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Biomedical subjects

B A Kelly

Publications and source records attributed to B A Kelly.

12 recordsLinked to original sources
PubMed2004

Aortic adaptation to pregnancy: elevated expression of matrix metalloproteinases-2 and -3 in rat gestation.

The maternal aorta undergoes substantial functional and structural adaptation in pregnancy. Both aortic diameter and compliance are increased and studies of animal and human gestation indicate that these changes are initiated in early pregnancy and maintained until delivery. The mechanisms underlying aortic adaptation in normal pregnancy remain largely unknown but matrix metalloproteinase enzymes (MMP) are likely to play a key role. Gene expression of candidate MMP and specific tissue inhibitors of MMP (TIMP) were investigated in non-pregnant, pregnant (days 7, 14, 21) and postpartum (day 7) rat aorta using real-time PCR. Of the gene transcripts studied (MMP-2, -3, -7, -9, -12, -13, MT1MMP, TIMP-1, -2) in rat aorta, only MMP-3 was significantly elevated with a 24-fold increase observed in late gestation compared to virgin control (P = 0.0001). MMP-2 mRNA appeared constitutively expressed and unchanged at time-points studied, but MMP-2 activity as assessed by gelatin zymography suggested further modulation after transcription and/or post-translation in rat aorta with activity increased in early pregnancy (P < 0.01, compared to virgin control). These data suggest that MMP-2 and MMP-3 may contribute to adaptive processes in the maternal rat aorta at different gestations and further support a role for this family of enzymes in physiological vascular remodelling.

Animals↗
PubMed2003

Gestational profile of matrix metalloproteinases in rat uterine artery.

Mechanisms underlying structural reorganization of the uterine artery in pregnancy remain largely unknown. Matrix metalloproteinases (MMPs) which are involved in degradation of vascular wall matrix are likely to play a key role. In this investigation of rat uterine artery, key MMPs and the specific tissue inhibitors of MMPs (TIMPs) together with three housekeeping genes were studied before, during and after pregnancy, using real time PCR. Data were analysed by partial least squares analysis as well as by conventional univariate methods. Each gene studied [MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, MMP-13, membrane-type 1 (MT1)-MMP, TIMP-1, TIMP-2, GAPDH, cyclophilin and beta-actin] increased in late pregnancy (day 21). MMP-2, MT1MMP, MMP-3 and TIMP-1 transcripts were also elevated at day 7. TIMP-1 and MMP-3 mRNA expression returned to virgin control values in the post-partum, whereas others remained elevated or increased further (MMP-9, MMP-13). Gelatin zymography showed maximum elevation of MMP-2 at day 21. A novel 43-45 kDa gelatinolytic doublet was observed which increased in density with gestation and may represent an active MMP-2 fragment. Together, these data strongly suggest that MMPs and TIMPs are likely to play an important role in remodelling uterine arteries in rat pregnancy and may represent means by which vasodilatation is maintained in later pregnancy. Continued elevated levels of some MMPs post-partum may contribute to vessel regression and return to a non-pregnant physiological state.

Animals↗
PubMed2000

Preparing a cost analysis for the section of medical physics-guidelines and methods.

Radiation oncology is a highly complex medical specialty, involving many varied routine and special procedures. To assure cost-effectiveness and maintain support for the medical physics program, managers are obligated to analyze and defend all aspects of an institutional billing and cost-reporting program. Present standards of practice require that each patient's radiation treatments be customized to fit his/her particular condition. Since the use of personnel time and other resources is highly variable among patients, graduated levels of charges have been established to allow for more precise billing. Some radiation oncology special procedures have no specific code descriptors; so existing codes are modified or additional information attached in order to avoid payment denial. Recent publications have explored the manpower needs, salaries, and other resources required to perform radiation oncology "physics" procedures. This information is used to construct a model cost-based resource use profile for a radiation oncology center. This profile can be used to help the financial officer prepare a cost report for the institution. Both civil and criminal penalties for Medicare fraud and abuse (intentional or unintentional) are included in the False Claims Act and other statutes. Compliance guidelines require managers to train all personnel in correct billing procedures and to review continually billing performance.

Costs and Cost Analysis↗
PubMed1998

Managing metabolic model deficiencies for routine radiation protection purposes at a thorium dioxide facility.

At a metallurgical facility using thorium dioxide feed materials, a number of conventional direct- and indirect-bioassay methods were potentially suitable monitoring methodologies when industry-standard dose assessment methodologies were based upon ICRP recommendations issued in 1959. When the ICRP recommended a different dose assessment methodology in 1977, the intake limits for thorium dropped significantly, and conventional bioassay methods for routine monitoring were rendered ineffective. While determining the technical basis for its air monitoring program, the facility noted that the radioactive materials used as feed to the process were highly insoluble. Therefore, their solubility in simulated lung fluids was determined. The results of this determination indicated that the facility's materials, if inhaled, dissolve in the lung at a half-time that is significantly longer than that contained in international consensus standards for Y-class compounds. They also indicated that the secondary dose limits, if adjusted to eliminate the dose contribution from translocated radionuclides, should be higher, and that a derived air concentration based upon more recent international recommendations is more appropriate for use in the facility's routine monitoring program.

Biological Assay↗
PubMed1994

Production, partial characterization, and potential diagnostic use of salicylate hydroxylase from Pseudomonas putida UUC-1.

An unusual strain of Pseudomonas putida UUC-1 capable of growth at high salicylate concentration (10 gl-1) was investigated with the aim of developing an assay and a biosensor system for determining salicylate in body fluids by utilizing the salicylate hydroxylase enzyme. Medium and growth condition optimization were carried out under chemostat conditions. The highest biomass yield was at 4.0 gl-1 salicylate, 25 degrees C, pH 6.5, and 0.2 h-1 dilution rate. Growth occurred at up to 0.45 h-1 dilution rate, producing 236 Ul-1 enzyme activity and an output of 424 U h-1. The activity and productivity were higher than any reported in the literature for this enzyme. It had a Km value of 2.07 +/- 0.32 microM and an M(r) of approximately 43,000. In addition, its specific activity in the crude extract (0.8-0.9 U mg-1 protein) was similar to the commercially available enzyme. No plasmid DNA was detected in this strain, and no salicylate-negative isolates were obtained when curing with mitomycin C. It is therefore proposed that our strain has a chromosomally located inducible salicylate hydroxylase gene that enables it to grow at high salicylate. This strain also offers a means of cheaply producing large quantities of the enzyme through standard fermentation techniques.

Biosensing Techniques↗
PubMed1993

Dihydrofolate reductase synthesis in continuous culture using a methotrexate-resistant Escherichia coli.

A methotrexate-resistant strain of Escherichia coli Type I produced exceptionally high levels of the enzyme dihydrofolate reductase (EC 1.5.1.3) in 6 h of batch fermentation. The culture had markedly improved performance under chemostat culture conditions in terms of enzyme yield and output. Temperature, pH, dilution rates, and nutrient composition were optimized under chemostat culture conditions. A maximum enzyme yield of 10,360 U l-1 and a specific activity of 22.84 U mg-1 were obtained under chemostat conditions at pH 7.0, temperature 37 degrees C, and dilution rate 0.2 h-1, using media containing 1.0 and 0.6% (w/v) dextrose and yeast extract, respectively. The culture's performance and enzyme yields in chemostat and the feasibility of large-scale production are discussed.

Bacteriological Techniques↗
PubMed1990

The inflammatory cervical smear: a study in general practice.

This study set out to determine whether the term 'inflammatory' in a cervical smear report implies underlying infection or whether it could be masking cancerous or precancerous changes. Of 826 smears taken in one practice over one year, 42 demonstrated some degree of inflammatory change. Thirty four of these women presented for swabs and almost half (47%) had a microbiologically proven infection. This group was further subdivided, and of those whose smears were reported as simple 'inflammation', just over one third (35%) were infected but of those whose smears were reported as 'severe inflammation', over two thirds were infected (73%). The commonest organisms isolated were Gardnerella vaginalis and Candida albicans. It would therefore appear to be worthwhile to treat patients who report severe inflammation with metronidazole and with anti-fungal pessaries before the smear is repeated. Following treatment two women went on to show dyskaryosis within five months. On colposcopy one of these women was found to have invasive cervical squamous cell carcinoma. It is concluded that whether women with inflammatory smears are treated or not, it is mandatory to repeat the smear, ideally within five months.

Adult↗
PubMed1987

The relationship between lysosomal enzyme release and protein phosphorylation in human monocytes stimulated by phorbol esters and opsonized zymosan.

Since it was established that phorbol esters bind to and activate protein kinase C, a proposed mechanism of action for these compounds has been the phosphorylation of specific protein substrates (Niedel, J. E., Kuhn, L. J., and Vandenbark, G. R. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 36-40; Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y. (1982) J. Biol. Chem. 257, 7847-7851). To better understand this proposed relationship, we investigated the ability of a series of phorbol esters to elicit lysosomal enzyme release (LER) and specific substrate phosphorylation in human monocytes. In this system, phorbol 12-myristate 13-acetate stimulated the secretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase in both a time- and concentration-dependent manner. Furthermore, the ability of a series of phorbol esters to stimulate LER was characterized and found to be in good agreement with the relative order of these compounds to stimulate the phosphorylation of four endogenous protein substrates. Phorbol ester-stimulated protein phosphorylation was examined in intact cell preparations and found to be concentration and structure-dependent. The phosphoproteins (pp) were designated pp28, pp55, pp61, and pp66 corresponding to their molecular masses in kilodaltons. These findings are consistent with the hypothesis that phorbol ester-mediated effects are the result of protein kinase C activation and subsequent protein phosphorylation. Finally, opsonized zymosan was found to elicit a concentration-dependent stimulation of N-acetyl-beta-D-glucosaminidase release similar in magnitude and time course to phorbol ester-stimulated LER. Opsonized zymosan also stimulated the phosphorylation of two phosphoproteins (pp61 and pp66) in a concentration-dependent manner. Specific phosphorylation of pp61 and pp66 by both secretagogues, phorbol 12-myristate 13-acetate and opsonized zymosan, suggests these two proteins may be key to the functional response of LER in human monocytes.

Acetylglucosaminidase↗
PubMed1985

The imaging revolution and radiation oncology: use of CT, ultrasound, and NMR for localization, treatment planning and treatment delivery.

The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This has forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume. This increase in precision and accuracy will presumably improve the results of radiation therapy.

Breast Neoplasms↗
PubMed1983

Dose to lung in primary breast irradiation.

Using anatomic data derived from computerized tomography (CT) scans of the torso, the volume of lung irradiated during primary breast treatment has been measured for a variety of irradiation techniques. Two-field tangential plans which are angled into lung to treat also the internal mammary nodes have been compared to three-field plans which include a separate internal mammary field (IMF). The volume of lung achieving high dose (greater than 3000 rad) is similar in both techniques when photons only are used. Electron beam treatment of the IMF is successful in lowering the lung dose. Additional treatment plans that angle the IMF parallel to the tangential fields may offer some theoretical advantage.

Breast Neoplasms↗