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Biomedical subjects

J Parker

Publications and source records attributed to J Parker.

At least 19 recordsLinked to original sources
PubMed1992

Misreading of the argI message in Escherichia coli.

It has previously been shown that either phenylalanine codon, UUU or UUC, could be misread as leucine during phenylalanine starvation, if the codons encoded residue 8 of the Escherichia coli argI gene product, ornithine transcarbamylase (OTC). However, no leucine misincorporation was detected when either of these same codons encoded residue 3. Here we report that leucine misincorporation can be directed by a UUU codon for residue 3 of OTC during phenylalanine starvation, if the argI gene has been mutated so that the codon preceding the UUU has been changed from the rarely used glycine codon GGG to the more commonly used GGC.

Amino Acid Sequence↗
PubMed1992

Sequence and characterization of the gcpE gene of Escherichia coli.

In Escherichia coli, the gene gcpE encodes a protein of unknown function and lies immediately upstream of the hisS gene for histidyl-tRNA synthetase. The nucleic acid sequence of gcpE predicts an open reading frame for a protein of 40,681 Da. The probable transcription terminator of gcpE overlaps the hisS promoter. Haploid cells containing a disrupted gcpE could not be obtained, suggesting that the gcpE gene is essential.

Amino Acid Sequence↗
PubMed1992

Poor prognosis associated with thrombocytosis in patients with cervical cancer.

The medical records of 113 patients treated with radiation therapy for invasive cervical cancer between 1975 and 1985 were retrospectively reviewed. Patients with thrombocytosis (platelet count greater than 400,000/microliters) were compared with those with normal platelet counts. Thrombocytosis was present at the initiation of therapy in 20 (17.7%) of the 113 patients. The 5-year cumulative survival rate for the 93 patients with normal platelet counts was 65%, whereas it was 25% for the 20 with thrombocytosis (P less than 0.0001, log-rank test). Using Cox's proportional hazards model, thrombocytosis continued to correlate strongly with poor survival even when adjusted for histologic type, patient age, and disease stage (P less than 0.001). Thrombocytosis is an independent indicator of poor prognosis in patients with cervical cancer.

Female↗
PubMed1992

The bioluminescent detection of platelet released ATP: collagen-induced release and potential errors.

The bioluminescent detection of ATP released from activated platelets is an important diagnostic and experimental assay. Potential errors in the interpretation of the data may be introduced due to the lability of luciferin-luciferase and the amount of platelet agonist employed. Loss of luciferin-luciferase activity is temperature dependent with a 50% decrease in activity in 1-4 min at 37 degrees C. Plasma components do not appear to contribute to the inactivation of the detection system. Due to the significant loss of enzyme activity at variable times, the method of standardizing ATP concentrations is crucial for the accurate determination of ATP released from activated platelets. A nearly 5-fold error is introduced into the routinely employed assay procedure where the standard ATP concentration is determined 5 min after the addition of agonist. This report demonstrates that the standard ATP concentration must be determined with a separate platelet sample at the same time as the ATP was released from the agonist-induced experimental platelet sample. A second significant error in the assay system may be introduced by the agonist concentration employed even when the final level of aggregation is the same. When collagen is employed as the agonist the amount of ATP released appears to depend, in part, on the initial intensity of the aggregation response and not on collagen type (Type I versus IV). The corrective procedures described here for the detection of ATP are not likely to change the qualitative results of most studies but would significantly alter the quantitative results.

Adenosine Triphosphate↗
PubMed1992

Formation of a prostaglandin A2-glutathione conjugate in L1210 mouse leukemia cells.

Prostaglandins containing a cyclopentenone moiety are potent antiviral and antigrowth compounds. Some evidence indicates that these prostaglandins are conjugated to glutathione by cells. However, the metabolism of one group, the prostaglandins of the A type, is unclear due to conflicting reports. We studied the uptake and metabolism of prostaglandin A2 (PGA2) in mouse L1210 leukemia and L929 fibroblast cell lines in which this prostaglandin has antiviral and antigrowth effects. Both cell types took up the PGA2 and then metabolized it to a more polar compound. Inside L1210 cells, PGA2 was initially conjugated to glutathione and then reduced at the 9-keto position to form 9-OH-PGA2-GSH. The 9-OH-PGA2-GSH was then secreted from the cells and apparently degraded to form the CysGly and Cys derivatives. Intracellular glutathione was decreased markedly by the addition of the PGA2 in L1210 and L929 cells. This result confirms that conjugation of PGA2 to glutathione occurs in both cell types. Formation of the 9-OH-PGA2-GSH and other glutathione-related conjugates was prevented when glutathione was depleted by growth in buthionine sulfoximine. The glutathione-depleted cells were insensitive to the cytotoxicity of the PGA2, suggesting that one of the glutathione-related conjugates may be involved in the cytotoxicity of PGA2. These results end the controversy over the metabolism of PGA2 and suggest mechanisms for its antiviral and antigrowth actions.

Animals↗
PubMed1992

Geometrically accurate activation mapping of the atrioventricular node region during surgery.

A novel method has been developed to map activation in the triangle of Koch during surgery for cardiac arrhythmias and relate the map to anatomic landmarks. It uses a hand-held electrode mounted in a freely moving linkage that has three degrees of mechanical freedom. The movements of the linkage are sensed by a computer that continuously calculates the coordinates of the electrode. The surgeon clamps the device over the triangle of Koch after the right atrium has been opened and uses the electrode to trace the anatomic landmarks of the region that are displayed on the computer screen. The position of the electrode is displayed continuously relative to these landmarks and electrograms are recorded at known positions to generate a map. The activation sequences during sinus rhythm, atrioventricular node reentrant tachycardia, "common" and "uncommon" atrial flutter, long RP' tachycardia and retrograde conduction through paranodal pathways are presented. It is concluded that 1) the high spatial resolution reveals physiologically important areas in the maps that are 8 mm long and 3 mm wide and that these areas can be related to specific anatomic landmarks; 2) there are complex electrograms in the region that may reflect the activation of different myocardial layers; and 3) there are marked changes in conduction velocity and direction within the region.

Atrial Flutter↗
PubMed1992

Auditing audits.

Explore the source record for details and available documents.

England↗
PubMed1992

The effect of dry and humid hot air inhalation on expired relative humidity during exercise.

It has been previously demonstrated that under certain environmental conditions, expired air is not fully water saturated because of the low relative humidity of the first part of the expirate. This finding is of interest to those involved in respirator research, particularly those who design and test robotic metabolic simulators. These simulators must accurately mimic the physiological responses of human airways to breathing air of various temperatures and relative humidities (RHs). Because these responses are not fully quantified, this study examined the mean relative humidity of expired air during four inspired air conditions: cool dry (26 degrees C, 60% RH), cool humid (26 degrees C, 95% RH), hot dry (45 degrees C, 11% RH), and hot humid (45 degrees C, 95% RH). These conditions were administered during three exercise intensities: rest, low (35% VO2max), and moderate (70% VO2max). As compared to the cool dry (CD) condition, frequency of breathing (f) was 9.3% lower and tidal volume (VT) was 9.4% greater across all exercise intensities for the hot humid (HH) condition (p less than 0.05). Mean expired relative humidity (ERH) was substantially lower for the hot dry (HD) condition as compared to the other three conditions during each sampling period. These findings support the conclusion that the mean ERH of expired air depends upon several respiratory and environmental factors in addition to inspired air temperature.

Adolescent↗
PubMed1992

Relationship of changes in helplessness and depression to disease activity in rheumatoid arthritis.

We investigated the relationship between changes in helplessness and depression to disease activity in rheumatoid arthritis (RA). Sixty-three men with RA were examined at baseline, 3 months, and 6 months. Joint counts, immunophenotypic analyses of peripheral blood lymphocytes, and measures of psychological status were obtained at each examination. Zero-order correlations between psychological change and disease activity change from baseline to 6 months were not significant, but hierarchical multiple regression analyses revealed that changes in affective state were significantly related to joint counts at 6 months. Additionally, changes in absolute numbers of HLA-DR+ (human leukocyte antigen DR type) cells were significantly related to joint counts at 6 months. When absolute numbers of HLA-DR+ cells were entered prior to affective state in a hierarchical multiple regression, affective state was only marginally statistically significant. The study shows that longitudinal relationships between affective changes and disease activity are moderated by intervening variables such as immunologic activation.

Aged↗
PubMed1992

Fractures of the femur treated by intramedullary nailing using the fluted rod. A report of 193 consecutive cases.

One hundred ninety-three of 196 acute nonpathologic femoral shaft fractures were treated consecutively with intramedullary nailing using the fluted rod. Closed intramedullary nailing was used in 126 fractures, and an open technique was used in 67. This series includes 58 open fractures and 104 comminuted fractures. All fractures treated with the fluted rod united. Complications included three superficial infections (1.5%). Malrotation greater than 20 degrees was noted in six patients (3.1%). Significant shortening (5 cm), which required treatment, occurred in one patient. After initial resuscitation and evaluation, routine treatment included preoperative traction and a first-generation cephalosporin followed by accurate reduction and nailing of the fracture. The results of this series suggest that the fluted rod may be ideal for the treatment of most femoral shaft fractures.

Adolescent↗
PubMed1991

Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival.

In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained.

Adult↗
PubMed1991

Codon usage, transfer RNA availability and mistranslation in amino acid starved bacteria.

The fidelity of codon reading was examined in amino acid starved Escherichia coli. In one case the level of misincorporation of methionine was measured at an isoleucine residue encoded by either the commonly used AUU codon or the rarely used AUA codon. In this situation we found the frequency of methionine misincorporation to be very low and to be unaffected by the identity of the isoleucine codon. In other experiments histidine misincorporation for glutamine was measured in glutamine starved cells with normal levels of histidine-specific tRNA and cells overproducing this tRNA. Cells overproducing the tRNA had higher levels of misincorporation.

Amino Acid Sequence↗
PubMed1991

Comparison of immunogenicity of two yeast-derived recombinant hepatitis B vaccines.

A comparison was conducted of the immunogenicity of two yeast recombinant vaccines with different doses [10 micrograms Recombivax-HB (Merck Sharpe & Dohme Ltd) vs. 20 micrograms Engerix-B (Smith Kline Biologicals)]. This was conducted as a randomized, blinded study in healthy preclinical medical students, negative for hepatitis B markers. The geometric mean titres (GMT) showed a wide individual variability for both vaccines, and approximately a two- to threefold greater GMT of anti-HBs in recipients of the 20 micrograms vaccine. However, the 95% confidence interval showed an overlap of the means of the GMT for both vaccine groups, and in this study there was no significant difference in immunogenicity of these two vaccines. At 6-7 months after completion of immunization, antibody levels fell to one-third of the levels of one month post-immunization. A case report of an allergic urticarial reaction to one of the recombinant vaccines is presented.

Adult↗
PubMed1991

Modeling benzene pharmacokinetics across three sets of animal data: parametric sensitivity and risk implications.

Typically, the uncertainty affecting the parameters of physiologically based pharmacokinetic (PBPK) models is ignored because it is not currently practical to adjust their values using classical parameter estimation techniques. This issue of parametric variability in a physiological model of benzene pharmacokinetics is addressed in this paper. Monte Carlo simulations were used to study the effects on the model output arising from variability in its parameters. The output was classified into two categories, depending on whether the output of the model on a particular run was judged to be generally consistent with published experimental data. Statistical techniques were used to examine sensitivity and interaction in the parameter space. The model was evaluated against the data from three different experiments in order to test for the structural adequacy of the model and the consistency of the experimental results. The regions of the parameter space associated with various inhalation and gavage experiments are distinct, and the model as presently structured cannot adequately represent the outcomes of all experiments. Our results suggest that further effort is required to discern between the structural adequacy of the model and the consistency of the experimental results. The impact of our results on the risk assessment process for benzene is also examined.

Animals↗