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Biomedical subjects

P A Watson

Publications and source records attributed to P A Watson.

At least 19 recordsLinked to original sources
PubMed2001

Role of cyclin-dependent kinase inhibitors in the growth arrest at senescence in human prostate epithelial and uroepithelial cells.

Cellular senescence has been proposed to be an in vitro and in vivo block that cells must overcome in order to immortalize and become tumorigenic. To characterize these pathways, we focused on changes in the cyclin-dependent kinase inhibitors and their binding partners that underlie the cell cycle arrest at senescence. As a model, we utilized normal human prostate epithelial cell (HPEC) and human uroepithelial cell (HUC) cultures. After 30-40 population doublings cells became growth-arrested in G0/1 with a threefold decrease in Cdk2-associated activity, a point defined as pre-senescence. Temporally following this growth arrest, the cells develop a senescence morphology and express senescence-associated beta-galactosidase (SA-beta-gal). Levels of p16(INK4a) and p57(KIP2) rise in HUCs during progressive passages, whereas only p16 increases in HPEC cultures. The induced expression of p57, similar to p16, produces a senescent-like phenotype. pRB, cyclin D, p19(INK4d) and p27(KIP1) decrease in both cell types. We find that p53, p21(CIP1) and p15(INK4b) are transiently elevated in HPECs and HUCs at the pre-senescent growth arrest, then return to low proliferating levels at terminal senescence. Analysis of p53, p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tumorigenic HPV16 E6 and E7 prostate lines and in tumorigenic prostate cancer cells. These results indicate: (i) the existence of a subset of growth inhibiting genes elevated at the onset of the senescence, (ii) a distinct class of genes involved in the maintenance of senescence, and (iii) the frequent inactivation of these pathways during immortalization.

Adult↗
PubMed2001

cAMP response element-binding protein content is a molecular determinant of smooth muscle cell proliferation and migration.

We hypothesized that cAMP response element-binding protein (CREB) could function as a molecular determinant of smooth muscle cell fate. In arterial sections from the systemic and pulmonary circulation, CREB content was high in proliferation-resistant medial subpopulations of smooth muscle cells and low in proliferation-prone regions. In vessels from neonatal calves exposed to chronic hypoxia, CREB content was depleted and smooth muscle cell (SMC) proliferation was accelerated. Induction of quiescence by serum deprivation in culture led to increased CREB content. Highly proliferative SMC in culture were observed to have low CREB content. Exposure to proliferative stimuli such as hypoxia or platelet-derived growth factor decreased SMC CREB content. Assessment of CREB gene transcription by nuclear run-on analysis and transcription from a CREB promoter-luciferase construct indicate that CREB levels in SMC are in part controlled at the level of transcription. Overexpression of wild type or constitutively active CREB in primary cultures of SMC arrested cell cycle progression. Additionally, expression of constitutively active CREB decreased both proliferation and chemokinesis. Consistent with these functional properties, active CREB decreased the expression of multiple cell cycle regulatory genes, as well as genes encoding growth factors, growth factor receptors, and cytokines. Our data suggest a unique mode of cellular phenotype determination at the level of the nuclear content of CREB.

Animals↗
PubMed2001

Diabetes-related changes in cAMP response element-binding protein content enhance smooth muscle cell proliferation and migration.

We hypothesized that diabetes and glucose-induced reactive oxygen species lead to depletion of cAMP response element-binding protein (CREB) content in the vasculature. In primary cultures of smooth muscle cells (SMC) high medium glucose decreased CREB function but increased SMC chemokinesis and entry into the cell cycle. These effects were blocked by pretreatment with the antioxidants. High glucose increased intracellular reactive oxygen species detected by CM-H(2)DCFA. SMC exposed to oxidative stress (H(2)O(2)) demonstrated a 3.5-fold increase in chemokinesis (p < 0.05) and accelerated entry into cell cycle, accompanied by a significant decrease in CREB content. Chronic oxidative challenge similar to the microenvironment in diabetes (glucose oxidase treatment) decreases CREB content (40-50%). Adenoviral-mediated expression of constitutively active CREB abolished the increase in chemokinesis and cell cycle progression induced by either high glucose or oxidative stress. Analysis of vessels from insulin resistant or diabetic animals indicates that CREB content is decreased in the vascular stroma. Treatment of insulin-resistant animals with the insulin sensitizer rosiglitazone restores vessel wall CREB content toward that observed in normal animals. In summary, high glucose and oxidative stress decrease SMC CREB content increase chemokinesis and entry into the cell cycle, which is blocked by antioxidants or restoration of CREB content. Thus, decreased vascular CREB content could be one of the molecular mechanisms leading to increased atherosclerosis in diabetes.

Animals↗
PubMed2001

Gas chromatography-mass spectrometry method for the simultaneous determination of wood extractive compounds in quaking aspen.

We have developed a rapid gas chromatography-mass spectrometry (GC-MS) method for the detailed compositional analysis of 70 underivatized wood extractive components present in quaking aspen (Populus tremuloides Michx.). Forty-four compounds were unequivocally identified by retention time and mass spectral comparison with standards. An additional 26 chromatographic peaks were assigned to broad chemical classes using retention time and mass spectra features. The results were compared to the respective tert.-butyldimethylsilyl derivatized wood extractives profile, and it was determined that derivatization was unnecessary for the GC-MS analysis of the target compounds.

Gas Chromatography-Mass Spectrometry↗
PubMed2001

Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial.

BACKGROUND: A totally transoral outpatient procedure for the treatment of GERD would be appealing. METHODS: A multicenter trial was initiated that included 64 patients with GERD treated with an endoscopic suturing device. Inclusion criteria were 3 or more heartburn episodes per week while not taking medication, dependency on antisecretory medicine, and documented acid reflux by pH monitoring. Exclusion criteria were dysphagia, grade 3 or 4 esophagitis, obesity, and hiatus hernia greater than 2 cm in length. Patients underwent manometry, endoscopy, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patients were randomized to a linear or circumferential plication configuration. Adverse procedural events were recorded. RESULTS: Mean 6-month symptom score changes demonstrated procedural efficacy. Heartburn severity and frequency as well as regurgitation all improved (p > 0.0001 for each). Twenty-four-hour pH monitoring showed improvement in number of episodes below pH of 4 at 3 and 6 months (p < 0.0007 and 0.0002) and percentage of total time the pH was less than 4 at 6 months (p < 0.011). Plication configuration did not affect symptoms or pH monitoring results. One patient had a self-contained suture perforation that was successfully treated with antibiotics. CONCLUSION: Endoscopic gastroplasty is safe. It is associated with reduced symptoms and medication use at 6 month follow-up in patients with uncomplicated GERD.

Gastroesophageal Reflux↗
PubMed1999

Adhesion of bonded orthodontic attachments to dental amalgam: In vitro study.

Bonding orthodontic attachments to molars is difficult in the presence of extensive buccal amalgam restorations. The purposes of this study were (1) to examine different amalgam surface preparations, (2) to examine properties of adhesive cements to amalgam, (3) to determine the most shear-resistant bonding technique and (4) to discuss whether these shear bond strengths were of adequate magnitude to be of clinical acceptability. The sample consisted of 108 standardized amalgam cylinders divided into 9 groups of 12 based on surface treatment technique and resin type. SPEED brackets (Strite Industries, Cambridge, Ontario) were bonded to amalgam surfaces that were either polished, sandblasted with 50 microm aluminium oxide, or chemically corroded. Adhesives used were Phase II (Reliance Orthodontic Products Inc, Itasca, Ill), Panavia EX (J Morita USA Inc, Tustin, Calif), or C & B Metabond (Parkell, Farmingdale, NY). After thermocycling from 10 degrees C to 50 degrees C 10,000 times, all samples were tested for shear bond strength with the Universal Testing Machine (Instron Corporation, Canton, Mass). The results show significantly higher bond strengths for all of the resin systems when sandblasting of the amalgam surface is used (P <.0001). Only Panavia EX bonded strongly to polished samples, suggesting the presence of a chemical bond. Laboratory acceptable bond strengths to amalgam are possible. The surface characteristics of the amalgam appear to be more influential in the strength of the bond than does the nature of the resin.

Acid Etching, Dental↗
PubMed1999

Entrapment of the index flexor digitorum profundus tendon after fracture of both forearm bones in a child.

Entrapment of the index FDP tendon in a radius fracture callus occurred after fracture of both forearm bones in a 4-year-old boy. Surgical release of the FDP tendon, three months after fracture, resulted in normal index finger motion. This clinical problem can be avoided by a detailed physical examination of children with forearm fractures, verifying full passive range-of-motion of the hand after cast immobilization. Prompt supervised active range-of-motion should be done to prevent adhesions at the fracture site.

Child, Preschool↗
PubMed1998

Comparison of a rapid dipstick test and thick blood films for detecting parasites of plasmodium falciparum used under typical conditions at a semi-rural hospital in Cote d'Ivoire.

This prospective study compares a rapid dipstick test (ParaSight-F) with thick blood films for the detection of parasites of P falciparum, under 'typical' conditions and constraints to be found in a semi-rural hospital in a tropical developing country in Africa. Eighty-two samples were tested using the two techniques and found to concur in 95.1% of cases. However, in four of the samples the results differed. The thick blood films of 60 samples were later re-read by a local reference laboratory. Of these 98.3% were in agreement with the reading performed at the hospital. Only one of the 60 slides differed. The rapid dipstick test proved to be both easy to use and free from many of the usual constraints such as a need for formally trained or experienced laboratory staff, laboratory equipment, and reliable water and electricity supplies. In an holoendemic area for P falciparum transmission, it would appear to be eminently suitable, in technical terms and ease of handling as well as on the basis of rapid results, for wider distribution within this region. Its main drawback remains financial.

Adolescent↗
PubMed1998

Modifications to the National Dental Examining Board of Canada's certification process.

Following a lengthy and intense consultation with stakeholders, and an analysis of the present certification process, the National Dental Examining Board of Canada (NDEB) and the 10 provincial licensing authorities recently approved major changes to the certification process for dental licensure in Canada. As of January 1997, graduates of dental programs accredited by the American Dental Association's Commission on Dental Accreditation (ADA Commission) must complete successfully the same examinations as graduates of programs accredited by the Commission on Dental Accreditation of Canada (CDAC) to be licensed to practice in Canada. In addition, NDEB's examination system for graduates of dental programs that are not accredited by CDAC or the ADA Commission (i.e. international programs) will be discontinued on December 31, 1999. As of January 1, 2000, graduates of non-accredited programs will be required to complete a CDAC accredited, university-based qualifying program to be eligible to participate in the same certification process as graduates of ADA Commission and CDAC accredited dental programs.

Accreditation↗
PubMed1998

The Endopore implant-enhanced osseointegration with a sintered porous-surfaced design.

The Endopore implant provides a novel method for reliable fixation of endosseous dental implants within the bone. Through the use of a porous-surfaced zone formed by sintering Ti alloy particles of the appropriate size and under appropriate processing conditions to a sold Ti alloy core of desired shape (tapered truncated cone), an implant is now available that can be placed using a relatively simple surgical procedure using either surgical burs or hand osteotomes. Of even greater value is the suitability of this implant design for treatment of cases that because of minimal bone height cannot be treated routinely using other currently-available implants. The high success rates experienced with significantly shorter implant lengths compared with other designs indicate the appropriateness of this system for difficult-to-treat cases. The Endopore system represents the next generation of endosseous dental implants characterized by uncomplicated and reliable treatment for a wider range of dentally-compromised patients. Its history is founded on extensive and fully-documented research at the human preclinical stage as well as human use experiences. The results during the past nine years have confirmed the high expectations that those early studies suggested.

Dental Implantation, Endosseous↗
PubMed1997

Isozyme-dependent sensitivity of adenylyl cyclases to P-site-mediated inhibition by adenine nucleosides and nucleoside 3'-polyphosphates.

Recombinant adenylyl cyclase isozyme Types I, II, VI, VII, and three splice variants of Type VIII were compared for their sensitivity to P-site-mediated inhibition by several adenine nucleoside derivatives and by the family of recently synthesized adenine nucleoside 3'-polyphosphates (Désaubry, L., Shoshani, I., and Johnson, R. A. (1996) J. Biol. Chem. 271, 14028-14034). Inhibitory potencies were dependent on isozyme type, the mode of activation of the respective isozymes, and on P-site ligand. For the nucleoside derivatives potency typically followed the order 2',5'-dideoxyadenosine (2',5'-ddAdo) > beta-adenosine > 9-(cyclopentyl)-adenine (9-CP-Ade) >/= 9-(tetrahydrofuryl)-adenine (9-THF-Ade; SQ 22,536), with the exception of Type II adenylyl cyclase, which was essentially insensitive to inhibition by 9-CP-Ade. For the adenine nucleoside 3'-polyphosphates inhibitory potency followed the order Ado < 2'-dAdo < 2',5'-ddAdo and 3'-mono- < 3'-di- < 3'-triphosphate. Differences in potency of these ligands were noted between isozymes. The most potent ligand was 2',5'-dd-3'-ATP with IC50 values of 40-300 nM. The data demonstrate isozyme selectivity for some ligands, suggesting the possibility of isozyme-selective inhibitors to take advantage of differences in P-site domains among adenylyl cyclase isozymes. Differential expression of adenylyl cyclase isozymes may dictate the physiological sensitivity and hence importance of this regulatory mechanism in different cells or tissues.

Adenosine↗
PubMed1997

Septic arthritis caused by chronic osteomyelitis.

We have treated four cases of previously quiescent osteomyelitis which presented as septic arthritis in an adjacent joint. The osteomyelitic focus was in the bone proximal to the involved joints (zero to ten centimeters above the joint line). Based on the presenting history, physical findings, laboratory tests and cultures of joint fluids, the joint sepsis was low grade in all patients which led to delays in diagnosis and treatment. Aggressive surgical debridement of both bone and joint, followed by a prolonged course of antibiotics led to resolution in all patients. A high index of suspicion combined with adequate radiographs of the surrounding bones should lead to the appropriate diagnosis and treatment.

Adult↗
PubMed1996

Initial healing in the dog of submerged versus non-submerged porous-coated endosseous dental implants.

It has previously been reported that porous-coated root form endosseous dental implants, became well integrated when used in the traditional 2-stage surgical approach. In this study, the placement of the implant in a 1-stage (non-submerged) technique was to be explored. Implants were placed in the mandibles of dogs, and 2 designs were used differing only in that one (experimental) had a 3-mm transgingival extension, permitting it to be exposed to the oral cavity from the outset. 12 (3 per animal) non-submerged implants were placed on 1 side of 4 beagle dogs and 12 control (submerged) implants were placed contralaterally. All implants were allowed to heal for 6 weeks, after which histological preparations were made. 2 of 12 non-submerged implants were lost due to post-operative complications; otherwise, all implants healed uneventfully. Histomorphometric analysis revealed bone-implant contact, as assessed by absolute bone contact (ABC) and contact length fraction (CLF), to be greater for the submerged design, suggesting that bone healing may be delayed with the non-submerged approach. As well, at this early stage of healing, for both implant designs, ABC and CLF were significantly greater on proximal than on buccal and lingual aspects.

Alloys↗
PubMed1996

Periodontal parameters around porous-coated dental implants after 3 to 4 years supporting overdentures.

In this study, an assessment using modified periodontal indices was done on a group of 48 fully edentulous patients who had each been treated with 3 porous-coated (EndoPore) dental implants and a mandibular overdenture. Parameters assessed included plaque index (PI), sulcular bleeding index (SBI), pocket probing depth (PD), probing attachment level (PAL) and mobility (M) using a Periotest device. At the time of the assessment, all of the patients had passed 3 years of continuous function while 26 had passed 4 years. Approximately 50% of implant surfaces were plaque-free while 79% of surfaces showed no bleeding upon probing. There was no correlation between PI and SBI. The mean PD was 3.1 mm with 64% of sites < or = 3.5 mm. Mobility measurements taken with the Periotest device gave a mean PTV of (-4.35) with 96% of measurements (-0.5). No significant correlations were found between mobility and either PAL or implant length.

Analysis of Variance↗
PubMed1996

Desmin gene expression in cardiac myocytes is responsive to contractile activity and stretch.

Experiments were performed to assess the ability of mechanical stimuli, experienced by ventricular cardiac myocytes during the progression of hypertrophic and dilated pathology, to increase the expression of desmin in cultured neonatal rat cardiac myocytes. Results indicate that both contractile activity and load due to passive stretch increase desmin content in neonatal rat cardiac myocytes through increased desmin gene transcription. Western blot analysis demonstrated that contraction induced a selective increase in desmin protein content in neonatal rat cardiac myocytes above increases observed in the content of total cellular protein. Northern blot analysis indicated that desmin mRNA content increased in response to contraction as well as to alpha-adrenergic stimulation. Desmin mRNA content also increased in cultured neonatal myocytes in response to stretch. Angiotensin II (ANG II) treatment of contracting neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocytes failed to increase desmin mRNA. This contraction-dependent responsiveness to ANG II is not a function of increases in the density or relative subtype composition of ANG II receptors. Treatment of contracting neonatal rat cardiac myocytes with actinomycin D prevented increases in desmin mRNA content, suggesting regulation of transcription of the desmin gene by contraction. Nuclear run-on experiments indicate that contraction. Nuclear run-on experiments indicate that contraction increases transcription of the desmin gene in cardiac myocytes. These results are consistent with the modulation of desmin gene expression secondarily to changes in the mechanical environment that occur in cardiac tissue undergoing dilation or hypertrophy.

Angiotensin II↗
PubMed1996

Contractile activity and passive stretch regulate tubulin mRNA and protein content in cardiac myocytes.

Accumulation of tubulin protein and an increased array of microtubules have been associated with contractile dysfunction in cardiac myocytes after pressure overload in vivo. Experiments were performed to assess the ability of mechanical stimuli experienced by ventricular cardiac myocytes during the progression of hypertrophic and dilated pathology to increase beta-tubulin production in cultured neonatal rat cardiac myocytes. Results indicate that both contractile activity and load due to passive stretch increase beta-tubulin protein content in neonatal rat cardiac myocytes through accumulation of beta-tubulin mRNA, which occurs without increased beta-tubulin gene transcription. Western blot analysis demonstrated that contraction resulted in the accumulation of beta-tubulin in neonatal rat cardiac myocytes above increases observed in the content of total cellular protein. Northern blot analysis indicated that beta-tubulin mRNA content increased in response to both stretch and contraction. alpha-Adrenergic agonists that lead to pathophysiological growth in cardiac myocytes also stimulated an increase in beta-tubulin mRNA content. Treatment of contracting neonatal cardiac myocytes with angiotensin II (ANG II) further increased beta-tubulin mRNA content, whereas ANG II treatment in arrested neonatal cardiac myocytes failed to increase beta-tubulin mRNA. Nuclear run-on experiments indicate that contraction stimulates beta-tubulin mRNA accumulation without an increase in beta-tubulin gene transcription. These results imply that tubulin production in cultured cardiac myocytes can be regulated directly by mechanical forces. In mechanically challenged hearts, the accumulation of beta-tubulin and the development of contractile dysfunction may be directly related to the mechanical forces imposed on the myocardium during the onset and progression of cardiovascular disease.

Animals↗
PubMed1996

Simplifying the treatment of edentulism: a new type of implant.

In this article, the authors describe the application of a new and unique root-form dental implant in a simplified approach to treating the completely edentulous mandible using an overdenture. The technique is supported by the results of a prospective clinical trial involving 52 patients that showed a three- to four-year success rate of 95 percent.

Alloys↗