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Biomedical subjects

G Archer

Publications and source records attributed to G Archer.

At least 19 recordsLinked to original sources
PubMed2001

A comparative view of the new journal: Assessment.

The reference sections from all articles in the 1997 volumes of Assessment, Journal of Personality Assessment, and Psychological Assessment were entered into a database and analyzed. An article published in Assessment averaged almost 31 references. An article published in Journal of Personality Assessment contained an average of 33 references. Psychological Assessment averaged 38 references per article. The median age of the references in the three journals was 8 years with an interquartile range of 4 to 14 years. The Journal of Personality Assessment had the largest number of citations in this database of 5,316 references. Each of these received a relatively large number of their citations from articles published in the same journal (self-citations). Randomly selected articles from the 1997 volume of Assessment received fewer citations in the Social Science Citation Index than a similar set of articles from the other two journals. However, the data on Assessment, when compared with data available on other new scientific publications, suggests that Assessment is doing as well as other fledgling journals.

Bibliometrics↗
PubMed2000

Increased binding affinity enhances targeting of glioma xenografts by EGFRvIII-specific scFv.

Combinatorial variation of CDR3 of V(H) and V(L), followed by phage display, was used to select affinity mutants of the parental anti-epidermal growth factor receptor-vIII (EGFRvIII) scFv MR1. One mutant, MR1-1(scFv), had increased specific binding affinity for EGFRvIII. It was produced and radiolabeled, and its biodistribution was evaluated in human glioma-bearing athymic mice. MR1-1 targeted the same EGFRvIII epitope as MR1 with an approximately 15-fold higher affinity (K(d) = 1.5 x 10(-9) M) measured by surface resonance analysis. Labeling with (131)I or (125)I was performed, and the immunoreactive fraction of the labeled MR1-1(scFv) was 50% to 55%. After incubation at 37 degrees C for 4 days, the binding affinity was maintained at 60% of initial levels. The specificity of MR1-1 for EGFRvIII was demonstrated in vitro by flow cytometry and incubation of FITC-labeled scFv with the EGFRvIII-expressing U87MG. DeltaEGFR cell line or with the EGFRvIII-negative U87MG cell line in the presence or absence of competing unlabeled MR1-1(scFv). We also investigated the internalization and processing of MR1-1 compared with MR1; MR1-1 exhibited levels of both cell surface retention and internalization up to 5 times higher than those by MR1. In biodistribution studies performed in athymic mice bearing s.c. U87MG. DeltaEGFR tumor xenografts, animals received paired-label intratumoral infusions of (131)I-labeled MR1-1(scFv) and (125)I-labeled MR1(scFv). Our results showed an up to 244% +/- 77% increase in tumor uptake for MR1-1 compared with that for MR1. The improved tumor retention of MR1-1(scFv) combined with its rapid clearance from normal tissues also resulted in sustained higher tumor:normal organ ratios. These results suggest that the improved affinity of MR1-1 can significantly impact in vivo glioma-specific targeting and immunotherapy.

Amino Acid Sequence↗
PubMed1999

125I-labeled anti-epidermal growth factor receptor-vIII single-chain Fv exhibits specific and high-level targeting of glioma xenografts.

A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a deletion in its extracellular domain that results in the formation of a new, tumor-specific antigen found in glioblastomas, breast carcinomas, and other tumors. The scFv molecule, designed as V(H)-(Gly4-Ser)3-V(L), was expressed in Escherichia coli in inclusion body form; recovered scFv fragments were properly refolded in redox-shuffling buffer. Size-exclusion chromatography of purified scFv demonstrated a protein monomer of Mr 26,000. Labeling was performed using N-succinimidyl 5-[125I]iodo-3-pyridinecarboxylate (SIPC) or Iodogen to specific activities of 0.5-2.0 mCi/mg, with yields of 35-50% and 45-70%, respectively. The immunoreactive fraction (IRF) of the labeled MR1(scFv) was 65-80% when SIPC was used and 50-55% when Iodogen was used. The affinity (K(A)) of MRI(scFv) for EGFRvIII was 4.3 x 10(7) +/- 0.1 x 10(7) M(-1) by BIAcore analysis, and it was 1.0 x 10(8) +/- 0.1 x 10(8) M(-1) and by Scatchard analysis versus EGFRvIII-expressing cells. After incubation at 37 degrees C for 24 h, the binding affinity was maintained, and the IRF was maintained at 60-70%. The specificity of MR1(scFv) for EGFRvIII was demonstrated in vitro by incubation of radiolabeled MR1(scFv) with the EGFRvIII-expressing U87MG.deltaEGFR cell line in the presence or absence of competing unlabeled MR1(scFv) or anti-EGFRvIII MAbs L8A4 and H10. In biodistribution studies using athymic mice bearing s.c. U87MG.deltaEGFR tumor xenografts, animals received intratumoral or i.v. infusions of paired-label [125I]SIPC-MR1(scFv) and [131I]SIPC-anti-Tac(scFv) as a control. When given by the intratumoral route, MR1(scFv) retained high tumor uptakes of 85% injected dose per gram of tissue at 1 h and 16% injected dose per gram of tissue at 24 h following administration. Specific: control scFv tumor uptake ratios of more than 20:1 at 24 h demonstrated specific localization of MR1(scFv). The excellent tumor retention of MR1(scFv), combined with its rapid clearance from normal tissues, resulted in high tumor:normal organ ratios.

Amino Acid Sequence↗
PubMed1994

Comparison of traditional and molecular methods of typing isolates of Staphylococcus aureus.

Fifty-nine Staphylococcus aureus isolates and 1 isolate of Staphylococcus intermedius were typed by investigators at eight institutions by using either antibiograms, bacteriophage typing, biotyping, immunoblotting, insertion sequence typing with IS257/431, multilocus enzyme electrophoresis, restriction analysis of plasmid DNA, pulsed-field or field inversion gel electrophoresis, restriction analysis of PCR-amplified coagulase gene sequences, restriction fragment length polymorphism typing by using four staphylococcal genes as probes, or ribotyping. Isolates from four well-characterized outbreaks (n = 29) and a collection of organisms from two nursing homes were mixed with epidemiologically unrelated stock strains from the Centers for Disease Control and Prevention. Several isolates were included multiple times either within or between the sets of isolates to analyze the reproducibilities of the typing systems. Overall, the DNA-based techniques and immunoblotting were most effective in grouping outbreak-related strains, recognizing 27 to 29 of the 29 outbreak-related strains; however, they also tended to include 3 to 8 epidemiologically unrelated isolates in the same strain type. Restriction fragment length polymorphism methods with mec gene-associated loci were less useful than other techniques for typing oxacillin-susceptible isolates. Phage typing, plasmid DNA restriction analysis, and antibiogram analysis, the techniques most readily available to clinical laboratories, identified 23 to 26 of 29 outbreak-related isolates and assigned 0 to 6 unrelated isolates to outbreak strain types. No single technique was clearly superior to the others; however, biotyping, because it produced so many subtypes, did not effectively group outbreak-related strains of S. aureus.

Bacterial Typing Techniques↗
PubMed1991

Human immunodeficiency virus antibodies in sera of Australian blood donors: 1985-1990.

OBJECTIVE: To describe the results of human immunodeficiency virus type 1 (HIV-1) antibody testing of blood donations in Australia. DESIGN: Blood transfusion services tabulated the number of HIV-1 antibody tests carried out on blood donations and the number of donations found to be positive, from 1985 to 1990. SETTING: All blood transfusion services in Australia. PARTICIPANTS: All donors of blood in Australia from 1 May 1985 to 31 December 1990. OUTCOME MEASURES: The proportion of blood donations found to have HIV-1 antibody, according to State or Territory, year of donation and, when available, age, sex and donation status (repeat or first-time) of the donor. RESULTS: To the end of December 1990, 5,367,970 donations had been tested for HIV-1 antibody, and 46 were found to have the antibody, giving an overall prevalence rate of 0.86 per 100,000 donations. The highest rate was recorded in New South Wales, followed by Western Australia, and four of eight Australian States and Territories reported no donors with HIV-1 antibody. There has been no clear trend with time, but the rate is about 20% higher for 1989-1990 than for 1985-1986. Of donors found to have HIV-1 antibody, 67% were male and 33% female, and 41% reported no known or potential exposure to HIV-1 other than heterosexual contact. Among blood donors in two major Australian cities, the overall prevalence of HIV antibody was higher in those who were male, younger, and first-time donors. There has been a recent increase in the number of blood donors with HIV-1 antibody who were women reporting heterosexual contact as their only potential exposure. CONCLUSION: The rate of HIV-1 antibody in Australian blood donations remains very low and shows no clear temporal trend, but specific donor characteristics define higher rates of antibody prevalence.

Adult↗
PubMed1989

Low-level methicillin resistance in strains of Staphylococcus aureus.

Two strains of Staphylococcus aureus expressing borderline or low-level methicillin resistance by one or more in vitro test methods were examined for resistance in vivo and for biochemical and genetic markers of methicillin resistance. In vivo, nafcillin was equally effective against experimental aortic valve endocarditis in rabbits, regardless of whether they were infected by a fully susceptible or a low-level-resistant strain. Resistance did not emerge during therapy. For the more resistant of the two low-level-resistant strains, methicillin was as effective as nafcillin. Nafcillin was ineffective against endocarditis caused by a truly methicillin-resistant strain, and resistance emerged on therapy. The low-level-resistant strains did not produce the low-affinity penicillin-binding protein 2a that is associated with methicillin resistance and did not contain DNA that hybridized with probes that recognized the methicillin resistance determinant. Low-level resistance in S. aureus is a phenomenon that is biochemically and genetically distinct from true methicillin resistance. These strains actually are susceptible to beta-lactam antibiotics. The clinical problem posed by these strains is not a therapeutic one but, instead, one of how to differentiate them from those that are truly methicillin resistant.

Animals↗
PubMed1986

Continuous human glioma-derived cell lines UC-11MG and UC-302MG. Morphologic, immunocytochemical and chromosomal characterization.

Two continuous human glioma-derived cell lines, UC-11MG and UC-302MG were established in our laboratory. Both cell lines persistently showed cytologic features similar to those of their respective original tumors. UC-11MG expressed glial fibrillary acidic protein (GFAP) and S-100 protein. The cell lines were negative for factor VIII related antigen (FVIII/RAg) and positive for fibronectin and neuronal specific enolase (NSE). Electron microscopic studies of UC-11MG revealed intermediate filament; filopodia and pinocytic vesicles were present in both lines. Dibutyryl cAMP (dB-cAMP) caused inhibition of growth and marked shift in the morphology of UC-302MG toward spindle cells. The cytologic appearance of UC-11MG treated with dB-cAMP was altered less, but cells showed a stronger GFAP expression, with 'cable' formation. Doubling time was 41.0 +/- 6.4 hours for UC-11MG and 43.7 +/- 6.6 hours for UC-302MG. The karyotypes of both cell lines were aneuploid with chromosomal derangement and markers characteristic for each line.

Bucladesine↗
PubMed1984

In-vitro synergy testing of triple antibiotic combinations against Staphylococcus epidermidis isolates from patients with endocarditis.

In-vitro synergy testing was performed against ten blood or valve isolates of Staphylococcus epidermidis taken from patients with endocarditis. A three-dimensional microtitre checkerboard method was used for evaluation of vancomycin-rifampicin-gentamicin. The triple combination of vancomycin plus rifampicin plus gentamicin was found to be synergistic in 70% of the isolates. Vancomycin plus rifampicin was not synergistic. Oral agents including dicloxacillin, rifampicin, and fusidic acid were also evaluated. Four methicillin-resistant isolates were relatively resistant to dicloxacillin (MIC greater than 0.79 mg/l) but all four isolates were susceptible to fusidic acid alone and rifampicin alone. The triple combination of dicloxacillin plus fusidic acid plus rifampicin was found to be synergistic in 50% of the isolates and generally superior to any two-drug combination raising the possibility of an effective oral combination of antibiotics.

Anti-Bacterial Agents↗
PubMed1977

Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin.

Rabbits with left-sided endocarditis due to Pseudomonas aeruginosa were treated with a high dose (7.5 mg/kg) of gentamicin for six days, a low dose (5 mg/kg) of gentamicin for six days or two weeks, carbenicillin (400 mg/kg) for six days or two weeks, or a combination of the lower dose of gentamicin and carbenicillin (400 mg/kg) for six days or two weeks. Sterilization of cardiac vegetations was accomplished more effectively in rabbits given the higher dose of gentamicin for six days (44% with sterilized vegetations) or combination therapy for 14 days (64%) than in rabbits given the lower dose of gentamicin or carbenicillin alone for two weeks (23.5% and none, respectively). Combination therapy for two weeks prevented relapse in all of six treated rabbits that were followed after treatment; in contrast, all four animals treated with carbenicillin and four of six animals treated with the lower dose of gentamicin relapsed after two weeks of treatment. Levels of creatinine in serum became elevated in four of nine rabbits that received gentamicin along for two weeks. Therapeutic success was associated with a synergistic antibiotic combination, a peak bactericidal titer in serum of greater than or equal to 1:16, and a high level of gentamicin in serum.

Animals↗
PubMed1976

Experimental endocarditis due to Pseudomonas aeruginosa. I. Description of a model.

Rabbits with sterile, right ventricular cardiac vegetationss were challenged with Staphylococcus aureus and serum-susceptible or -resistant isolates of Pseudomonas aeruginosa. None of the rabbits challenged with serum-susceptible P. aeruginosa died or had greater than 10(2) colony-forming units (cfu)/g cultured from vegetations two weeks later. In contrast, 78% of animals challenged with serum-resistant P. aeruginosa died within three weeks, and 74% sacrificed at three days had organisms cultured from vegetations. All of the animals challenged with S. aureus died, and all had greater than 10(8) cfu of P. aeruginosa/g in vegetation tissue at three days. There was a significantly greater number of organisms (P less than 0.001) in the vegetations of animals dying of S. aureus infection than in those of animals with P. aeruginosa endocarditis (mean, 10(9.6) vs. 10(7.5) cfu/g, respectively). Left-sided endocarditis was produced in 100% of rabbits injected with serum-resistant P. aeruginosa. These models could be used for studies of the pathogenesis and therapy of P. aeruginosa endocarditis.

Animals↗
PubMed1976

Pulmonary sporotrichosis: Treatment with miconazole.

Intravenous miconazole, an investigational, broad-spectrum, antifungal imidazole drug, was clinically effective when used for the first time in a patient with life-threatening sporotrichosis. Miconazole was used after drug resistance and treatment failure occurred in a patient with extensive, cavitary, pulmonary infection with Sporotrichum schenckii. He had first been treated with amphotericin B, and then with amphotericin B and flucytosine in combination. Side effects of miconazole included itching, diarrhea, and phlebitis. Clinical improvement occurred despite plasma concentrations below those needed for complete inhibition of the patient's organisms in vitro.

Amphotericin B↗
PubMed1975

Therapy of Pseudomonas aeruginosa infections with tobramycin.

The efficacy of tobramycin in doses of 2.7 to 5.6 mg/kg per day in 29 courses of therapy in 25 hospitalized patients with serious Pseudomonas aeruginosa infections was studied. Eighty-three percent of the P. aeruginosa strains showed zones of inhibition of 16 mm or more around a 10-mug tobramycin disk in the Bauer-Kirby disk method. Tobramycin minimal inhibitory concentration ranged from <0.05 to 1.5 mug/ml (microtiter twofold dilution method); for gentamicin they ranged from 0.05 to 6.2 mug/ml; corresponding geometric means were 0.19 and 0.49 mug/ml. Therapy was given for a median of 10 days (mean 19, range 1 to 83). The clinically satisfactory response rate for the 29 courses of therapy was 52%: critically ill, 44%; seriously ill, 50%; moderately ill, 80%. The response rates for various sites of infection were bone and cartilage, 100%; urinary tract infection, 56%; wound, 50%; respiratory tract, 67%; septicemia, 40%; abscess, 0%; burns, 44%. No adverse reactions were seen. Serum concentration (mug/ml +/- standard deviation) of tobramycin determined by an agar-well plate method, were 4.81 +/- 2.17 (1 h); 3.24 +/- 1.43 (2 h); 2.35 +/- 1.30 (4 h); and 1.40 +/- 1.09 (8 h). Tobramycin appears to be as effacacious as gentamicin in the treatment of serious P. aeruginosa infections and has a theoretical advantage of lower minimal inhibitory concentration for P. aeruginosa. The data suggest that, for life-threatening infections, dosages of tobramycin may need to be increased over those used in this study.

Adolescent↗
PubMed1975

Bedside pulmonary arteriography.

A new technique of bedside pulmonary arteriography is described, in which small volumes of contrast material are injected manually in order to obtain segmental arteriograms in patients who are too ill to undergo conventional pulmonary angiography. This method is safe and effective and can provide information which is useful in the management of certain critically ill patients.

Angiography↗
PubMed1974

Long term pulmonary artery pressure monitoring in the management of the critically ill.

Detailed experience during prolonged pulmonary artery pressure monitoring (up to 19 days) in 86 seriously ill patients is reviewed. Strict adherence to a protocol developed for insertion and maintenance of Swan-Ganz catheters resulted in successful catheterization of the pulmonary artery in nearly 100% of patients with minimal morbidity. Several technical problems associated with the use of this catheter-monitoring system are described, excessive balloon inflation with resultant misleading, spuriously high pressure measurement being one of the most serious. Most technical problems are avoidable. In the majority of critically ill patients both central venous and pulmonary artery diastolic pressures proved to be in-accurate estimates of pulmonary artery wedge pressure (PAW). PAW was a useful adjunct in the assessment of intravascular volume and hemodynamic alterations in these patients. The Swan-Ganz catheter serves for other functions including collection of mixed venous blood for cardiac output determination and injection of contrast material for small vessel angiography. Measurement of pulmonary artery wedge pressures should be routinely included in the sequential hemodynamic evaluation of most patients sufficiently ill to be hospitalized in an intensive care unit.

Adolescent↗