PubMed Health⌕ Search

Biomedical subjects

R Gordon

Publications and source records attributed to R Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1999

2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.

Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the phenyl ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L-776,967) and the 3-pyridyl derivative 13 (L-784,506) are particularly interesting as potential antiinflammatory agents with reduced side-effect profiles. Both exhibit good oral bioavailability and are potent in standard models of pain, fever, and inflammation yet have a much reduced effect on the GI integrity of rats compared to standard nonsteroidal antiflammatory drugs.

Analgesics, Non-Narcotic↗
PubMed1999

Beyond micromachining: the potential of diatoms.

Diatoms are microscopic, single-celled algae that possess rigid cell walls (frustules) composed of amorphous silica. Depending on the species of diatom and the growth conditions, these frustules can display a wide range of different morphologies. It is possible to design and produce specific frustule morphologies that have potential applications in nanotechnology.

Biosensing Techniques↗
PubMed1999

Risk of cross-patient infection with clinical use of a needleless injector device.

BACKGROUND: Needleless injection devices use multiple-dose vials for the administration of local anesthetics to patients. There is a theoretic risk of iatrogenic infection associated with use of these devices. METHODS: This study used in vitro models to investigate the potential for transferring microbial pathogens among patients by using the Syrijet (Keystone Industries, Inc, Cherry Hill, NJ). Staphylococcus aureus and coagulase-negative staphylococci were used to determine whether patient skin flora could contaminate the instrument internal canal by postejection reverse flow and whether the staphylococci could survive on the ejection surface, in the internal canal, or in the anesthetic vial. RESULTS: The ejection surface was contaminated by firing the device while it was in contact with a contaminated surface. Postejection reverse flow drew contaminants into the device, and increased with ejection volume. Reverse flow did not reach the multidose vial, and staphylococci did not grow in the commercial anesthetic solution typically administered with the device. Surface, but not internal, contamination could be removed by swabbing with disinfectant. CONCLUSION: Although autoclaving is the only way to ensure sterilization of this device, frequent cleaning of the ejection surface during clinical use minimizes the risk of cross-patient bacterial transfer.

Cross Infection↗
PubMed1999

The axolotl as an animal model for the comparison of 3-D ultrasound with plain film radiography.

We assessed the usefulness of an animal model, the axolotl (Ambystoma mexicanum), in comparing 3-D ultrasound (3-D US) and plain film radiographs. Hindlimbs were amputated from 5 animals, at either the zeugopodial or stylopodial level, and each regenerating limb was imaged 16 times with 3-D US and 14 times with plain film X ray over 315 days. US images were acquired with a Siemens Sonoline Versa Pro and a 10-MHz linear array transducer. For 3-D US images, the probe was translated in a motor-driven linear stage while images were digitized. The regenerating tibia and fibula bones were detected on 3-D US an average of 37 days earlier than on plain film radiography, and regenerating phalangeal bones were detected on 3-D US an average of 18 days earlier. After 120 days, both imaging modalities consistently showed the bones. The average bone growth rates for the tibia and fibula were 0.019 +/- 0.001 mm/day and 0.019 +/- 0.001 mm/day, respectively.

Ambystoma↗
PubMed1999

Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts.

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.

Animals↗
PubMed1999

Relation of age of onset to the type and severity of child and adolescent conduct problems.

In a cross-sectional household sample of 9-through 17-year-old youths from 4 U.S. communities, youths with earlier ages of onset of conduct problems engaged in more conduct problems than youths with later ages of onset when current age and gender were controlled. Specifically, youths with earlier ages of onset were more likely to engage in several types of physical aggression, frequent lying, theft, and vandalism and were less likely to engage in only truancy. There also was an inverse relation between age of onset and level of functional impairment, mental health service use, and meeting diagnostic criteria for conduct disorder, attention-deficit hyperactivity disorder, and oppositional defiant disorder. Within the limits of cross-sectional data, these results support the hypothesis that key aspects of the heterogeneity of conduct problems among youths are related to the age of onset of conduct problems.

Adolescent↗
PubMed1999

Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation.

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan-induced paw oedema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw oedema) and high doses (hyperalgesia). COX-2 and prostaglandin E2 (PGE2) levels were measured by RT-PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a significant and parallel induction of both COX-2 and PGE2. This induction was significantly higher in hyperalgesia than in paw oedema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw oedema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw oedema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw oedema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.

Animals↗
PubMed1999

Increased severity of multifocal renal arterial fibromuscular dysplasia in smokers.

Renal arterial fibromuscular dysplasia (FMD) is a significant cause of renovascular hypertension, especially in younger females. Tobacco constituents have been shown to stimulate proliferation and synthetic activity of cultured human vascular smooth muscle cells. We examined the relationship between smoking and severity of FMD in a group of 50 subjects with the multifocal form of renal arterial FMD. A detailed smoking history was obtained by interview, clinical data at diagnosis of FMD were obtained from medical records, and angiograms were reviewed. Clinical and angiographic features were compared between smokers and non-smokers. Twenty-four subjects were smokers. At the time of diagnosis of FMD, smokers were of younger mean age than non-smokers (38.7 years vs 48.9 years, P < 0.01), had a shorter median history of hypertension (1.5 years vs 8.5 years, P < 0.05), and had a higher prevalence of unilateral renal atrophy (67% vs 27%, P < 0.01). The distribution of age at diagnosis of FMD was unimodal in non-smokers and bimodal, with a discrete group of younger subjects, in smokers. We conclude that cigarette smoking is associated with an earlier onset and increased severity of disease in a susceptible subgroup of patients predisposed to multifocal renal arterial FMD.

Adult↗
PubMed1999

Cortical motor potential alterations in chronic fatigue syndrome.

Premovement, sensory, and cognitive brain potentials were recorded from patients with Chronic Fatigue Syndrome (CFS) in four tasks: i) target detection, ii) short-term memory, iii) self-paced movement, and iv) expectancy and reaction time (CNV). Accuracy and reaction times (RTs) were recorded for tasks i, ii, and iv. Results from CFS patients were compared to a group of healthy normals. Reaction times were slower for CFS patients in target detection and significantly slower in the short-term memory task compared to normals. In target detection, the amplitude of a premovement readiness potential beginning several hundred milliseconds prior to stimulus onset was reduced in CFS, whereas the poststimulus sensory (N100) and cognitive brain potentials (P300) did not differ in amplitude or latency. In the memory task, a negative potential related to memory load was smaller in CFS than normals. The potentials to self-paced movements and to expectancy and RT (CNV) were not different between groups. The findings in CFS of slowed RTs and reduced premovement-related potentials suggest that central motor mechanisms accompanying motor response preparation were impaired in CFS for some tasks. In contrast, measures of neural processes related to both sensory encoding (N100) and to stimulus classification (P300) were normal in CFS.

Adult↗
PubMed1999

Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles.

The discoveries that cyclooxygenase (COX)-2 is an inducible form of COX involved in inflammation and that COX-1 is the major isoform responsible for the production of prostaglandins (PGs) in the gastrointestinal tract have provided a rationale for the development of specific COX-2 inhibitors as a new class of anti-inflammatory agents with improved gastrointestinal tolerability. In the present study, the preclinical pharmacological and biochemical profiles of rofecoxib [Vioxx, also known as MK-0966, 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone], an orally active COX-2 inhibitor, are described. Rofecoxib is a potent inhibitor of the COX-2-dependent production of PGE(2) in human osteosarcoma cells (IC(50) = 26 +/- 10 nM) and Chinese hamster ovary cells expressing human COX-2 (IC(50) = 18 +/- 7 nM) with a 1000-fold selectivity for the inhibition of COX-2 compared with the inhibition of COX-1 activity (IC(50) > 50 microM in U937 cells and IC(50) > 15 microM in Chinese hamster ovary cells expressing human COX-1). Rofecoxib is a time-dependent inhibitor of purified human recombinant COX-2 (IC(50) = 0.34 microM) but caused inhibition of purified human COX-1 in a non-time-dependent manner that could only be observed at a very low substrate concentration (IC(50) = 26 microM at 0.1 microM arachidonic acid concentration). In an in vitro human whole blood assay, rofecoxib selectively inhibited lipopolysaccharide-induced, COX-2-derived PGE(2) synthesis with an IC(50) value of 0.53 +/- 0.02 microM compared with an IC(50) value of 18.8 +/- 0.9 microM for the inhibition of COX-1-derived thromboxane B(2) synthesis after blood coagulation. Using the ratio of the COX-1 IC(50) values over the COX-2 IC(50) values in the human whole blood assay, selectivity ratios for the inhibition of COX-2 of 36, 6.6, 2, 3, and 0.4 were obtained for rofecoxib, celecoxib, meloxicam, diclofenac, and indomethacin, respectively. In several in vivo rodent models, rofecoxib is a potent inhibitor of carrageenan-induced paw edema (ID(50) = 1.5 mg/kg), carrageenan-induced paw hyperalgesia (ID(50) = 1.0 mg/kg), lipopolysaccharide-induced pyresis (ID(50) = 0.24 mg/kg), and adjuvant-induced arthritis (ID(50) = 0.74 mg/kg/day). Rofecoxib also has a protective effect on adjuvant-induced destruction of cartilage and bone structures in rats. In a (51)Cr excretion assay for detection of gastrointestinal integrity in either rats or squirrel monkeys, rofecoxib has no effect at doses up to 200 mg/kg/day for 5 days. Rofecoxib is a novel COX-2 inhibitor with a biochemical and pharmacological profile clearly distinct from that of current nonsteroidal anti-inflammatory drugs and represents a new therapeutic class of anti-inflammatory agents for the treatment of the symptoms of osteoarthritis and rheumatoid arthritis with improved gastrointestinal tolerability.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1998

Long-term prognostic value of exercise echocardiography compared with exercise 201Tl, ECG, and clinical variables in patients evaluated for coronary artery disease.

BACKGROUND: The accuracy of exercise echocardiography and 201Tl single photon emission computed tomography (SPECT) is similar in the diagnosis of coronary artery disease (CAD). However, comparative data on long-term prognosis are lacking. METHODS AND RESULTS: Clinical variables and exercise, echocardiographic, and 201Tl tomographic parameters were studied in 248 patients (age, 56+/-12 years [mean+/-SD]; 189 men) who underwent simultaneous treadmill exercise 201Tl SPECT and echocardiography. Follow-up was obtained in 225 patients (91%) at a mean of 3.7+/-2.0 years. A total of 64 cardiac events occurred. With the use of stepwise logistic regression, 4 models simulating clinical stress testing scenarios were evaluated in the prediction of all cardiac events, ischemic events, and/or cardiac death. The best clinical models were exercise echocardiography with exercise ECG and exercise 201Tl SPECT with exercise ECG. Both models were comparable in the prediction of cardiac events. For the exercise echocardiography model, exercise wall motion score index and induction of ischemia were the strongest predictors of events with ORs of 2.63 per unit increment (95% CI, 1. 34 to 5.17; P=0.005) and 4.1 (95% CI, 1.32 to 12.79; P=0.015), respectively. For the model with exercise 201Tl SPECT, the strongest predictor was ischemic perfusion defect (OR, 4.93; 95% CI, 1.72 to 14.08; P=0.003). The absence of ST changes during exercise decreased the risk of events. For the prediction of ischemic events and/or cardiac death, echocardiographic and 201Tl parameters were the only predictive variables. CONCLUSIONS: In patients evaluated for CAD, exercise echocardiography and 201Tl combined with ECG variables provide comparable prognostic information and can be used interchangeably for risk stratification.

Adult↗
PubMed1998

2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors.

A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.

Administration, Oral↗
PubMed1998

Control of cytoskeletal architecture by the src-suppressed C kinase substrate, SSeCKS.

Activation of protein kinase C (PKC) in many cell types results in cytoskeletal reorganization associated with cell proliferation. We previously described a new cell cycle-regulated myristylated PKC substrate, SSeCKS (pronounced essex), that interacts with the actin cytoskeleton [Lin et al., 1995, 1996]. SSeCKS shares significant homology with Gravin, which encodes kinase scaffolding functions for PKC and PKA [Nauert et al., 1997]. This article describes the cellular effects of ectopically expressing SSeCKS in untransformed NIH3T3 fibroblasts. Because the constitutive overexpression of SSeCKS is toxic [Lin et al., 1995], we developed cell lines with tetracycline (tet)-regulated SSeCKS expression. The induction of SSeCKS (removal of tet) caused significant cell flattening and the elaboration of an SSeCKS-associated cortical cytoskeletal matrix resistant to Triton X-100 extraction. Flattened cells were growth-arrested and marked by the formation of cellular projections and the temporary loss of actin stress fibers and vinculin-associated adhesion plaques. SSeCKS overexpression did not affect steady-state levels of actin, vinculin, or focal adhesion kinase (FAK) but did increase integrin-independent FAK tyrosine phosphorylation. Stress fiber loss was coincident with induced SSeCKS expression, strongly suggesting a direct effect. Cytochalasin, and to a lesser extent nocodazole, inhibited SSeCKS-induced cell flattening, however, only cytochalasin affected the shape of pre-flattened cells, suggesting a greater dependence on microfilaments, rather than microtubules. By contrast, only nocodazole caused retraction of the filopodia-like processes. These data indicate a role for SSeCKS in modulating both cytoskeletal and signaling pathways. Thus, we propose to expand SSeCKS scaffolding functions to include the ability to control actin-based cytoskeletal architecture, as well as mitogenic signal pathways.

3T3 Cells↗
PubMed1998

Combining various projection access schemes with the algebraic reconstruction technique for low-contrast detection in computed tomography.

We separately applied three different projection access orders (the multilevel scheme (MLS), the sequence access scheme (SAS) and the random permutation scheme (RPS)) to the algebraic reconstruction technique (ART) in an attempt to improve low-contrast object detection in computed tomography (CT). We used both simulated (from various numbers of projections of low-contrast and contrast detail phantoms) and actual data (from megavoltage portal CT) during our study. When coupled with ART, SAS and RPS led to poor low-contrast detection and required multiple iterations for convergence. In contrast, one-iteration MLS yielded the most uniform reconstructions with the highest contrast-to-noise ratios. Therefore, MLS-ART provides the highest dose efficiency of all current reconstruction techniques for imaging low-contrast objects from a small number of projections.

Algorithms↗
PubMed1998

Risk perceptions of offshore workers on UK oil and gas platforms.

Knowledge of the workforce's risk perceptions and attitudes to safety is necessary for the development of a safety culture, where each person accepts responsibility for working safely. The ACSNI Human Factors report stresses the importance of assessing workforce perceptions of risk to achieve a proper safety culture. Risk perception research has been criticized for insufficient analysis of the causal relationships between risk factors and perceived risk. The present study reports some of the factors which predicted risk perception in a sample of 622 employees from six UKCS offshore oil installations who completed a 15-section questionnaire. This paper focuses on the accuracy of workers' risk perceptions and what underlying factors predict the perception of personal risk from both major and minor hazards.

Accidents, Occupational↗
PubMed1998

Neotropical echinococcosis in Suriname: Echinococcus oligarthrus in the orbit and Echinococcus vogeli in the abdomen.

This paper reports two cases of neotropical echinococcosis caused by Echinococcus oligarthrus and E. vogeli, neither of which has been reported from Suriname. Case 1, a six-year-old boy, presented a 15 x 25 mm retro-ocular cystic tumor (observed by ultrasound, computed tomography scan, and magnetic resonance imaging) causing exophthalmia, chemosis, palpebral ptosis, and blindness of the left eye. Of two tentative diagnoses, Echinococcus cyst or dermoid tumor, the former was shown to be correct at surgery when a clear liquid and detached protoscoleces were aspirated. Rostellar hooks of the protoscolex were characteristic of E. oligarthrus. Case 2, a 41-year-old man, had polycystic masses excised from the liver and abdomen. A presurgery diagnosis of E. vogeli infection was made due to calcifications seen in the lesions, positive serology, residence of the patient in the tropical forest, and later by the size and shape of rostellar hooks. The presence of these two parasites in one of the former Guianas is not surprising; both species are endemic in tropical forest in Central and South America wherever people have not exterminated wild canids, especially the bush dog, (Speothos venaticus), and felids (wild cats of several species), along with pacas, agoutis, and other rodents that serve as intermediate host of these two cestodes. Eighty-six cases of polycystic echinococcosis are known in people from 11 countries from Nicaragua to Argentina: 32 due to E. vogeli, three to E. oligarthrus, and 51 for which determination of the species was not possible because the hooks of the protoscolex were not found or described. Research to elucidate aspects of transmission of E. vogeli and E. oligarthrus is of practical importance for defining measures for preventing the severe and frequently fatal illnesses caused by these two cestodes.

Abdomen↗