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Biomedical subjects

P M Gordon

Publications and source records attributed to P M Gordon.

At least 19 recordsLinked to original sources
PubMed2002

Generalized pustular and erythrodermic psoriasis associated with bupropion treatment.

Severe drug eruptions may cause diagnostic and therapeutic difficulty when they mimic or provoke endogenous patterns of dermatosis. We report three patients with known psoriasis in whom use of bupropion (Zyban), prescribed to assist with cessation of smoking, led to severe pustular or erythrodermic exacerbation of psoriasis within 3-5 weeks. All patients were systemically unwell and required hospitalization to control the disease flare.

Adult↗
PubMed2001

The complete genome of the crenarchaeon Sulfolobus solfataricus P2.

The genome of the crenarchaeon Sulfolobus solfataricus P2 contains 2,992,245 bp on a single chromosome and encodes 2,977 proteins and many RNAs. One-third of the encoded proteins have no detectable homologs in other sequenced genomes. Moreover, 40% appear to be archaeal-specific, and only 12% and 2.3% are shared exclusively with bacteria and eukarya, respectively. The genome shows a high level of plasticity with 200 diverse insertion sequence elements, many putative nonautonomous mobile elements, and evidence of integrase-mediated insertion events. There are also long clusters of regularly spaced tandem repeats. Different transfer systems are used for the uptake of inorganic and organic solutes, and a wealth of intracellular and extracellular proteases, sugar, and sulfur metabolizing enzymes are encoded, as well as enzymes of the central metabolic pathways and motility proteins. The major metabolic electron carrier is not NADH as in bacteria and eukarya but probably ferredoxin. The essential components required for DNA replication, DNA repair and recombination, the cell cycle, transcriptional initiation and translation, but not DNA folding, show a strong eukaryal character with many archaeal-specific features. The results illustrate major differences between crenarchaea and euryarchaea, especially for their DNA replication mechanism and cell cycle processes and their translational apparatus.

Cell Cycle Proteins↗
PubMed2001

Metal ion coordination by the AGC triad in domain 5 contributes to group II intron catalysis.

Group II introns require numerous divalent metal ions for folding and catalysis. However, because little information about individual metal ions exists, elucidating their ligands, functional roles and relationships to each other remains challenging. Here we provide evidence that an essential motif at the catalytic center of the group II intron, the AGC triad within domain 5 (D5), provides a ligand for a crucial metal ion. Sulfur substitution of the pro-Sp oxygen of the adenosine strongly disrupts D5 binding to a substrate consisting of an exon and domains 1-3 of the intron (exD123). Cd2+ rescues this effect by enabling the sulfur-modified D5 to bind to exD123 with wild type affinity and catalyze 5'-splice site cleavage. This switch in metal specificity implies that a metal ion interacts with D5 to mediate packing interactions with D123. This new D5 metal ion rescues the disruption of D5 binding and catalysis with a thermodynamic signature different from that of the metal ion that stabilizes the leaving group during the first step of splicing, suggesting the existence of two distinct metal ions.

Base Sequence↗
PubMed2000

Kinetic characterization of the second step of group II intron splicing: role of metal ions and the cleavage site 2'-OH in catalysis.

The ai5gamma group II intron from yeast excises itself from precursor transcripts in the absence of proteins. When a shortened form of the intron containing all but the 3'-terminal six nucleotides is incubated with an exon 1 oligonucleotide and a 3' splice site oligonucleotide, a nucleotidyl transfer reaction occurs that mimics the second step of splicing. As this tripartite reaction provides a means to identify important functional groups in 3' splice site recognition and catalysis, we establish here a minimal kinetic framework and demonstrate that the chemical step is rate-limiting. We use this framework to characterize the metal ion specificity switch observed previously upon sulfur substitution of the 3'-oxygen leaving group and to elucidate by atomic mutagenesis the role of the neighboring 2'-OH in catalysis. The results suggest that both the 3'-oxygen leaving group and the neighboring 2'-OH are important ligands for metal ions in the transition state but not in the ground state and that the 2'-OH may play an additional role in transition state stabilization by donating a hydrogen bond. Metal specificity switch experiments combined with quantitative analysis show that the Mn(2+) that interacts with the leaving group binds to the ribozyme with the same affinity as the metal ion that interacts with the neighboring 2'-OH, raising the possibility that a single metal ion mediates interactions with the 2'- and 3'-oxygen atoms at the 3' splice site.

Binding Sites↗
PubMed2000

The quantity and quality of physical activity among those trying to lose weight.

BACKGROUND: Regular exercise to elicit caloric expenditure is an important component for achieving weight loss. The Healthy People 2000 objectives recommend regular sustained physical activity lasting 30 minutes, five days per week (Objective 1.3) particularly for weight loss. Moreover, this recommendation has been restated for weight loss and overall health benefits in the Centers for Disease Control and Prevention / American College of Sports Medicine (CDC/ACSM) statement and Surgeon General's Report (SGR) on Physical ActivitY and Health. Thus, we sought to identify the relative quality, and quantity of physical activity among people trying to lose weight. DESIGN: Cross-sectional self-reported data from the West Virginia Behavioral Risk Factor Surveillance System (BRFSS) were used. The BRFSS is a state-based telephone survey of adults that uses a multistage cluster design based on the Waksberg method of random-digit dialing. Data froM 2769 men and 4490 women were obtained from the 1992, 1994, and 1996 surveys. RESULTS: Half (49.6%) of individuals trying to lose weight did not engage in any physical activity. Further, only 15% of respondents trying to lose weight reported exercising regularly. Nevertheless, those trying to lose weight were more likely (OR [odds ratio] = 1.3; 95% CI [confidence interval], 1.14, 1.51, p < 0.001) to exercise regularly than those not trying to lose weight. In particular, women trying to lose weight were significantly more likely (OR = 1.45; 95% CI, 1.22,1.74, p < 0.001) to exercise regularly than women not trying to lose weight. Conversely, men trying to lose weight were no more likely to exercise regularly (p = .23) than men not trying to lose weight. Among respondents who were using exercise for weight loss, only 14.7% were expending > or =1000 kcal/week and 18.2% were expending > or =500 kcal/week. Weekly expenditure rates of > or =1000 kcal/week were more likely to occur among men (17%) than women (13.8%), in younger age groups, and among those with higher educational attainment. CONCLUSION: These data suggest that while certain individuals trying to lose weight are more likely to engage in regular physical activity, most persons trying to lose weight have not adopted regular physical activity as part of their weight loss practice. These results suggest that public health efforts to effectively integrate physical activity into weight control practices of West Virginians have been minimally successful.

Adult↗
PubMed2000

Metal ion catalysis during the exon-ligation step of nuclear pre-mRNA splicing: extending the parallels between the spliceosome and group II introns.

Mechanistic analyses of nuclear pre-mRNA splicing by the spliceosome and group II intron self-splicing provide insight into both the catalytic strategies of splicing and the evolutionary relationships between the different splicing systems. We previously showed that 3'-sulfur substitution at the 3' splice site of a nuclear pre-mRNA has no effect on splicing. We now report that 3'-sulfur substitution at the 3' splice site of a nuclear pre-mRNA causes a switch in metal specificity when the second step of splicing is monitored using a bimolecular exon-ligation assay. This suggests that the spliceosome uses a catalytic metal ion to stabilize the 3'-oxyanion leaving group during the second step of splicing, as shown previously for the first step. The lack of a metal-specificity switch under cis splicing conditions indicates that a rate-limiting conformational change between the two steps of splicing may mask the subsequent chemical step and the metal-specificity switch. As the group II intron, a true ribozyme, uses identical catalytic strategies for splicing, our results strengthen the argument that the spliceosome is an RNA catalyst that shares a common molecular ancestor with group II introns.

Adenoviridae↗
PubMed2000

Basal cell carcinoma: are early appointments justifiable?

In the U.K., patients with suspected skin tumours are usually referred from a general practitioner to a hospital-based dermatologist for treatment. The urgency of such referrals is currently a topic of political importance. We have studied case record data from 162 patients with basal cell carcinoma (BCC) to establish the relevance of referrals routinely being considered urgent. At presentation, mean tumour size (maximum dimension) was 7. 4 mm (median 10) and mean duration of BCC was 20.5 months (median 12). There was no correlation (all P > 0.05) between tumour size and patient age (r = 0.1325), tumour size and duration (r = 0.4433), or tumour size and interval between referral and hospital consultation (r = 0.0695). If the slow growth rate of the average BCC is assumed to be linear, a reduction in referral interval from the mean value of 10.7 weeks in our patients down to the U.K. government target of 2 weeks would equate to a size difference in BCC of 0.7 mm, which is not therapeutically significant. Individual BCCs with rapid growth or other features of concern may require urgent referral, but evidence from our patients and from other studies is that this is not routinely necessary.

Adult↗
PubMed1999

Metal ion catalysis during group II intron self-splicing: parallels with the spliceosome.

The identical reaction pathway executed by the spliceosome and self-splicing group II intron ribozymes has prompted the idea that both may be derived from a common molecular ancestor. The minimal sequence and structural similarities between group II introns and the spliceosomal small nuclear RNAs, however, have left this proposal in question. Mechanistic comparisons between group II self-splicing introns and the spliceosome are therefore important in determining whether these two splicing machineries may be related. Here we show that 3'-sulfur substitution at the 5' splice site of a group II intron causes a metal specificity switch during the first step of splicing. In contrast, 3'-sulfur substitution has no significant effect on the metal specificity of the second step of cis-splicing. Isolation of the second step uncovers a metal specificity switch that is masked during the cis-splicing reaction. These results demonstrate that group II intron ribozymes are metalloenzymes that use a catalytic metal ion for leaving group stabilization during both steps of self-splicing. Furthermore, because 3'-sulfur substitution of a spliceosomal intron has precisely the same effects as were observed during cis-splicing of the group II intron, these results provide striking parallels between the catalytic mechanisms employed by these two systems.

Allosteric Regulation↗
PubMed1999

A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis.

BACKGROUND: Although PUVA treatment of psoriasis is more effective than conventional or broad-band UVB phototherapy, two small studies have suggested that narrow-band or TL-01 phototherapy may have a therapeutic effect equal to PUVA. If confirmed, this would be of considerable importance as TL-01 therapy is likely to be considerably safer in the long term than PUVA. OBJECTIVE: The purpose of this study was to compare PUVA with narrow-band (TL-01) phototherapy in psoriasis. METHODS: We studied 100 patients with plaque-type psoriasis who were randomly allocated to twice-weekly treatment with PUVA or narrow-band UVB. RESULTS: Clearance of psoriasis was achieved in a significantly greater proportion of patients treated with PUVA (84%) than with TL-01 (63%) (P =.018), and with significantly fewer treatments (median number of treatments for clearance with PUVA, 16.7; with TL-01, 25.3; P =.001). Only 12% of those treated with TL-01 were clear of psoriasis 6 months after finishing treatment compared with 35% for PUVA (P =.002). CONCLUSION: When given twice weekly, PUVA is more effective for psoriasis than narrow-band UVB phototherapy.

Adult↗
PubMed1998

Phototesting prior to narrowband (TL-01) ultraviolet B phototherapy.

A device for phototesting patients prior to narrowband phototherapy is described. One hundred and fifty patients (130 with psoriasis and 20 with eczema) of skin types I-IV were phototested on the forearm and 22 on both forearm and back. The minimal erythema dose (MED) was judged visually 24 h after irradiation, and in those patients who were tested at two body sites, objective measurement of the erythema was made using a reflectance instrument. The MED values on the arm showed a fivefold range. There was no significant association between skin type and MED. The MED values on the arm were significantly higher than those measured on the back, although the differences were small in the majority of cases. No significant difference was found between the slopes of the dose-response curves measured on the arm and on the back.

Adolescent↗
PubMed1998

Effects of acute exercise on high density lipoprotein cholesterol and high density lipoprotein subfractions in moderately trained females.

Increases in high density lipoprotein cholesterol (HDL-C) levels have previously been reported after moderate exercise bouts lasting less than two hours in men. Little information exists, however, on HDL-C responses after moderate duration exercise in women. Post-exercise HDL-C modifications may appear differently in women because of higher baseline HDL-C concentrations and differences in lipolytic activity. To determine the influence of exercise on acute HDL-C responses in women, 12 trained premenopausal women (22 (4) years old; mean (SD)) who ran 24-48 km a week exercised on a motor driven treadmill at 75% VO2MAX until 3.34 MJ (800 kcal) were expended (72 (9) min). Subjects were all tested during the early follicular phase of their menstrual cycle. Fasting blood samples were obtained before exercise (baseline), immediately after (IPE), one hour after (1 h PE), 24 hours after (24 h PE), and 48 hours after (48 h PE) exercise. Plasma was analysed for HDL-C, HDL2-C, and HDL3-C. A significant increase in HDL-C was observed 48 h PE (p<0.05). HDL3-C increased IPE (p<0.01) but returned to baseline at 1 h PE. In contrast, HDL2-C was not significantly different from baseline at any time point. The rise in HDL-C, however, was attributed to an increase in both HDL2 and HDL3. Moreover, at 48 h PE, the increase in HDL-C correlated highly with changes in HDL2-C (r = 0.92). Thus it appears that exercise of moderate duration can elicit similar post-exercise increases in HDL-C in women to those previously reported in men. However, the changes in HDL subfractions leading to the rise in HDL-C may be different in women.

Adolescent↗
PubMed1998

Effect of different quantities of variable practice on acquisition, retention, and transfer of an applied motor skill.

This investigation examined the effect of manipulating different quantities of variable practice in the acquisition phase on the retention and transfer performance of a dart throw. Participants in the Specific condition practiced a total of 75 acquisition trials from a distance of 2.39 m. Participants in the Specific + Variable condition practiced a total of 75 acquisition trials with 25 trials from distances of 1.47 m, 2.39 m, and 3.30 m. Participants in the Specific + Varplus condition practiced a total of 75 acquisition trials with 15 trials from distances of 1.47 m, 1.93 m, 2.39 m, 2.84 m, and 3.30 m. Results of the one-way analysis of variance on the 24-hr. retention test from 2.39 m yielded no significant differences among practice conditions for mean radial error. A one-way analysis of variance on the 24-hr. transfer test from 3.76 m indicated that the Specific + Variable and Specific + Varplus conditions performed with significantly smaller mean radial error than the Specific condition. The results are discussed in regard to recent research and applicability to instructional settings.

Analysis of Variance↗
PubMed1996

Effects of exercise with varying energy expenditure on high-density lipoprotein-cholesterol.

To investigate the effect of varying energy expenditure on acute high-density lipoprotein-cholesterol (HDL-C) changes, 12 healthy endurance-trained men completed three- counterbalanced running trials at different energy expenditures: trial 1, 1690.3 (24.4) kJ [mean (SD)]; trial 2, 2529.1 (24.0) kJ; trial 3, 3384.3 (36.6) kJ, with exercise intensity at 75% of maximal oxygen consumption. For each trial, blood samples were collected at 24 h pre-exercise (24 h Pre), immediately post-exercise, 1 h post-exercise, 6 h post-exercise (6 h PE), and 24 h post-exercise (24 h PE). Plasma samples were analyzed for HDL-C, HDL2-C and HDL3-C subfractions, and triglycerides (TG). In addition, post-heparin plasma samples were analyzed at 24 h Pre, 6 h PE and 24 h PE for lipoprotein lipase activity (LPLA) and hepatic triglyceride lipase activity. All samples were corrected for plasma volume changes and compared to 24 h Pre (baseline). When trials were combined, an increase (P < 0.05) in HDL-C was observed 24 h PE, via an increase (P < 0.05) in HDL3-C. An increase (P < 0.05) in LPLA and decrease (P < 0.05) in TG at 24 h PE is suggested to be responsible for the increase in HDL3-C. In conclusion, no difference in HDL-C was observed among trials. However, when trials were combined, an increase in HDL-C was observed, suggesting that an energy expenditure of no greater than 3384 kJ is needed to promote favorable changes in HDL-C.

Adolescent↗
PubMed1996

Sensitivity to sternotomy wires may cause postoperative pruritus.

An eczematous eruption developed on the anterior chest of a 58-year-old woman with known nickel sensitivity after the insertion of nickel-containing sternotomy wires. Her wound was revised with removal of the wires to give immediate and sustained relief from the itch. The electron microscopy and parasternal biopsy histology demonstrating a sarcoidal reaction are discussed.

Dermatitis, Allergic Contact↗
PubMed1996

Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol.

delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects.

Animals↗