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Biomedical subjects

C Bowen

Publications and source records attributed to C Bowen.

At least 19 recordsLinked to original sources
PubMed2006

Individual and multi-environment combined analyses identify QTLs for morphogenetic and reproductive development traits in white clover (Trifolium repens L.).

White clover (Trifolium repens L.) is a key component legume of temperate pasture agriculture and an important target for molecular marker-assisted plant breeding. A genetic map of white clover has been used to assess genetic control of agronomically important traits that vary in the F2(I.4RxI.5J) mapping family. Phenotypic analysis was performed for a range of vegetative morphogenesis traits (such as leaf area, internode length, plant height and plant spread) and reproductive morphogenesis and development traits (such as flowering date, floral intensity and seed yield), with both spatial and temporal replication. A multi-environment combined analysis (combined analysis) has been performed for traits assessed across multiple experimental datasets in order to identify consistent genetic effects. Quantitative trait locus (QTLs) were detected for the majority of traits, and the locations and magnitudes of QTL effects were compared between individual and combined analyses. This molecular genetic dissection of agronomic traits in white clover provides the basis for equivalent studies in more complex populations, design of marker-assisted selection strategies and comparative genetics with model legume species. Selection for QTLs derived from the combined analysis will permit robust improvement of phenotypic traits over different environments.

Chromosome Mapping↗
PubMed2005

High infection rates of Triatoma dimidiata are associated with low levels of Trypanosoma cruzi seroprevalence in Pedro Carbo, Ecuador. Use of a tc24 gene-based PCR approach.

In control programs for vectorial transmission of Chagas' disease, conventional microscopic procedures are generally performed to determine baseline levels of infectivity of vectors. Reported here are data using Polymerase Chain Reaction in the detection of Trypanosoma cruzi in Triatoma dimidiata, one of the principal vectors of Chagas' disease in Ecuador. The microscopy and PCR techniques showed a high percentage of vector infection in Pedro Carbo, province of Guayas (Ecuador), with 44.16% and 46.13% positive insects, respectively. This contrasted with the very low Chagas seropositivity recorded (0.5%). Since T. dimidiata was the only vector of the Chagas' disease found in Pedro Carbo and looking at the vector behavior, our data suggest that despite the high T. dimidiata infection, the low Chagas seropositivity detected is closely associated with the epidemiological and ecological context of T. dimidiata in Pedro Carbo.

Animals↗
PubMed2001

Androgen blocks apoptosis of hormone-dependent prostate cancer cells.

Androgen plays a critical role in the promotion and growth of prostate cancer. Androgen ablation has an expanding role in prostate cancer treatment and is now used to improve the efficacy of radiation therapy in addition to its role in treatment of metastatic disease. Here we show that androgen interferes with induction of prostate cancer cell death induced by a variety of stimuli. The effect of androgen on cell death occurs predominantly by interference with caspase activation and the inhibition of caspase cleavage in both the extrinsic and intrinsic cell death pathways. Androgen inhibited apoptosis induced by both tumor necrosis factor alpha (TNF-alpha) and by Fas activation with or without concomitant irradiation. An antiapoptotic effect was seen in the presence of R1881, dihydrotestosterone, and also 17beta-estradiol within 24 h of death induction. Sustained inhibition of apoptosis at 72 h was seen only with R1881, dihydrotestosterone, cyproterone acetate, and hydroxyflutamide. Androgen treatment inhibited activation of caspases-8, -7, and -9 by TNF-alpha +/- irradiation. Androgen attenuated BAX expression and blocked appearance of the proapoptotic p18 fragment of BAX. Androgen also abrogated BID cleavage induced by TNF-alpha + irradiation that contributed to a decrease in cytochrome c egress from mitochondria induced by TNF-alpha +/- irradiation. There was also decreased mitochondrial depolarization in response to TNF-alpha + irradiation. Production of the proapoptotic lipid metabolite ceramide was not affected by androgen, but androgen acted downstream from ceramide generation because R1881 blocked cell-death induction by bacterial sphingomyelinase. Inhibition of phosphoinositol-3-kinase activity by wortmannin induced apoptosis that was also blocked by androgen, but there was no effect on protein levels or phosphorylation of AKT, indicating that R1881 did not interact with survival signaling of phosphoinositol-3-kinase. Lastly, androgen inhibited activation of nuclear factor-kappaB during death induction, but the effect of androgen on cell death was not mediated by interference with the nuclear factor-kappaB pathway. The data suggest that androgen induced blockade of caspase activation in both intrinsic and extrinsic cell death pathways and thereby was able to protect prostate cancer cells from apoptosis induced by diverse stimuli.

Androgens↗
PubMed2001

Comparison of two floor mat lead dust collection methods and their application in pre-1950 and new urban houses.

This study investigated commercial floor mats as an alternative method to assess lead in residential dust in inner-city houses. Mats were placed for 3 weeks in interior entry-ways of 34 row houses built before 1950 and 17 new row houses in Baltimore City. A high volume sampler (an HVS3 floor model cyclone-based vacuum) and a hand-held portable cyclone sampler were used in the laboratory to collect side-by-side samples of mat dust. Both devices yielded comparable estimates of lead dust deposition, dust lead concentration, and dust deposition on field mat samples and had similar sampling efficiencies on mats spiked with various types of standard reference materials. The older houses had significantly higher daily lead dust deposition (mean = 130 micrograms/ft2/day by HVS3) than the newer houses (mean = 9 micrograms/ft2/day by HVS3), due to higher dust lead concentrations (mean = 1149 ppm vs mean = 107 ppm by HVS3) and not to differences in daily dust deposition (mean = 118 mg/ft2/day vs mean = 87 mg/ft2/day by HVS3) [corrected]. Mats were found to be a feasible method for the collection of dust that has accumulated for a known amount of time. Current wipe and vacuum methods do not allow for the estimation of dust deposition rates. Further research is needed to understand the role of floor mats as a risk assessment tool.

Air Pollution, Indoor↗
PubMed2001

International studies to compare methods for personal sampling of bitumen fumes.

A newly recommended Institute of Occupational Medicine (IOM) sampler, optimized for the inhalable fraction, was compared with 'total particulate' samplers currently used by five laboratories in different countries for the analysis of bitumen fumes. Using a laboratory fume generator, all samplers were uniformly exposed to bitumen fumes from typical USA bitumen (commercial Pen 65). The results show that, for laboratory-generated bitumen fumes, benzene-extractable inhalable particulate data for the IOM sampler are consistent with benzene soluble matter data from the other samplers. Direct comparison of the IOM sampler with the 37 mm closed-face cassette (USA sampler) using an identical protocol in a single laboratory gave a ratio of 1.05:1 (USA:IOM). Similarly, for total particulate matter, the standard previously recommended by the American Conference of Governmental Industrial Hygienists (ACGIH), an average value of approximately 1 between the IOM and the five samplers was obtained. For unadulterated bitumen fumes, the geometry of the cassettes does not appear to affect entry of the particles into the sampler. Field studies may show differences in results as other factors, e.g. wind and its effect on sampling efficiency, and also particulates originating from sources other than bitumen, such as dust, are involved. These will require thorough investigation prior to the assessment of the impact of the new sampler and prior to any reconsideration of occupational exposure limits taking into account practical feasibility. Other tests were conducted on the bitumen fume samples including total organic matter, simulated distillation and polycyclic aromatic compound analysis. These additional tests were performed on the fume collected on the filter plus the volatile portion that passed through the filter and was captured on various adsorbent materials. Protocols for sample collection and analysis varied in different countries with results reflective of these differences, suggesting the need for standardization.

Air Pollution, Indoor↗
PubMed2000

Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression.

NKX3.1 is a prostate-specific homeobox gene located on chromosome 8p21. In the mouse, Nkx3.1 has growth-suppressive and differentiating effects on prostatic epithelium. Mutations of the coding region of NKX3.1 were not found in human prostate cancer, failing to support the notion that NKX3.1 was a tumor suppressor gene. To study the expression o NKX3.1 protein in human tissues and prostate cancer, we derived a rabbit antiserum against purified recombinant NKX3.1. Among normal human tissues, NKX3.1 expression was seen in testis, in rare pulmonary mucous glands, and in isolated regions of transitional epithelium of the ureter. NKX3.1 was uniformly expressed in nuclei of normal prostate epithelial cells in 61 histological sections from radical prostatectomy specimens. We analyzed 507 samples of neoplastic prostate epithelium, most of which were contained on a tissue microarray that contained samples from different stages of prostatic neoplasia. We observed complete loss of NKX3.1 expression in 5% of benign prostatic hyperplasias, 20% of high-grade prostatic intraepithelial neoplasias, 6% of T1a/b samples, 22% of T3/4 samples, 34% of hormone-refractory prostate cancers, and 78% of metastases. Our data show that NKX3.1 expression is highly, but not exclusively, specific for the prostate. Loss of NKX3.1 expression is strongly associated with hormone-refractory disease and advanced tumor stage in prostate cancer (P < 0.0001).

Animals↗
PubMed2000

Effects of butorphanol and carprofen on the minimal alveolar concentration of isoflurane in dogs.

OBJECTIVE: To evaluate the effects of butorphanol and carprofen, alone and in combination, on the minimal alveolar concentration (MAC) of isoflurane in dogs. DESIGN: Randomized complete-block crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURE: Minimal alveolar concentration of isoflurane was determined following administration of carprofen alone, butorphanol alone, carprofen and butorphanol, and neither drug (control). Anesthesia was induced with isoflurane in oxygen, and MAC was determined by use of a tail clamp method. Three hours prior to induction of anesthesia, dogs were fed a small amount of canned food without any drugs (control) or with carprofen (2.2 mg/kg of body weight [1 mg/lb]). Following initial determination of MAC, butorphanol (0.4 mg/kg [0.18 mg/lb], i.v.) was administered, and MAC was determined again. Heart rate, respiratory rate, indirect arterial blood pressure, endtidal partial pressure of CO2, and saturation of hemoglobin with oxygen were recorded at the time MAC was determined. RESULTS: Mean +/- SD MAC of isoflurane following administration of butorphanol alone (1.03 +/- 0.22%) or carprofen and butorphanol (0.90 +/- 0.21%) were significantly less than the control MAC (1.28 +/- 0.14%), but MAC after administration of carprofen alone (1.20 +/- 0.13%) was not significantly different from the control value. The effects of carprofen and butorphanol on the MAC of isoflurane were additive. There were not any significant differences among treatments in regard to cardiorespiratory data. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of butorphanol alone or in combination with carprofen significantly reduces the MAC of isoflurane in dogs; however, the effects of butorphanol and carprofen are additive, not synergistic.

Animals↗
PubMed2000

Gradient-induced acoustic and magnetic field fluctuations in a 4T whole-body MR imager.

Both the acoustic and magnetic fluctuation frequency response functions for a Siemens AS25 body gradient coil inside a 4 Tesla whole-body MR system were measured and analyzed in this study. In an attempt to correlate the acoustic noise inside the gradient coil with magnetic field oscillations, triangular and trapezoidal gradient impulses of varying amplitudes and widths were used to excite the gradient coil. The acoustic and magnetic responses to these inputs were measured. The results show the existence of discrete resonances in both acoustic and uniform magnetic field fluctuation spectra, while gradient magnetic field fluctuation spectra show no such resonances. In addition, the dominant amplitude peaks in spectra fluctuate similarly with respect to trapezoidal gradient impulse flat-top widths. This implies that these phenomena are correlated, and that the trapezoidal impulse flat-top width may be used as a way to suppress both acoustic noise and uniform magnetic field oscillations.

Electromagnetic Fields↗
PubMed1999

Tumor necrosis factor-alpha sensitizes prostate cancer cells to gamma-irradiation-induced apoptosis.

LNCaP prostate cancer cells are highly resistant to induction of programmed cell death by y-irradiation and somewhat sensitive to the death-inducing effects of tumor necrosis factor (TNF)-alpha. Simultaneous exposure of LNCaP cells to TNF-alpha and 8 Gy of irradiation was synergistic and resulted in a 3-fold increase of apoptotic cells within 72 h compared to TNF-alpha alone. It appeared that TNF-alpha sensitized the cells to irradiation because, when cells were irradiated 24 h after exposure to TNF-alpha, increased cell death was observed. In contrast, irradiation delivered 24 h prior to TNF-alpha exposure did not result in more cell death than after TNF-alpha alone. TNF-alpha induced expression of its own mRNA, but TNF-alpha mRNA induction was neither induced nor enhanced by irradiation. Activation of the transcription factor nuclear factor kappaB can be induced by TNF-alpha and has a modulating antiapoptotic effect. But enhancement of TNF-alpha-induced cell death by irradiation did not result from altered activation of nuclear factor kappaB. TNF-alpha treatment of LNCaP cells resulted in partial activation of caspase-8 and -6 but not caspase-3. There was only minimal poly(ADP-ribose) polymerase cleavage seen in LNCaP cells after exposure to both TNF-alpha and irradiation at 72 h, a time when 60% of the cells were apoptotic. Experiments with peptide inhibitors of cysteine and serine proteases suggested that caspases were the predominant mediators of apoptosis induced by TNF-alpha alone but that serine proteases contributed significantly to cell death induced by TNF-alpha plus irradiation. TNF-alpha increased production of ceramide in LNCaP cells 48 h after exposure. Although irradiation alone had no effect on ceramide production in LNCaP cells, TNF-alpha plus irradiation induced significantly more ceramide than TNF-alpha alone. Ceramide production did not occur immediately after exposure to TNF-alpha, but rather was delayed such that ceramide levels were increased only 24 h after exposure to apoptotic stimuli. Moreover, non-toxic levels of exogenous C2-ceramide sensitized LNCaP cells to irradiation similarly to TNF-alpha, suggesting that one mechanism by which LNCaP cells were sensitized to irradiation was by increased intracellular ceramide. Hence, ceramide generation is a critical component in radiation-induced apoptosis in human prostate cancer cells. Inhibition of ceramide generation may provide a selective advantage in the development of radioresistance in prostate cancer.

Apoptosis↗
PubMed1999

Synthesis of procaspases-3 and -7 during apoptosis in prostate cancer cells.

Cells differ in the time required to execute cell death after receipt of a death signal. One reason may be the requirement for de novo synthesis of components of the death pathway. TSU-Pr1 prostate cancer cells treated with okadaic acid demonstrated activation of caspase-3, PARP cleavage, and nuclear fragmentation by 24 h and apoptosis by 72 h. Levels of procaspase-3 and procaspase-7, the precursor molecules of two effector caspases, were not depleted during apoptosis. Levels of procaspase-3 and -7 mRNA increased steadily in TSU-Pr1 cells up to 72 h after exposure to okadaic acid. Nuclear run-off experiments showed that the increase in mRNA was not due to transcriptional activation of caspase-3 and -7 mRNA. Antisense caspase-3 and caspase-7 oligodeoxynucleotides caused a depletion of procaspases-3 and -7 and a delay in apoptosis of TSU-Pr1 cells. Caspase antisense oligodeoxynucleotides inhibited apoptosis to a similar extent as peptide inhibitors of cysteine proteases. Synthesis of procaspases-3 and -7 was necessary to sustain programmed cell death in TSU-Pr1 prostate cancer cells.

Apoptosis↗
PubMed1999

RB status as a determinant of response to UCN-01 in non-small cell lung carcinoma.

7-Hydroxystaurosporine (UCN-01), a protein kinase inhibitor in clinical development, demonstrates potent antineoplastic activity. To determine whether specific genetic abnormalities would modulate the response to UCN-01, a model of human non-small cell lung carcinoma (NSCLC) cell lines with differential abnormalities of p16CDKN2, RB, and p53 was used for these studies. Cell growth was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and cell cycling was studied using flow cytometric analysis of DNA content. Changes in protein levels and phosphorylation were assessed by Western blotting. In cell lines expressing wild-type RB (A549 and Calul), UCN-01 treatment resulted in dose-dependent growth inhibition, arrest of cells in G1, and a reduction of cells in S phase. p16CDKN2-null cells showed similar growth inhibition to normal fetal lung fibroblasts. UCN-01-induced growth arrest was accompanied by induction of p21CDKN1 and a shift of Rb to the hypophosphorylated state in both p53 wild-type and mutant cell lines. In contrast, UCN-01 treatment of the RB-null cell line H596 resulted in less growth inhibition. To test the role of RB in response to UCN-01, effects of treatment were examined in two human isogenic models of RB expression: the bladder cancer cell line 5637 (RB-null) and the prostate cancer cell line DU-145 (RB-mutant). In the Rb-expressing 5637 subline (RB5), UCN-01 treatment resulted in Rb hypophosphorylation and an accumulation in G1 in contrast to the parent line. Similarly, the wild-type Rb-expressing DU-145 sublines (DU1.1 and B5) showed increased G1 arrest compared with the parent cells. We conclude that UCN-01-induced G1 arrest can occur in cells null for p53 and p16CDKN2, and that RB status influences the ability of UCN-01 to induce a G1 arrest. These data suggest that the molecular profile of cell cycle regulating genes in individual tumors may predict responsiveness and provide insight into optimal therapeutic application of this new antineoplastic agent.

Alkaloids↗
PubMed1998

Radiation-induced apoptosis mediated by retinoblastoma protein.

The role of the retinoblastoma gene product, RB, in transmitting the signals of apoptosis is unclear, but RB is considered to be antiapoptotic because RB mediates cell cycle arrest that also can interrupt intracellular signaling pathways leading to apoptosis. Gamma-radiation can cause apoptosis, the process of programmed cell death, via several mechanisms including DNA damage, ceramide production, and the generation of free radical oxygen species. We investigated the effect of RB on radiation-induced apoptosis by restoring normal RB expression in DU-145 prostate cancer cells that have one deleted and one truncated RB gene. DU-145 cells are highly resistant to apoptosis induced either by radiation or by the addition of ceramide. Two independently derived RB-positive DU-145 derivative cell lines underwent apoptosis after irradiation or exposure to the cell permeable C2-ceramide. Apoptosis in the RB-positive cell lines was not associated with major changes in the cell cycle response to irradiation. RB-mediated apoptosis occurred in the absence of expression of caspases 8, 6, 3, and 7 and without detectable cleavage of poly(ADP)ribose polymerase. However, a specific inhibitor of serine proteases, Na-p-Tosyl-L-lysyl-chloromethyl ketone, inhibited radiation-induced apoptosis in DU-145 cells expressing RB. Radiation-induced apoptosis was preceded by an increase in JUN protein expression and accompanied by activation of the stress-related JUN kinase. Our data show that RB is proapoptotic in DU-145 cells and acts upstream of JUN expression and JNK activation.

Apoptosis↗
PubMed1998

Ductography for nipple discharge: no replacement for ductal excision.

BACKGROUND: Current management of nipple discharge depends on clinical history to distinguish pathologic from physiologic discharge. We investigated whether ductography supplied additional information in the decision for surgery and/or the localization of pathologic lesion. METHODS: A retrospective review of patients with a presenting complaint of nipple discharge seen at the Lynn Sage Breast Center was conducted from January 1995 to June 1996. Medical records, pathology, and ductograms were reviewed. RESULTS: Of 91 patients with nipple discharge, 49 met the criteria for physiologic discharge and 42 had pathologic discharge. Eleven with physiologic discharge had ductograms; none were abnormal. Four of 20 preoperative ductograms were normal but showed intraductal papillomas at the time of surgery; 6 of 20 (30%) had multiple lesions. Four lesions on ductograms did not demonstrate corresponding lesions in the surgical specimen. It is uncertain whether this is due to a missed lesion or a false-positive ductogram. CONCLUSIONS: Modern ductography does not reliably exclude intraductal pathology and is not a substitute for surgery in patients with pathologic discharge. Its utility is in identifying multiple lesions or those with lesions in the periphery of the breast.

Adult↗
PubMed1998

Metabolic mapping of the effects of oral alcohol self-administration in rats.

The functional effects of the voluntary consumption of ethanol in rats were investigated using the quantitative autoradiographic 2-[14C]deoxyglucose method for measurement of rates of local cerebral glucose utilization. A modified sucrose-substitution procedure was used to train three groups of Wistar rats to self-administer water, a 5% sucrose solution, or a 10% ethanol/5% sucrose solution in daily sessions. Once stable rates of consumption were established, the 2-[14C]deoxyglucose method was applied immediately after completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g/kg (n = 6) on the day of the procedure or a comparable volume of sucrose solution (n = 6) or water (n = 5). Rates of local cerebral glucose utilization in rats that ingested water did not differ from those that rats consumed a 5% sucrose solution. In contrast, voluntary ethanol consumption produced a highly discrete pattern of changes in rates of glucose utilization. Ethanol ingestion increased cerebral metabolism, as compared with rates of metabolism in rats that consumed either water or sucrose in the rostral pole and shell of the nucleus accumbens, medial prefrontal cortex, lateral septum, basolateral and central nuclei of the amygdala, substantia nigra, and the ventral tegmental area. This pattern of alterations in functional activity is distinctly different from that observed when equivalent doses of ethanol are administered acutely, emphasizing the importance of self-administration in determining the changes in glucose utilization. Furthermore, within the nucleus accumbens, glucose utilization was selectively augmented in the rostral pole and shell subterritories, whereas cerebral metabolism in the core was unaffected. Finally, these data demonstrate that it is the simultaneous activation of an interconnected network of limbic brain regions that serves as the substrate of the effects of voluntarily ingested ethanol.

Alcohol Drinking↗
PubMed1996

Educating teachers in children's illnesses: a study.

This study was carried out in response to teachers' concerns about emergency situations involving children with asthma, epilepsy and diabetes. Data were collected on whether teachers had received advice on coping with such emergencies in either their basic teacher training or in-service training, and whether they felt competent to cope with emergencies which could arise. The research found that no overall policy existed and that teachers would appreciate regular updates on the care of these children. The author also describes training sessions arranged following the analysis of the study.

Adult↗