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J Foley

Publications and source records attributed to J Foley.

At least 37 records · Page 2Linked to original sources

The use of dimethylmethylene blue for virus photoinactivation of red cell suspensions.

Phenothiazine dyes and light have been known to have virucidal properties for over seventy years. This review will describe recent progress in the use of one phenothiazine dye, dimethyl-methylene blue, for photo-inactivation of a number of RNA and DNA viruses in red cell suspensions under conditions that minimally affect red cell in vitro properties during 42-day 1-6 degrees C storage. Dimethylmethylene blue has a higher affinity for nucleic acid than the closely related phenothiazine, methylene blue. Virus photoinactivation appears to be mediated by singlet oxygen. The kinetics of photoinactivation depends on the virus studied, but for a given virus, is similar for both intracellular and extracellular forms. The similarity for inactivation of intracellular and extracellular virus suggests that a common target, such as nucleic acid, is involved. Finally, lymphocytes, which can harbour transfusion-associated viruses and can mediate transfusion-associated-graft-versus host disease, are sensitive to dimethylmethylene blue photoinactivation under virucidal conditions.

Animals↗

K-ras and p53 in pancreatic cancer: association with medical history, histopathology, and environmental exposures in a population-based study.

Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.

Aged↗

Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site.

PTHrP gene expression was evaluated in a murine keratinocyte line, Pam 212K, transformed with E1A and ras. We found that the 12S-E1A oncogene, with or without ras transformation, markedly reduced PTHrP mRNA expression. Using transient transfection assays, we found that the 12S isoform repressed activity from a 5'PTHrP-driven reporter gene. E1A-induced repression of PTHrP reporter constructs appears to be mediated by sequences within minimal promoter region. The 13S-E1A isoform did not repress PTHrP reporter gene activity, and a 13S-deletion mutant that lacked the repressor domains activated a subset of reporter constructs. Mutation of an Ets-1 binding site upstream of the basal promoter substantially decreased activation of reporter constructs by this 13S-deletion mutant. These findings suggest that the E1A oncoprotein may serve as a model for both activation and repression of PTHrP gene expression.

Adenovirus E1A Proteins↗

Gastric gas and fluid emptying assessed by magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to characterize the volumes and rates of gastric emptying of both liquid and gas following the ingestion of beverages of varying carbonation and carbohydrate levels. Eight subjects drank 800 ml each of four test beverages in a counterbalanced order: water, a non-carbonated carbohydrate-electrolyte solution (NC), a lightly carbonated carbohydrate-electrolyte solution (PC), and a carbonated cola (CC). T2-weighted, echoplanar images (25-30 contiguous slices, 1 cm thick, 256 x 128 matrix, TE = 80, 40 cm FOV) of the abdomen were collected at minutes 3,110, 20, 30, 45, and 60 following beverage ingestion. Images were analyzed for gas and liquid volumes. Water and NC emptied the most rapidly, with half times of 21(3) and 31(3) min, respectively [mean (SE)]. PC emptied significantly slower [47 (6) min] and CC slower yet [107 (8) min]. The carbonation content of the beverage accounted for 84% of the variation in emptying time, whereas carbohydrate content did not account for any significant variation. The gastric gas volume of the CC was higher at 2 min post-ingestion compared with all other drinks; however, the rate of emptying of the gas was the same among all beverages. Significantly greater total gastric volumes (gas+ liquid) were associated with the ingestion of CC, and accordingly produced a greater severity of gastric distress, as evaluated with a gastric distress inventory. The high gastric gas volumes (approximately 600 ml) after ingestion of CC suggested a potential source of error in body composition using standard hydrostatic weighing methods. This prediction was tested in nine additional subjects. Ingestion of 800 ml of CC prior to hydrostatic weighing resulted in a 0.7% underestimate of body density and thus an 11% overestimate of percentage body fat compared to measurements made before beverage consumption.

Adult↗

Development of a teaching module for quality-of-life assessment of terminal patients. The AACE Multi-Institutional Palliative Cancer Education Section. American Association for Cancer Education.

To enhance the teaching of students to assess quality of life of patients with serious disease, the AACE Palliative Cancer Education Section has developed a teaching module. The module, which focuses on four desired learning objectives, is to be used in an hour-long small-group session. The authors describe the development of the module, as well as its objectives, teaching method, evaluation, and future challenges.

Curriculum↗

Educating lay carers of people with learning disability in epilepsy awareness and in the use of rectal diazepam: a suggested teaching protocol for use by healthcare personnel.

A high proportion of people with learning disabilities have epilepsy and often their epilepsy is of an intractable nature. Nurses within the large learning disability institutions are obliged, on a regular basis, to administer rectal diazepam to control these patients' serial seizures. As a result of the "community care" initiative, the process of discharging adult people from institutions into care settings in the community is underway. Consequently, and increasingly, the learning disabled are being cared for by non-medical/non-nursing (lay) community home carers who are required to gain a working knowledge of epilepsy as well as a degree of proficiency in the first aid management of seizures and in the use of rectal diazepam. Medical and nursing staff involved in the care of adults with learning disability are now liable to be approached by lay care organisations for appropriate training. This article, therefore, will outline the training programme employed at Gogarburn Hospital to educate lay community care staff in general epilepsy awareness and in the administration of rectal diazepam to adults with learning disability and epilepsy. This programme could be adapted and implemented by colleagues in their own areas.

Administration, Rectal↗

Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses.

Feline infectious peritonitis virus (FIPV) strains from six cats and three different geographic areas were compared genetically with feline enteric coronavirus (FECV) isolates obtained from cats inhabiting the same environments. Sequence comparisons were made from 1.2- to 8.9-kb segments on the 3' end of the genome. FECV/FIPV pairs from the same catteries or shelters were 97.3-99.5% related but were genetically distinct from FIPV and FECV strains obtained from cats living in geographically distinct environments. The high genetic similarity between FECVs and FIPVs from the same environment strongly suggested a common ancestry. Based on the presence of deletion mutations in the FIPVs and not in the FECVs, it was concluded that FIPVs evolved as mutants of FECVs. The mutations are deletions in the FIPVs and not insertions in the FECVs since similar sequences are present in other strains that have segregated earlier from a common ancestor. Therefore, the order of descent is form FECV to FIPV. Mutations unique to FIPVs were found in open reading frames (ORFs) 3c in 4 of 6 isolates and/or 7b in 3 of 6 isolates. When the study was extended to include 7 additional FIPV isolates, 11/13 of the FIPVs sequenced were found to have mutated 3c ORFs.

Amino Acid Sequence↗

Effect of decreased milking frequency of cows in late lactation on milk somatic cell count, polymorphonuclear leucocyte numbers, composition and proteolytic activity.

The effects of reducing the frequency of milking of cows in late lactation on milk somatic cell count (SCC), polymorphonuclear leucocyte (PMN) content, chemical composition and proteolytic activity were investigated. Intermittent milking is frequently practised by Irish farmers in late lactation, and the objective of this study was to determine whether this procedure could be linked to altered quality of milk. Seventeen Holstein Friesian cows in late lactation (> 215 d in milk) were assigned to two treatment groups, and were either milked twice a day until drying-off (control group) or milked intermittently as the yield fell (test group). Milk composition and enzymic characteristics were measured on two occasions. At the first sampling, day 7, test cows were on once daily milking and at the second, day 15, the test cows were being milked every second day. Milk yields were significantly lower in test than control animals and decreased between days 7 and 15 in both groups. Milk SCC and PMN levels were increased on reducing milking frequency and, at day 15, the increase was not linked to decreased milk yield. Milk lactose levels were significantly decreased and pH, alpha-lactalbumin levels, plasmin activity and plasminogen activity significantly increased by reducing milking frequency. In conclusion, reduced frequency of milking in late lactation leads to the production of milk that is abnormal in character and this may be linked to reduced quality of dairy products manufactured from such milk.

Animals↗

The Epilepsy Outcome Scale: the development of a measure for use with carers of people with epilepsy plus intellectual disability.

This paper describes the development of a new scale for the assessment of epilepsy in people with learning disabilities. The scale was developed and validated in consultation with principal carers, and reflects their concerns about seizures, their impact and their treatment. Further testing of the scale revealed high internal consistency, testretest reliability and a robust factor structure. The scale can be completed in 5-10 min and may be useful as an outcome measure both in clinical practice and in research trials.

Adaptation, Psychological↗

PTHrP regulates epidermal differentiation in adult mice.

Emerging evidence suggests that parathyroid hormone-related peptide (PTHrP) serves as a regulator of the development and/or differentiation of a number of organs, including endochondral bone, the tooth, and the mammary gland. Although disruption of the PTHrP gene by homologous recombination results in a lethal chondrodystrophy, PTHrP-knockout mice that have been rescued by the transgenic replacement of the peptide in cartilage display abnormalities in ectodermally derived structures including the skin. At 6-8 wk of age, these rescued PTHrP-knockout mice displayed a markedly thinned epidermis and striking hyperkeratosis, hypoplastic sebaceous glands, and a fibrotic dermis. In contrast, transgenic mice that overexpress PTHrP by virtue of the human keratin-14 promoter displayed a thickened ventral epidermis with marked acanthosis and papillomatosis, hyperplastic sebaceous glands, and a cellular dermis. The absence of PTHrP appeared to result in the reduction of the basal keratinocyte compartment and premature acquisition of suprabasal and granular differentiation markers, whereas overexpression of the peptide generated reciprocal findings. No difference in the epidermal proliferation rate was found in PTHrP-null skin and although an increase was observed in keratin 14-PTHrP transgenic animals, their epidermis did not express the hyperplasia marker K6. Finally, the replacement of PTHrP in the basal keratinocytes of rescued PTHrP-knockout mice under the direction of the keratin 14 promoter reversed the abnormalities seen in PTHrP-null skin. These findings suggest that PTHrP regulates the rate of keratinocyte differentiation in the skin of adult mice.

Aging↗

A sterile syringe for every drug user injection: how many injections take place annually, and how might pharmacists contribute to syringe distribution?

Our objectives were to estimate the annual number of injections by injection drug users (IDUs) in the United States of America, and to describe the potential role of pharmacists in providing IDUs with a sterile syringe for every injection. We estimated the number of annual injections by IDUs for the United States, selected U.S. states, and selected U.S. cities according to the following formula: number of injections per year = (number of IDUs) x (average number of injections per IDU per day) x 365. Data were obtained from published articles, personal communications with local experts, and selected national databases. We also reviewed published and unpublished studies of pharmacy kits, pharmacist attitudes, and pharmacist practices in the United States and abroad. Between 920 million and 1.7 billion injections by IDUs take place each year in the United States. We estimated 12 million injections per year in San Francisco and >80 million in New York City. A similar number of syringes would be needed to satisfy the goal of a sterile syringe for every injection. Pharmacy-based strategies, including the sale of kits for injection drug use, have provided sterile syringes to IDUs in Europe, Australia, and New Zealand. Modification of laws restricting syringe purchase and possession has led to marked increases in purchase of syringes from pharmacies and reductions in needle-sharing. In conclusion, large numbers of syringes would be required to provide a sterile syringe for every injection, but significant numbers of pharmacists seem to be willing to play a central role in syringe sale and distribution. Outreach programs should emphasize that using a sterile syringe for every injection is the optimal HIV prevention practice for IDUs who cannot or will not stop injecting. Pharmacy-based syringe sale or distribution has the potential to augment current efforts to prevent HIV infection in IDUs, their sex partners, and their children.

Australia↗

Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes.

A cDNA encoding a P450 monooxygenase was amplified from reverse transcribed rat heart and liver total RNA by polymerase chain reaction using primers based on the 5'- and 3'-end sequences of two rat pseudogenes, CYP2J3P1 and CYP2J3P2. Sequence analysis revealed that this 1,778-base pair cDNA contained an open reading frame and encoded a new 502 amino acid protein designated CYP2J3. Based on the deduced amino acid sequence, CYP2J3 was approximately 70% homologous to both human CYP2J2 and rabbit CYP2J1. Recombinant CYP2J3 protein was co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 insect cells using a baculovirus expression system. Microsomal fractions of CYP2J3/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolized arachidonic acid to 14,15-, 11,12-, and 8, 9-epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid as the principal reaction products (catalytic turnover, 0.2 nmol of product/nmol of cytochrome P450/min at 37 degrees C). Immunoblotting of microsomal fractions prepared from rat tissues using a polyclonal antibody raised against recombinant CYP2J2 that cross-reacted with CYP2J3 but not with other known rat P450s demonstrated abundant expression of CYP2J3 protein in heart and liver. Immunohistochemical staining of formalin-fixed paraffin-embedded rat heart tissue sections using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection localized expression of CYP2J3 primarily to atrial and ventricular myocytes. In an isolated-perfused rat heart model, 20 min of global ischemia followed by 40 min of reflow resulted in recovery of only 44 +/- 6% of base-line contractile function. The addition of 5 microM 11, 12-epoxyeicosatrienoic acid to the perfusate prior to global ischemia resulted in a significant 1.6-fold improvement in recovery of cardiac contractility (69 +/- 5% of base line, p = 0.01 versus vehicle alone). Importantly, neither 14,15-epoxyeicosatrienoic acid nor 19-hydroxyeicosatetraenoic acid significantly improved functional recovery following global ischemia, demonstrating the specificity of the biological effect for the 11, 12-epoxyeicosatrienoic acid regioisomer. Based on these data, we conclude that (a) CYP2J3 is one of the predominant enzymes responsible for the oxidation of endogenous arachidonic acid pools in rat heart myocytes and (b) 11,12-epoxyeicosatrienoic acid may play an important functional role in the response of the heart to ischemia.

8,11,14-Eicosatrienoic Acid↗

Insulin resistance.

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Diabetes Mellitus, Type 2↗

CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance.

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. In addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport.

8,11,14-Eicosatrienoic Acid↗

Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas.

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homolog (CYP2J3). Immunoblotting studies using a polyclonal antibody raised against recombinant human CYP2J2 confirmed CYP2J protein expression in human and rat pancreatic tissues. Immunohistochemical staining of formalin-fixed paraffin-embedded rat and human pancreas using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J2 protein expression was highly localized to cells in the islets of Langerhans, with minimal staining in pancreatic exocrine cells. Colocalization studies using antibodies to the glucagon, insulin, somatostatin, and pancreatic polypeptide as markers for alpha-, beta-, delta-, and PP cells, respectively, showed that CYP2J protein expression was abundantly present in all four cell types, but was highest in the glucagon-producing alpha-cells. Direct evidence for the epoxidation of arachidonic acid by pancreatic cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in vivo in human and rat pancreas by gas chromatography/mass spectrometry. Importantly, the levels of immunoreactive CYP2J2 in different human pancreatic tissues were highly correlated with endogenous epoxyeicosatrienoic acid concentrations. We conclude that human and rat pancreas contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is highly localized to islet cells. These data together with previous work showing effects of epoxyeicosatrienoic acids in stimulating insulin and glucagon secretion from isolated rat pancreatic islets support the hypothesis that epoxygenase products may be involved in stimulus-secretion coupling in the pancreas.

8,11,14-Eicosatrienoic Acid↗

Strength of core build-up materials in endodontically treated teeth.

PURPOSE: To compare the in vitro strength of a reinforced glass ionomer and a light-cured glass ionomer used as an alternative to amalgam in core construction to restore endodontically treated mandibular molar teeth. MATERIALS AND METHODS: The root canals of 120 extracted human mandibular molar teeth were prepared chemomechanically and obturated with laterally condensed cold gutta-percha. The crown of each tooth was sectioned leaving only one cusp standing. Gutta-percha was removed from the pulp chamber in all teeth. The volume of the pulp chamber was measured and the teeth ranked in ascending order of chamber volume. The specimens were divided into six groups of 20, allocating teeth with similar chamber volumes into each group. In three of the groups, gutta-percha was removed from the coronal 3-4 mm of each root canal. The teeth were restored with one of three materials, a cermet cement (Ketac-Silver), a resin-reinforced glass ionomer (Vitremer), or amalgam (Contour). Core preparation was carried out after 48 hours, reducing each core height to 6 mm. The specimens were thermocycled for 24 hours and then mounted in dental stone. A control group of 20 unrestored human mandibular molars was mounted in cold cure acrylic. Each tooth was tested in a Nene machine with a compressive load applied at 90 degrees to the occlusal surface at a crosshead speed of 5 mm/minute. RESULTS: There was no statistically significant difference between the experimental groups (P > 0.05), but the control group was significantly stronger (P < 0.001). Extension of core material into the coronal root canal system did not increase the fracture resistance of any of the experimental materials. Regression analysis of the results revealed no correlation between the volume of the pulp chamber and the load to fracture.

Cermet Cements↗

Parathyroid hormone-related protein gene expression in human squamous carcinoma cells is repressed by mutant isoforms of p53.

Parathyroid hormone-related protein (PTHrP) is a normal secretory product of a variety of squamous epithelia, including epidermal keratinocytes. Only a subset of squamous carcinomas, however, express the gene at levels sufficient to cause humoral hypercalcemia. In the present study, comparison of PTHrP expression levels with p53 functional status in a series of squamous carcinoma lines has revealed an association between expression of specific mutant isoforms of p53 and very low levels of PTHrP mRNA. Evaluation of p53 isoforms with mutations in codons 248 and 273 showed them to be capable of repressing PTHrP gene expression in a high-expressing, p53-negative squamous line by approximately 50%. Conversely, inactivation of an endogenous mutant p53 with E1B proteins resulted in an increase in PTHrP expression in a low-expressing cell line. Subsequent analysis of promoter-specific PTHrP transcripts in a p53-negative squamous line transfected with mutant p53 isoforms suggested that down-regulation occurred primarily at the two TATA-based promoters. Direct testing of a murine PTHrP reporter construct in transient transfection assays confirmed the capacity of the 248 and 273 mutants to repress this TATA-based promoter, although only about half as effectively as wild-type p53.

Adenovirus E1B Proteins↗