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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 325 records · Page 18Linked to original sources

Transcriptional regulation of an unusual trypsin-related protein expressed during insect metamorphosis.

The full-length cDNA for a trypsin-related protein expressed during larval-pupal metamorphosis was obtained. The encoded N-terminal half of the protein possessed similarity to trypsin proteases, including the correctly positioned histidine and aspartic acid members of the catalytic triad. However, the remainder of the encoded protein bore little resemblance to trypsin, and was altogether missing the canonical sequence containing the catalytic serine residue. The product of in vitro transcription/translation of the cDNA was a 28 kDa protein. Under normal conditions of a declining juvenile hormone titer, transcription of the mRNA as a proportion of total genomic transcription steadily increased for the first 3 days of the final stadium, but this increase was delayed and suppressed by maintenance of a high juvenile hormone titer. During the normal increase in transcription on day 3 of the final stadium, a sharp decline was observed in the steady-state abundance of the transcript, measured relative to abundance of the remaining mRNAs, suggesting that the stability of the message decreases after tissue commitment for a pupal molt.

Amino Acid Sequence↗

Intensity and direction dimensions of competitive state anxiety and relationships with performance.

This study examined relationships between intensity and direction dimensions of competitive state anxiety, and also relationships with beam performance in a sample of female gymnasts. The 48 gymnasts, whose ages ranged from 14 to 16 years, competed in a beam competition and were divided, via the median split technique, into poor performance and good performance groups. All the subjects completed a modified version of the Competitive State Anxiety Inventory-2 (CSAI-2) 10 min prior to performance. This inventory included the original intensity scale plus a direction scale in which subjects rated the degree to which the experienced intensity of each symptom was either facilitative of debilitative to subsequent beam performance. Analyses of variance showed no significant group differences on any of the CSAI-2 sub-component intensity scores, or on somatic anxiety and self-confidence direction scores. However, the good performance group reported their cognitive anxiety intensity as being more facilitating and less debilitating to performance than the poor performance group. Stepwise multiple-regression analyses showed that the only significant predictor of beam performance was self-confidence intensity. These findings support the proposal that sports performers' directional perceptions of their anxiety symptoms may provide further understanding of the competitive state anxiety response, and also emphasize the importance of self-confidence in predicting performance.

Adolescent↗

Intensity and frequency dimensions of competitive state anxiety.

This study reports a preliminary investigation of intensity and frequency of symptoms of competitive state anxiety. Forty-nine track and field athletes (27 males, 22 females) responded to a modified version of the Competitive State Anxiety Inventory-2 (CSAI-2) on four occasions during the period leading up to an important competition: 2 days, 1 day, 2 h and within 30 min of competing. The questionnaire included the existing CSAI-2 (intensity) scale as well as a frequency scale for each of the 27 items of the CSAI-2. The intensity and frequency dimensions of each of the CSAI-2-sub-scales were then compared between the four conditions by means of two-way analyses of variance (gender x time-to-competition). In the case of cognitive anxiety, time-to-event effects were observed for intensity and frequency for both males and females. The intensity of the response was significantly greater at the final stage of testing than it was 2 days before competition, while the frequency of the response increased progressively throughout the experimental period. This dissociative patterning for the cognitive anxiety dimensions is discussed in the light of Multidimensional Anxiety Theory predictions. For somatic anxiety, the time-to-event effects that emerged for intensity and frequency revealed that both values increased progressively as the time to compete neared, for both male and females. The results for self-confidence revealed no effects for intensity or frequency for either gender. The findings from structured follow-up interviews served to corroborate these quantitative findings by providing information that supported the conclusions drawn from the questionnaire data. In particular, the athletes reported that they experienced considerable increases in the frequency of intrusive anxiety cognitions. While these findings clearly need to be substantiated, they do provide evidence of the existence of an additional dimension of anxiety that may assist our understanding of this complex concept. The measurement of competitive state anxiety may benefit from this more detailed approach as opposed to the rather limited intensity-alone perspective.

Adult↗

A phase II trial of concomitant human interleukin-2 and interferon-alpha-2a in patients with disseminated malignant melanoma.

Interleukin-2 (IL-2) and alpha-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 10(6) U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-alpha-2a at a dose of 6 x 10(6) U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and alpha-interferon does not appear to be better than the single agents used alone in optimal dosage.

Adult↗

Yttrium synovectomy: a meta-analysis of the literature.

BACKGROUND: Yttrium synovectomy for chronic synovitis of the knee enjoys widespread usage in Australia with approximately 400 patients receiving yttrium-90 in 1991. Despite abundant anecdotal evidence of its efficacy there is a paucity of controlled trials and those that have been done have produced conflicting results and have been of insufficient sample size. AIMS: To critically and quantitatively evaluate the published English literature on comparative trials of yttrium-90 therapy for chronic synovitis of the knee. METHODS: The technique of meta-analysis was utilised. The literature search was carried out using the MeSH terms of synovectomy and knee; and yttrium. This was augmented by referring to reviews, current textbooks and back-references. Outcome measures varied between trials but could be grouped as treatment success. The Peto modification of Mantel and Haenszl was used for statistical pooling of data yielding a pooled odds ratio (OR). RESULTS: The literature search revealed ten controlled trials of which two were excluded from further analysis. Yttrium was superior to placebo (OR 2.42, 95% CI 1.02-5.73) but this result should be interpreted with caution due to possible publication bias. Yttrium was not superior to triamcinolone (OR 1.89, 95% CI 0.81-10.55) or other active modalities (OR 1.04, 95% CI 0.72-1.52). Further research comparing yttrium with other modalities is necessary to properly determine its place in rheumatological practice.

Anti-Inflammatory Agents↗

Hemorrhagic complications in a rapidly growing, congenital hemangiopericytoma.

A 3-week-old infant had a massive hemangioma-like vascular neoplasm that had enlarged rapidly since being noted at birth. Less than a day after this initial evaluation the tumor underwent spontaneous ulceration and the infant had a near-fatal hemorrhage. Histologically, the tumor was a spindle cell neoplasm most consistent with the diagnosis of congenital hemangiopericytoma. Local excision appears to have been curative after almost two years of follow-up. The case is instructive in pointing out the importance of considering nonhemangioma vascular neoplasms in the evaluation of newborns with vascular tumors.

Female↗

Contribution of water condensation in endotracheal tubes to contamination of the lungs.

We postulated that water condensate in endotracheal tubes (ETTs) transports bacteria in the ETTs into the lungs during mechanical ventilation. Thirty-two ETTs obtained from freshly extubated patients were studied under wet and dry conditions using a physiologic lung model. All bacteria expelled from the ETTs were collected on culture plates positioned beneath the ETT. The lung model was ventilated with saturated air at 37 degrees C over two time periods (60 min each), one in which condensation formation was prevented and the second in which condensation formed within the ETT. A mean of 457.6 colony-forming units (CFU)/h were expelled with condensation compared to a mean of 2.4 CFU/h without condensation. We concluded that bacteria were continuously transported from the ETT into the lungs during mechanical ventilation in water droplets. Prevention of water condensation abolishes this constant bacterial inoculation in a lung model.

Air Microbiology↗

Modification of cytochrome P450 1A2 enzymes by the mechanism-based inactivator 2-ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl.

2-Ethynylnaphthalene (2EN) had previously been demonstrated to be a mechanism-based inactivator of rat cytochrome P450 (P450) 1A2 [Hammons, G.J., Alworth, W.L., Hopkins, N.E., Guengerich, F. P., & Kadlubar, F. F. (1989) Chem. Res. Toxicol. 2, 367-374]. In this work 2EN was also demonstrated to be a useful inactivator of rabbit P450 1A2 (k(inactivation) 0.094 min-1, K(i) 11 microM) but it did not inactivate human P450 1A2, although the sequences of the three proteins are approximately 80% identical. Rat and rabbit P450 1A2 were modified by incubation with NADPH-P450 reductase, NADPH, and [3H]2EN to levels of 0.35 and 0.47 nmol of adduct (nmol of P450)-1, respectively. In each case only a single tryptic peptide was labeled; recovery of labeled peptides was low under the acidic HPLC conditions. The rabbit P450 1A2 peptide FQELMAAVGR (positions 175-184) and the rat P450 1A2 peptide L(S)QQYGDVLQIR (positions 67-78) were identified. 4-Azidobiphenyl (4-N3BP) was developed as a photoaffinity label for P-450 1A2 proteins because of its similarity to 4-aminobiphenyl, a known substrate for the enzymes. 4-N3BP was shown to be photolyzed with 350-nm light and radioactive label could be incorporated into rat P450 1A2. Labeling of the protein was found to be saturable with increasing concentrations of 4-N3BP and up to 0.59 nmol of label could be incorporated (nmol P450 1A2)-1. The substrate 4-aminobiphenyl and the competitive inhibitor 7,8-benzoflavone blocked photolabeling of P450 1A2 with 4-N3BP, and 4-N3BP inhibited N-hydroxylation of 4-aminobiphenyl by P450 1A2 in the usual enzyme assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

Structural and functional characterisation of recombinant human haemoglobin A expressed in Saccharomyces cerevisiae.

Recombinant human HbA, produced by co-expressing alpha-globin and beta-globin chains in the yeast Saccharomyces cerevisiae, has been characterised extensively both physically and functionally. Structural studies using N-terminal sequence analysis, peptide mapping, amino acid composition analysis and electrospray MS demonstrated that the recombinant protein was identical to standard HbA purified from erythrocytes. The functional properties of the recombinant protein were assessed using equilibrium and kinetic measurements of oxygen and carbon monoxide binding. The oxygen-binding studies demonstrated that the yeast-derived HbA behaved as a fully functional, cooperative tetramer (Hill coefficient, 2.9), exhibited a normal Bohr effect and response to phosphate, and displayed a rate of oxygen dissociation identical to that of the native human molecule. The recombinant protein also showed the same characteristics of carbon monoxide combination as the standard protein. These studies demonstrate that yeast provides an ideal system for the production of Hb for structural and functional analysis and a potentially useful source of HbA for formulation into a Hb-based oxygen carrier.

Amino Acids↗

Cardiac arrest in Ontario: circumstances, community response, role of prehospital defibrillation and predictors of survival.

OBJECTIVES: To describe the patient characteristics, circumstances and community response in cases of out-of-hospital cardiac arrest; to evaluate the effect on survival of the introduction of prehospital defibrillation; and to identify factors that predict survival. DESIGN: Population-based before-and-after clinical trial. SETTING: Five Ontario communities: London, Sudbury, the Greater Niagara region, Kingston and Ottawa. PATIENTS: A consecutive sample of 1510 primary cardiac arrest patients who were transported to hospital by ambulance over 2 years. INTERVENTION: The use of defibrillators by ambulance attendants. MAIN OUTCOME MEASURES: Patient characteristics (sex and age), circumstances of arrest (place, whether arrest was witnessed and cardiac rhythm), citizen response (whether cardiopulmonary resuscitation [CPR] was started by a bystander, time to access to emergency medical services and time to initiation of CPR), emergency medical services response (ambulance response time, time to initiation of CPR and time to rhythm analysis with defibrillator) and survival rates. MAIN RESULTS: A total of 92.1% of the patients were 50 years of age or older, and 68.3% were men. Overall, 79.6% of the arrests occurred in the home. The average ambulance response time for witnessed cases was 7.8 minutes. The overall survival rate was 2.5%. The survival rates before and after defibrillators were introduced were similar, and the general functional outcome of the survivors did not differ significantly between the two phases. Factors predicting survival included patient's age, ambulance response time and whether CPR was started before the ambulance arrived. CONCLUSIONS: The survival rate was lower than expected. The availability of prehospital defibrillation did not affect survival. To improve survival rates after cardiac arrest ambulance response times must be reduced and the frequency of bystander-initiated CPR increased. Once these changes are in place a beneficial effect from advanced manoeuvres such as prehospital defibrillation may be seen.

Adult↗

The Lancet's statistical review process: areas for improvement by authors.

The Lancet now incorporates statistical review of submitted papers which remain candidates for publication after conventional review. We summarise here criticisms noted by the statistical reviewers for 191 such papers received between November, 1990, and June, 1991. Only 54% of papers were deemed acceptable or acceptable after revision; the others were either recommended for rejection (14%) or for more substantial revision and re-review (32%). Descriptions of methods and of results were found inadequate in about half of the papers; about one-quarter of papers had inadequate abstracts and conclusions. Major errors of inference were made in 48 papers and went hand in hand with major criticisms of analysis or design in those papers. The natural focus of statistical review is whether conclusions drawn are justified by study design and statistical analysis. In this, there is room for improvement by authors.

Bias↗

Locoregional disease.

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Combined Modality Therapy↗

Polar metabolites of dihydrotachysterol3 in the rat. Comparison with in vitro metabolites of 1 alpha,25-dihydroxydihydrotachysterol3.

The metabolism of 25-hydroxydihydrotachysterol3 (25-OH-DHT3) to more polar metabolites was investigated in vivo in the rat and compared with the in vitro metabolism of 1 alpha,25-dihydroxy-DHT3 (1 alpha,25-(OH)2DHT3) in the osteosarcoma cell line UMR 106. Rats were given 2 mg of DHT3 in divided doses at 0 and 6 hr. Plasma was collected 24 hr after the initial dose, extracted, separated, and polar metabolites purified by HPLC. A number of polar metabolites were formed in vivo with mass spectrometric characteristics which suggested that they were derived from a previously isolated metabolite of 25-OH-DHT3, T3/H. Of these, four were isolated and identified as 24-oxo-T3/H, 24-hydroxy-T3/H, 26-hydroxy-T3/H and the 26,23-lactone of T3/H. In view of the identification of T3/H as a mixture of 1 alpha- and 1 beta-hydroxylated 25-OH-DHT3, osteosarcoma cells (UMR 106) were incubated with chemically synthesized 1 alpha,25-(OH)2DHT3 in an attempt to determine from which component of the T3/H mixture these metabolites were derived. Again, more polar metabolites were formed and five of these were isolated by lipid extraction, purified by HPLC and identified as 24-oxo-1 alpha,25-(OH)2DHT3, 1 alpha,23,25-(OH)3DHT3, 24-oxo-1 alpha,23,25-(OH)3DHT3, 1 alpha,24,25-(OH)3DHT3 and 1 alpha,25,26-(OH)3DHT3. Three of the in vitro metabolites were similar to those found in rat plasma but only two of these metabolites were available in sufficient amounts to allow comparison. The chromatographic characteristics, using HPLC and gas chromatography, of these two pairs of metabolites (24-oxo and 24-hydroxy) were examined and it was demonstrated that they were not the same. It is therefore suggested that the polar metabolites formed in vivo are in fact metabolites of the T3/Hb component (1 beta,25-(OH)2DHT3) rather than the T3/Ha component (1 alpha,25-(OH)2DHT3). Supporting evidence for this suggestion was obtained when a small quantity of 1 beta,25-(OH)2DHT3, obtained from chemically synthesized 1 beta-OH-DHT3 by incubation with Hep 3B cells, was further incubated in the osteosarcoma UMR 106 system. Preliminary studies indicated that the putative 24-oxo and 24-hydroxy metabolites formed from 1 beta,25-(OH)2DHT3 had chromatographic and mass spectral properties almost indistinguishable from those of corresponding metabolites of T3/H formed in vivo. All the metabolites formed in vivo and in vitro are components of two metabolic pathways described previously for 25-hydroxyvitamin D3 and also for 25-OH-DHT3.

Animals↗

Contrast variation studies of clathrin coated vesicles by small-angle neutron scattering.

Structural information on clathrin coated vesicles has been obtained by small angle neutron scattering using contrast variation. A characteristic peak in the neutron scattering profile, which is apparent in 75% D2O, as well as in H2O, disappears when contrast matching the protein component of the coated vesicles in 42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases when matching out the protein coat of the clathrin coated vesicles. From the match point for the clathrin coated vesicles it is demonstrated that the clathrin cages do contain internal membrane. The mass of 34 MD and composition of 75% protein and 25% lipid found from the analysis of the small-angle scattering data are both in good agreement with the values reported in the literature. Electron microscopy gives an average outer diameter of 880 A for the coated vesicles and an average diameter of 460 A for the vesicle itself.

Biophysical Phenomena↗