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Biomedical subjects

G R Jones

Publications and source records attributed to G R Jones.

At least 55 records · Page 3Linked to original sources
PubMed1996

Urokinase in the treatment of bacteremia and candidemia in patients with right atrial catheters.

BACKGROUND: Urokinase plasminogen activator was used in combination with antibiotic therapy given through the catheter to improve the treatment of right atrial catheter infections. METHODS: One hundred fifty-four episodes of bacteremia and candidemia occurring in 97 children with malignant or hematologic conditions were treated. After 24 hours of antibiotic therapy, 1 ml urokinase (5000 units/ml) was instilled, dwelling 1 hour, and then removed; this was repeated within 24 hours. Antibiotic therapy was continued for then removed; this was repeated within 24 hours. Antibiotic therapy was continued for 10 to 35 days. Administration of urokinase was repeated once if infection recurred within 8 weeks of initial treatment. RESULTS: There were no adverse affects from administration of urokinase. Bacteremia clearance failed after initial administration of urokinase in 12 episodes; this failure was mostly associated with the presence of gram-positive organisms. Blood culture results remained positive in three cases after repeat therapy. Bacteremia recurred in 15 of 125 episodes; in three cases bacteremia did not clear after repeat administration of urokinase or recurred again. Recurrence was lowest for gram-negative organisms and Candida sp. Less than 5% of catheters were removed as a result of treatment failure. CONCLUSIONS: Administration of urokinase combined with antibiotic therapy is safe and may be effective in treating bacteremia and candidemia in patients with right atrial catheters. Use of urokinase may improve treatment of organisms that are otherwise difficult to control and may prevent recurrence of infection.

Adolescent↗
PubMed1996

Successful cancer therapy with promethazine: the rationale.

Evidence supporting the claim that specific phenothiazines, notably chlorpromazine and promethazine, may be used as sole agents for the treatment of cancer in man, has been reviewed. Selective destruction of cancerous tissue can be achieved by modulating energy metabolism in malignant cells. In the light of available information, the drug of choice is promethazine, the effects of which on the central nervous system are relatively weak. The maintenance of continuous pharmacological pressure against malignant growths forms an essential feature of the therapy. Protection against blood dyscrasias may be secured through the provision of adequate amounts of trace elements necessary for the function of enzyme systems which detoxicate active oxygen species. Tumour-cell death may be facilitated by nutritional supplements of specific polyunsaturated fatty acids. Interference from adventitious medications and drug resistance are discussed; appropriate therapy is outlined.

Antineoplastic Agents↗
PubMed1996

The experience of work and turnover intentions: interactive effects of value attainment, job satisfaction, and positive mood.

The researchers proposed that the phenomenological experience of work is multifaceted and that simultaneously considering the combined effects of the different aspects of the work experience holds considerable promise for increasing understanding of turnover intentions and other organizationally relevant outcomes. Research in subjective well-being and other areas suggests that there are 3 important aspects of the experience of work: attainment of values, attitudes, and moods. It was hypothesized and found that the relationship between job satisfaction and turnover intentions is jointly moderated by value attainment and positive mood. The nature of this triple interaction was such that the job satisfaction-turnover intention relationship was strongest when workers' jobs did not help them to attain terminal values and positive moods were experienced, and the relationship was weakest when jobs helped workers to attain terminal values and positive moods were experienced.

Adult↗
PubMed1996

High-resolution confocal microscopy using synchrotron radiation.

A confocal scanning light microscope coupled to the Daresbury Synchrotron Radiation Source is described. The broad spectrum of synchrotron radiation and the application of achromatic quartz/CaF2 optics allows for confocal imaging over the wavelength range 200-700 nm. This includes UV light, which is particularly suitable for high-resolution imaging. The results of test measurements using 290-nm light indicate that a lateral resolution better than 100 nm is obtained. An additional advantage of the white synchrotron radiation is that the excitation wavelength can be chosen to match the absorption band of any fluorescent dye. The availability of UV light for confocal microscopy enables studies of naturally occurring fluorophores. The potential applications of the microscope are illustrated by the real-time imaging of hormone traffic using the naturally occurring oestrogen coumestrol. (The IUPAC name for coumestrol is 3,9-dihydroxy-6H-benzofurol[3,2-c][1]benzo-pyran-6-one (Chem. Abstr. Reg. No. 479-13-0). The trivial name will be used throughout this paper.

Animals↗
PubMed1996

The systemic inflammatory response syndrome as a predictor of bacteraemia and outcome from sepsis.

Criteria defining the systemic inflammatory response syndrome (SIRS) were used to assess prospectively 270 clinical episodes in which blood cultures were taken from patients in general medicine. SIRS, severe sepsis and septic shock occurred in 149 (55%), 13 (5%) and 9 (3%) episodes, respectively. However, evidence of organ hypoperfusion indicating severe sepsis was recorded as sought in only 26% of episodes of SIRS. Crude mortality at 28 days increased sequentially as more SIRS criteria were met, rising from 12% in non-SIRS blood culture episodes, to 36% when all four criteria were met. Mortality from severe sepsis and septic shock was 38% and 56%, respectively. In 61/64 (95%) episodes of clinically important bacteraemia, patients fulfilled SIRS criteria when the blood culture was taken. However, the positive predictive value of SIRS for predicting bacteraemia was only 7%. Patients who did not fulfil SIRS criteria when blood cultures were taken were at low risk of bacteraemia and comprised 45% (121/270) of the study population. Three patients in this low-risk group had bacteraemia. Mortality in bacteraemic patients with severe sepsis or septic shock who were initially treated with ineffective antibiotics for up to 48 h was 80%, compared to 42% in those always treated appropriately.

Adolescent↗
PubMed1995

Evidence for sodium dodecyl sulfate/protein complexes adopting a necklace structure.

Structural analysis by cryo-electron microscopy and small-angle X-ray scattering of ten sodium dodecyl sulfate/protein complexes in 25 mM Tris/HCl, 0.192 M glycine, pH 8.3, showed necklace-like structures of spherical micelles dispersed along the unfolded peptide chain. The micelles of most SDS/protein complexes had a constant diameter (approximately 6.2 nm), slightly larger than pure SDS micelles (approximately 5.7 nm), all micelles possessing a degree of surface roughness. The micelle-associated polypeptide is mostly situated at the interface of the sulfate head groups and hydrocarbon core, intruding into the core rather than outward from the surface. Proteins with a molecular mass less than about 20 kDa formed complexes with a single SDS micelle. Multi-micellar SDS/protein complexes had centre-to-centre intermicellar distances in the range 7.0-12.0 nm. Our findings on the constancy of micellar size, number of micelles/complex, and the relationship between the degree of occupancy of micelles and a polypeptide's molecular mass, have enabled us to speculate on the correlation between the electrophoretic mobility of a polypeptide in SDS/PAGE and its molecular mass. The anomalous electrophoretic behaviour observed for the sodium dodecyl sulfate/histone H5 complex is accounted for by the large micelle of its complex.

Freezing↗
PubMed1995

Properties of the soluble polypeptide of the proton-translocating transhydrogenase from Rhodospirillum rubrum obtained by expression in Escherichia coli.

Transhydrogenase, which catalyses the reduction of NADP+ by NADH coupled to proton translocation across a membrane, may be unique in the photosynthetic bacterium Rhodospirillum rubrum. Unlike the homologous enzyme from animal mitochondria and other bacterial sources, it has a water-soluble polypeptide, which exists as a dimer (Ths), that can be reversibly dissociated from the membrane component [Williams, R., Cotton, N. P. J., Thomas, C. M. & Jackson, J. B. (1994) Microbiology, 140, 1595-1604]. We have expressed the gene for Ths in cells of Escherichia coli under control of the tac promoter and a strong ribosome binding site. The protein, purified by column chromatography, fully reconstituted transhydrogenation activity to everted membrane vesicles of Rhs. rubrum that had been washed to remove Ths. The purified expressed protein was prepared in quantities over 100-fold greater than were obtained from wild-type Rhs. rubrum. The fluorescence spectrum of purified expressed Ths had an intense and unusually short wavelength emission maximum at 310 nm with shoulders at 298 and 322 nm. Time-resolved measurements indicated that the fluorescence decay was almost monoexponential with a lifetime of 5.2 ns. On denaturation with 4 M guanidine hydrochloride, the emission band shifted to 352 nm and decreased in intensity. In the native protein, the fluorophore was relatively inaccessible to quenching solutes, such as iodide ions and acrylamide. It is concluded that the fluorescence emission arises mainly from the single tryptophan residue of Ths (Trp72), which is locked into a rigid conformation and is located in highly non-polar environment. The 310-nm fluorescence of Ths was quenched by NADH, maximally to 46%. The apparent binding constant was 18 microM. The fluorescence of Ths-bound NADH was enhanced relative to the nucleotide in free solution and its emission maximum was shifted to a shorter wavelength (440 nm). These data support previous indications that the NADH binding site is located in domain I of proton-translocating transhydrogenase. Excitation of Ths at 280 nm did not lead to sensitized emission at 440 nm from bound NADH. This indicates that the quenching of fluorescence of Ths by NADH does not result from resonance energy transfer from Trp72 to the bound nucleotide. NAD+, NADP+ and NADPH had little effect on the protein fluorescence. The kinetics of quenching of Ths fluorescence by NADH were examined after mixing in a stopped-flow device. The 'on' rate constant for nucleotide binding was approximately 8 x 10(6) M-1 s-1 and the 'off' constant approximately 150 s-1.

Amino Acid Sequence↗
PubMed1995

Characterization of IHNV isolates associated with neurotropism.

Rainbow trout with a 'neurotropic' form of infectious hematopoietic necrosis (IHN) exhibited behavioral abnormalities and had high virus concentrations localized in brain tissue. Fish with 'hematopoietic' IHN exhibited typical disease signs with the highest concentrations of virus detected in kidney-spleen tissue. Infectious hematopoietic necrosis virus (IHNV) isolates obtained from brain or kidney-spleen tissue were tested for serological relatedness and virulence and pathogenicity differences in 2 sizes of rainbow trout. No major differences were detected by indirect fluorescence tests. Serum neutralization profiles showed 2 predominant patterns that differed dependent upon tissue of origin. However, virulence and pathogenicity differences were not evident.

Animals↗
PubMed1995

Aquareovirus interference mediated resistance to infectious hematopoietic necrosis virus.

This study investigated the stimulation of specific host defenses to IHNV that are created by prior exposure to an avirulent reovirus (chum salmon reovirus; CSV). Preexposure of rainbow trout to CSV for 1 h resulted in a relative percent survival that ranged from 68 to 100% when fish were challenged with IHNV over an 8 week period. The levels of serum neutralizing antibodies detected 28 d after the IHNV challenge were significantly lower among fish receiving prior exposures to CSV than among non-CSV-treated fish. The differences in the humoral response to IHNV in the CSV-treated fish suggested that other immune defense mechanisms may be involved.

Animals↗
PubMed1994

Risk factors for recurrent fever after the discontinuation of empiric antibiotic therapy for fever and neutropenia in pediatric patients with a malignancy or hematologic condition.

We studied episodes of fever and neutropenia in children and adolescents without documented infections to determine the risk of recurrent fever after early discontinuation of empiric antibiotic therapy; 213 episodes occurred in 106 patients. All patients received empiric antibiotic therapy after cultures were obtained. Antibiotic therapy was discontinued if no infection was found, culture results were negative for 48 hours, and the patient was afebrile for 24 hours. In 83 episodes without documented infection, antibiotic therapy was stopped with absolute neutrophil counts < 0.5 x 10(9)/L (< 500/mm3); 50 episodes occurred in patients with solid tumors, leukemia in remission, and other hematologic conditions (group 1), and 33 in patients with active leukemia (group 2). Fever recurred before neutropenia resolved in 6% of group 1 and 45% of group 2 episodes; five patients in group 2 had documented infection. Recurrent fever risk correlated with absolute neutrophil count and monocyte count at the time antibiotic therapy was stopped, in both groups, as did increasing absolute neutrophil count and increasing leukocyte count in group 2. We conclude that discontinuing antibiotic therapy is safe in febrile episodes without documented infections before neutropenia resolves in patients with high potential for bone marrow recovery. The risk of recurrent fever and infection is significant for patients with neutropenia and poor marrow recovery potential.

Adolescent↗
PubMed1993

A near perfect temperature adaptation of bilayer order in vertebrate brain membranes.

The bilayer order of a brain synaptic membrane fraction from a number of fish, mammalian and avian species have been compared in relation to their respective body temperatures using steady-state and time-resolved fluorescence anisotropy techniques. Fluorescence anisotropy for both 1,6-diphenyl-1,3,5-hexatriene and trans-parinaric acid increased in the order: antarctic Notothenia, trout, perch, cichlid, rat and starling, this also being the order of increasing body temperature. This suggests that cold-adapted fish species possess more disordered brain membranes than warm-adapted fish species, and mammals and birds membranes were more ordered than fish membranes. Comparison of temperature profiles for both fluorescence probes showed that fish species display similar anisotropies, and by inference bilayer order, to mammals and birds when measured at their respective body temperatures. Time-resolved analysis showed that the interspecific differences in (P2) order parameter was consistently related to body temperature whilst the rotational diffusion coefficient was not. These results suggest that brain membrane order is highly conserved within the vertebrates despite large differences in thermal habits and phylogenetic position. Polar fish species have by far the lowest bilayer order indicating that invasion of extreme cold habitats involved an adaptive decrease in bilayer order and conversely adoption of a high body temperature by mammals involved an adaptive increase in bilayer order. The conservation of membrane static order for these species at their respective body temperatures indicates a regulatory control of this aspect of membrane hydrocarbon structure and the functional importance of this structure.

Adaptation, Physiological↗
PubMed1993

Chronic Nocardia asteroides endophthalmitis after extracapsular cataract extraction.

A 65-year-old man underwent an uncomplicated extracapsular cataract extraction with placement of a posterior chamber intraocular lens. The patient developed delayed-onset chronic endophthalmitis caused by Nocardia asteroides. This was confirmed on multiple intraocular cultures, as well as histopathologic examination of the lens capsular bag. The patient was treated with periocular, intravitreal, and systemic antibiotic treatment, combined with intraocular lens removal, total capsulectomy, and three vitrectomies in an attempt to eradicate the organism and calm the eye. The patient went on to develop widespread endophthalmitis that required enucleation of the infected globe. To our knowledge, this is the first case of delayed-onset chronic endophthalmitis caused by N asteroides after extracapsular cataract extraction with a posterior chamber intraocular lens.

Aged↗
PubMed1993

Prospective analysis of urokinase in the treatment of catheter sepsis in pediatric hematology-oncology patients.

Use of right atrial catheters (RACs) in children with cancer improves the comfort and efficacy of therapy. However, catheter-related infections are responsible for significant morbidity leading to the removal of approximately 20% of implanted RACs. Sepsis has been linked to thrombus and fibrin sheath formation within the RAC. Gram-negative and fungal infections appear to be particularly resistant to antibiotic therapy alone and most of these infections have required catheter removal. Urokinase has been effectively used for reopening thrombus occluded RACs. Theoretically, thrombolytic agents could improve the treatment of catheter-related infections by removing luminal sites of bacterial/fungal colonization. We prospectively monitored the use of urokinase and antibiotics for catheter-related sepsis in our pediatric hematology/oncology population from 1985 to 1991. Sepsis episodes were treated with 2 doses of urokinase and antibiotics (10 to 42 days) infused through the RAC. One to 2 mL of urokinase (5,000 U/mL) was instilled in the RAC for 1 hour, then removed and repeated 24 hours later. During the study, 224 RACs were placed in 177 children. RACs were in place for a total of 71,134 days (median, 274 days). There were 67 blood culture-positive sepsis episodes occurring in 50 RACs. Fifty-nine sepsis episodes were treated with urokinase and antibiotics and all responded by clearance of organisms from the blood. Three patients (5.1% of urokinase treated) had recurrent sepsis with the same organism within 2 months, were considered treatment failures and had RACs removed. Only 1 of 16 episodes of multiple organism/Candida sepsis led to RAC removal due to inability to cure the infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Bone marrow histiocytic proliferation in association with colony-stimulating factor therapy.

A 6-year-old white male had a myelodysplastic syndrome (refractory anemia with excess blasts in transformation) and was treated with high dose chemotherapy. A combined esterase stain of the marrow blasts showed granulocytic differentiation. Subsequently, persistent pancytopenia with a severely hypocellular bone marrow developed, which was treated with a combination of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Sixteen days after the initiation of therapy, histologic examination of the bone marrow revealed a marked proliferation of histiocytes. To the best of the authors' knowledge, this is the first report of histiocytic proliferation in the bone marrow after colony-stimulating factor therapy.

Bone Marrow↗
PubMed1993

Quantification of lipoprotein(a) particles containing various apolipoprotein(a) isoforms by a monoclonal anti-apo(a) capture antibody and a polyclonal anti-apolipoprotein B detection antibody sandwich enzyme immunoassay.

A quantitative sandwich ELISA for lipoprotein(a) [Lp(a)], utilizing a monoclonal capture antibody that recognizes human and rhesus monkey apolipoprotein(a) [apo(a)] isoforms in combination with a polyclonal anti-apolipoprotein B-peroxidase conjugate was developed. This assay generates a linear calibration curve from 31.2 to 1000 mg/L, is highly reproducible (intra- and interassay CV of < 5% and < or = 12%, respectively), and shows no interference from plasminogen (1 g/L), low-density lipoprotein (6.00 g/L), triglycerides (27.00 g/L from chylomicrons and 10.00 g/L from very-low-density lipoprotein), hemoglobin (5 g/L), or bilirubin (30 mg/L). This assay format quantifies the concentration of Lp(a) on an equal molar basis regardless of apo(a) isoform. In contrast, a commercially available ELISA [Macra Lp(a)] method with a monoclonal anti-apo(a) capture antibody and a polyclonal anti-apo(a) conjugate was found to underestimate the Lp(a) concentrations of individuals with lower-M(r) apo(a) isoforms--whether quantifying the Lp(a) in plasma or the purified lipoprotein. This demonstrates the importance of assay format selection in quantifying Lp(a).

Animals↗