger volumes of tissue must be ablated, that physiologic monitoring is required for placing a lesion, that our subjects were poor candidates for the procedure, or that surgical ablation and radiation cause tissue damage of different types with different results.

Aged↗
PubMed1996

The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer.

Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen receptor positive tumor which was originally derived from a T1N0M0 invasive ductal cancer and has been carried as a serially transplanted xenograft in nude mice. T61 is a hormone sensitive tumor whose growth is suppressed by both estrogen and tamoxifen, in contrast to other estrogen receptor positive tumors such as MCF-7 which are stimulated by estrogen. Molecular studies have demonstrated that T61 expresses easily detectable levels of mRNA for a number of peptide growth factors, including transforming growth factor alpha (TGF-alpha) and insulin-like growth factors I and II (IGF-I and IGF-II), but not transforming growth factor beta-I (TGF-beta1). Of these, IGF-II is the only peptide whose expression is altered by endocrine therapy. Treatment of T61-bearing nude mice with physiologic doses of estrogen is accompanied by loss of IGF-II mRNA expression within 24 hours, and rapid regression of tumor. T61 tumor growth is also inhibited in animals treated with a monoclonal antibody which blocks binding of ligand to the IGF-I receptor, which mediates the mitogenic signal of bound IGF-II through autophosphorylation of its intracellular tyrosine kinase domain. These results demonstrate the utility of the T61 model in the study of the molecular mechanism of estrogen therapy in breast cancer, and suggest that in this system, modulation of a specific growth factor (IGF-II) by endocrine therapy can have profound effects on tumor growth.

Animals↗
PubMed1994

Transfected MCF-7 cells as a model for breast-cancer progression.

The MCF-7 human breast carcinoma cell line has been used as a recipient for eukaryotic plasmid expression vectors to determine the effects of growth factor and growth factor receptor overexpression on the estrogen-dependent, antiestrogen sensitive and poorly metastatic phenotypes exhibited by this line. Overexpression of some members of the erbB family of ligands and receptors were found to have some effects on these phenotypes. However, only when two members of the fibroblast growth factor family, FGF-1 and FGF-4, were overexpressed was progressive in vivo growth observed is either ovariectomized nude mice without estrogen supplementation or in mice that received tamoxifen treatment. FGF transfected cells also exhibited an increased ability to form micrometastases. The implications of these results with regard to the possible role of the paracrine and autocrine effects of angiogenic growth factor production in breast cancer progression are discussed.

Adenocarcinoma↗
PubMed1994

Practical considerations for the use of the optical disector in estimating neuronal number.

The aim of this study was to establish methodological variability in the estimation of the total number of neurones using the optical disector. Variations in the 3 dimensions of the disector probe were analysed under uniform sampling conditions in 50-microns-thick frozen sections of the human mediodorsal thalamic nucleus. There was no significant difference between the estimated neuronal number using samples of variable height (fractionator vs. non-fractionator sampling). In addition, different methods of volume calculation (individual sample vs. an average) did not significantly change the estimated total neuronal number. Large variations in the estimated total neuronal number occurred when the x and y dimensions of the disector probe were altered. In this study, accurate and reproducible estimates were achieved when the disector probe was large enough to have a probability of sampling at least 2 cells per frame. We conclude that the variables in the x-y plane (the disector frame size as well as the sample interval) significantly contribute to differences in the estimated total neuronal number. Several practical measurements to estimate this probability and enhance experimental design are discussed.

Cell Count↗
PubMed1994

Neuropathological correlates of memory dysfunction in the Wernicke-Korsakoff syndrome.

The Wernicke-Korsakoff syndrome is a neuropathological term which encompasses two clinical syndromes in thiamine-deficient alcoholics, Wernicke's encephalopathy and Korsakoff's psychosis. Wernicke's encephalopathy is characterised by eye and gait disorders and mental confusion, and can lead to the profound and permanent amnesia known as Korsakoff's psychosis. Despite this specific difference, both conditions appear to have identical neuropathology with haemorrhages and other lesions around the ventricular system. The memory deficit has been attributed to a number of brain lesions, including a recent suggestion that brain pathways utilising particular neurotransmitters are specifically damaged. To examine this, the number of chemically identified neurons in particular brain regions was quantified in patients with Wernicke's encephalopathy alone or in combination with Korsakoff's psychosis and compared with age- and sex-matched controls. Noradrenaline, a neurotransmitter thought to be involved in the process of selective attention, is localised in pathways projecting to the cortex. Our patients with either Wernicke's encephalopathy or additional Korsakoff's psychosis do not differ from controls in the distribution and number of these cells. Serotonin is another neurotransmitter that has been linked with alcohol dependency. Both patient groups have a profound loss of serotonin-containing neurons compared with controls. The loss of forebrain neurons containing acetylcholine in patients with Alzheimer's disease has implicated this neurotransmitter in the maintenance of memory functions. There was a large variation in the number of these forebrain neurons in thiamine-deficient alcoholics compared with controls. Cholinergic cell loss reflected the severity of cognitive dysfunction, but was not exclusive to patients with amnesia. Two thalamic nuclei are involved in relaying memories for storage and retrieval, the anterior and mediodorsal thalamic nuclei. While patients with Wernicke's encephalopathy often had neuronal loss in the mediodorsal nucleus, only patients with Korsakoff's psychosis had cell loss in both medial thalamic nuclei. The results suggest that cumulative lesions contribute to the amnesia seen in thiamine-deficient alcoholics, including deficits in serotonergic, cholinergic and medial thalamic pathways.

Acetylcholine↗
PubMed1993

Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain.

The basal nucleus of Meynert, incorporating the Ch4 group of cholinergic neurons, was examined in six patients with no signs of neurological abnormalities. The ages of the patients ranged from 20 to 80 years. Despite a number of descriptions of these neurons, few age-related studies have been dedicated to the analysis of the entire anteroposterior extent of the nucleus. Staining with cresyl violet and acetylcholinesterase histochemistry, alone or in combination, was used to identify the cytoarchitectural organization of the Ch4. Computer-assisted morphometry was used for three-dimensional visualization and quantitation. The three-dimensional computer reconstructions revealed a continuous ribbon of neurons with a highly variable density. Four distinct subregions could be clearly identified in all cases by their cytoarchitecture and cellular morphology, although these subgroups were different to those previously described. There were no quantitative differences between the hemispheres in volume, density or cell number of the Ch4, although equivalent levels varied in area and density. The measures were similar in all cases with the exception of the case aged 80 years old. The data demonstrate individual variability in three dimensions and confirm previous studies that found only a mild decline of the Ch4 in old age.

Acetylcholinesterase↗