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Biomedical subjects

G J Small

Publications and source records attributed to G J Small.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pyrethroid resistance in German cockroaches (Dictyoptera: Blattelidae): resistance levels and underlying mechanisms.

Thirty strains of Blattella germanica (L.) reported to be pyrethroid resistant were collected from three continents. Greater than 2-fold resistance to the pyrethroids cyfluthrin, fenvalerate, cypermethrin, and lambda cyhalothrin appeared in 15 of these strains. Twelve of these strains were also resistant to chlorpyrifos and propoxur. All the field strains tested were heterogeneous with regard to resistance. Possible resistance mechanisms detected in these populations included elevated levels of cytochrome P450, general esterase and glutathione S-transferase, and nerve insensitivity (kdr-type resistance). The elevated esterases and oxidase-based resistance were the most prevalent; 11 and 10 strains, respectively, had evidence of these mechanisms. Resistance was synergized by piperonyl butoxide in some strains. In some strains, elevated esterases, although present, were primarily correlated with organophosphate resistance. Pyrethroid insecticides may still be effective against many of these populations because of the low levels of resistance detected. However, potential exists for more serious resistance problems to develop if only pyrethroids are used. Because many of these strains are already resistant to organophosphorus and carbamate insecticides, prospects for the future chemical control of these populations must be carefully considered.

Animals↗
PubMed1992

Separation and identification of DNA-carcinogen adduct conformers by polyacrylamide gel electrophoresis with laser-induced fluorescence detection.

We have developed a separation protocol utilizing high-resolution polyacrylamide gel electrophoresis (PAGE) to isolate stable anti-benzo[a]pyrene diol epoxide adducts of oligodeoxynucleotides. Both enantiomers produced multiple adduct species. The distribution of adduct types could be quantitated by densitometry of autoradiograms or Cerenkov counting of eluted oligomers modified by anti-BPDE isomers. Laser-induced fluorescence (LIF) spectra of eluted adducts at 4.2 K (fluorescence line-narrowing spectroscopy) and 77 K revealed that bands corresponded to pure conformers of pyrene chromophore. Carcinogen-modified oligodeoxynucleotides were single-stranded, but there were often considerable stacking interactions between the pyrenyl residues and the oligonucleotide bases, indicating that electrophoresed oligomers were single-stranded but in a native, versus random coil, conformation. The ability to identify and quantitate adducts by PAGE-LIF, coupled with the high resolution and sensitivity of both techniques, makes PAGE and LIF in tandem a potentially powerful tool in the study of chemical carcinogenesis or other ligand-DNA interactions.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Insecticide resistance gene frequencies in Anopheles sacharovi populations of the Cukurova plain, Adana Province, Turkey.

In Turkey, the mosquito Anopheles sacharovi has been under field selection pressure sequentially with DDT, dieldrin, malathion and pirimiphosmethyl over a period of 30 years for the purpose of malaria control. In 1984, the field population of An.sacharovi in the malarious Cukurova plain of Adana Province contained an altered acetylcholinesterase-based resistance gene giving broad spectrum resistance against organophosphorus and carbamate insecticides. The cross-resistance spectrum from this mechanism conferred resistance to malathion but not to the organophosphorus insecticide pirimiphos-methyl. Over the 6 years that pirimiphos-methyl has been applied for malaria vector control in this area, the frequency of the altered acetylcholinesterase resistance gene has declined, although in 1989 and 1990 it was still present at measurable frequencies in An.sacharovi from Cukurova. In addition to the acetylcholinesterase resistance mechanism there is evidence of an increased level of glutathione S-transferase in some of the An.sacharovi populations tested. This is known to be correlated with DDT resistance in other anophelines. In Turkish An.sacharovi, DDT resistance and elevated glutathione S-transferase occur in the same populations at similar frequencies. The continued prevalence of resistance to DDT and dieldrin, long after the 1971 cessation of DDT spraying for malaria control in Turkey, suggests that the DDT resistance gene has insufficient reduced fitness associated with it to have been lost from the field population during the past two decades. The implications of the slow decline in resistance gene frequencies in this field population are discussed in relation to mathematical models for managing resistance.

Acetylcholinesterase↗
PubMed1991

Malathion and pyrethroid resistance in Culex quinquefasciatus from Cuba: efficacy of pirimiphos-methyl in the presence of at least three resistance mechanisms.

Use of malathion for mosquito control in Cuba for 7 years up to 1986 has selected for elevated non-specific esterase and altered acetylcholinesterase (AChE) resistance mechanisms in populations of the pest mosquito Culex quinquefasciatus Say. These mechanisms are still present in relatively high frequencies in the Havana area, despite the replacement of malathion by pyrethroid insecticides for the last 3 years in the mosquito control programme. Samples of Culex quinquefasciatus populations from within a 100 km radius of Havana had high levels of resistance to malathion and lower levels of resistance to propoxur, but there was little or no cross-resistance to the organophosphorus insecticide pirimiphos-methyl. Selection with malathion for twenty-two consecutive generations in the laboratory increased the level of malathion resistance to 1208-fold and propoxur level to 1002-fold, but the maximum level of pirimiphos-methyl resistance was only 11-fold. Pirimiphos-methyl is still operationally effective, despite the resistance mechanisms segregating, so this insecticide if used for control is unlikely to select either of the known resistance factors directly in the field population. Since 1986, pyrethroids have been used extensively, and low levels of pyrethroid resistance were detected in two of five field population samples tested. Malathion selection did not increase the level of pyrethroid resistance, which indicates that one or more distinct pyrethroid resistance factors are now being selected in the field populations of Culex quinquefasciatus.

Aerosols↗
PubMed1990

Protection against mucoid Pseudomonas aeruginosa in rodent models of endobronchial infections.

Chronic endobronchial infection with mucoid Pseudomonas aeruginosa accounts for much of the morbidity and mortality in patients with cystic fibrosis (CF). Reduced morbidity is observed when infection is absent. Clinical investigations have implicated opsonizing antibody specific for the mucoid exopolysaccharide (MEP) surrounding these bacteria as a potential immunologic protective mechanism, whereas nonopsonizing antibody to MEP is not protective. Mice and rats immunized with doses of MEP that elicited opsonizing antibody had reduced levels of infection compared with nonimmune controls after intratracheal challenge with mucoid P. aeruginosa enmeshed in agar beads. Doses of MEP that elicited nonopsonizing antibody were not protective. Parallel experiments in which passive transfer of polyclonal and monoclonal opsonizing and nonopsonizing antibody were used yielded similar results. These data indicate that MEP-specific opsonizing antibody can protect against chronic P. aeruginosa infection in this model of disease.

Animals↗
PubMed1990

Fluorescence line-narrowing spectrometry: a versatile tool for the study of chemically initiated carcinogenesis.

An important initiating step in the induction of tumors is believed to be the covalent binding of an active carcinogenic species to a cellular macromolecule, e.g. DNA. Therefore, a spectroscopic technique which allows for positive identification of the intact (macromolecular) DNA adduct and/or isolated damaged nucleosides/nucleotides is highly desirable. It is shown that fluorescence line-narrowing spectroscopy (FLNS) is a rapid, versatile, highly sensitive and selective analytical technique, which can be used directly to characterize DNA adducts and isolated nucleosides. FLNS possesses sufficient resolution to distinguish between the major DNA adducts derived from different enantiomers of benzo[a]pyrene diol-epoxide (BPDE). With the present limit of detection (approximately 1 adducted base per 10(8) normal base pairs for 100 micrograms of DNA), the technique is applicable to in vivo samples. Analysis of liver DNA from fish exposed to benzo[a]pyrene (BP) (100 mg BP/kg fish) showed that a major DNA adduct is derived from syn-BPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1988

Enhancement of sensitivity of fluorescence line narrowing spectrometry for detection of carcinogen-DNA adducts.

Fluorescence line narrowing (FLN), is a method by which highly characteristic spectra have been obtained for a large number of polycyclic aromatic hydrocarbon (PAH)-DNA adducts and is well suited for the analysis of exposures to complex mixtures of PHA. The basic method is described and recent improvements discussed which overcome one of the major limitations of the method to its wider application to biological samples, that is its sensitivity.

Animals↗
PubMed1987

Passive immune therapy for experimental Pseudomonas aeruginosa pneumonia in the neutropenic host.

Studies were conducted in guinea pigs, myelosuppressed by cyclophosphamide, for determination of whether passive immune therapy for Pseudomonas aeruginosa pneumonia would be useful in the setting of neutropenia. Groups of infected animals (14 per group) were treated with a single intravenous infusion of hyperimmune IgG antibody to P. aeruginosa (PA-IGIV; 500 mg/kg), tobramycin (1.7 mg/kg per 8 hr), ticarcillin (120 mg/kg per 6 hr), or combinations of these regimens. Control groups received intravenous albumin solution. Survival rates were 0% with albumin only, 0% with PA-IGIV, 43% with tobramycin (P less than .05), 86% with tobramycin plus PA-IGIV (P less than .05 vs. tobramycin alone), 7% with ticarcillin, and 43% with ticarcillin plus PA-IGIV (.05 less than P less than .10 vs. ticarcillin alone). Additive intrapulmonary killing of P. aeruginosa and prevention of bacteremia were observed in animals treated with tobramycin plus PA-IGIV compared with either treatment alone. Thus, passive immune therapy for P. aeruginosa pneumonia may be useful in the neutropenic host, but only when used in conjunction with antimicrobial agents.

Agranulocytosis↗
PubMed1986

Relation of cytosolic calcium to the microbicidal activation of blood monocytes by recombinant gamma interferon.

Oxygen metabolism and calcium ion (Ca++) handling in blood monocytes were greatly affected by treatment with recombinant gamma interferon (rIFN-gamma). Incubating the monocytes with rIFN-gamma resulted in increased basal production of superoxide anion, as well as a significantly enhanced respiratory burst in response to concanavalin A (Con A). A concomitant increase in microbicidal activity against Listeria monocytogenes was observed, and cell membrane permeability to Ca++ was enhanced by treatment with rIFN-gamma. Con A stimulation was also associated with acute rises in cytosolic-free calcium, and these calcium transients were greatly augmented in cells pretreated with rIFN-gamma. The enhanced respiratory burst and the increased calcium transients were completely neutralized by a monoclonal antibody to rIFN-gamma. Furthermore, enhancement of the respiratory burst and calcium transients occurred in a parallel dose-response range for rIFN-gamma. Blocking the intracellular release of calcium into cytosol by TMB-8 abrogated the capacity of rIFN-gamma to enhance the monocyte respiratory burst. Thus, not only was rIFN-gamma treatment of monocytes associated with altered calcium metabolism, but calcium from intracellular pools was essential to the expression of this activated state during Con A stimulation.

Blood Bactericidal Activity↗
PubMed1986

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia.

The therapeutic activity of ciprofloxacin, enoxacin, and ofloxacin was evaluated in guinea pigs with acute and chronic experimental Pseudomonas aeruginosa pneumonia. Intratracheal instillations of P. aeruginosa resulted in fatal pneumonia in all untreated animals within 36 h. Among treatment groups (80 mg/kg [body weight] per day), cumulative survival rates were: 47%, ciprofloxacin; 55%, enoxacin; and 42%, ofloxacin. These rates were not significantly different. Intrapulmonary killing of P. aeruginosa was equivalent 3 h after a single dose of ciprofloxacin or ofloxacin (20 mg/kg) or enoxacin (40 mg/kg). The combination of ciprofloxacin with azlocillin, ceftazidime, or tobramycin did not increase the efficacy of intrapulmonary killing of P. aeruginosa over that of ciprofloxacin alone. A chronic, nonfatal bronchopneumonia was induced in guinea pigs by intratracheal instillation of microscopic agar beads impregnated with a mucoid strain of P. aeruginosa. Compared with no treatment, ciprofloxacin and enoxacin produced greater than or equal to 99.9% intrapulmonary killing, and ofloxacin sterilized the lungs completely, after 4 days of treatment. In no quinolone-treated animal did resistant strains of P. aeruginosa emerge during 4-day treatment periods. In further studies with the chronic model, oral and parenteral ciprofloxacin treatment were found to be equivalent in efficacy. We conclude that several quinolone derivatives may be effective for the treatment of P. aeruginosa pneumonia and that combinations of quinolones with beta-lactams or aminoglycosides may not increase efficacy against P. aeruginosa pneumonia.

Animals↗
PubMed1986

Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia.

A human immunoglobulin G preparation, enriched in antibodies to lipopolysaccharide (LPS) Pseudomonas aeruginosa antigens (PA-IGIV) and murine monoclonal antibodies (MAb) to P. aeruginosa Fisher immunotype-1 (IT-1) LPS antigen and outer membrane protein F (porin), were evaluated for therapeutic efficacy in a guinea pig model of P. aeruginosa pneumonia. The concentration of antibodies to IT-1 LPS was 7.6 micrograms/ml in PA-IGIV and 478 micrograms/ml in the IT-1 MAb preparation. No antibody to IT-1 was detected in MAb to porin. For study, animals were infected by intratracheal instillation of IT-1 P. aeruginosa and then treated 2 h later with intravenous infusions of PA-IGIV, IT-1 MAb, or porin MAb. Control groups received intravenous albumin, and routinely died from pneumonia. Both PA-IGIV (500 mg/kg) and IT-1 MAb (greater than or equal to 2.5 mg/kg) treatment resulted in increased survival (P less than 0.01 to 0.001), and also improved intrapulmonary killing of bacteria. Porin MAb failed to protect from fatal pneumonia. IT-1 MAb treatment produced more survivals than did PA-IGIV treatment but only at dosages of MAb resulting in serum antibody concentrations greater than those achieved with PA-IGIV. PA-IGIV and IT-1 MAb demonstrated in vitro and in vivo (posttreatment guinea pig serum) opsonophagocytic activity for the IT-1 challenge strain. However, the polyclonal preparation required complement, whereas the MAb did not. We conclude that passive immunization with polyclonal hyperimmune P. aeruginosa globulin or with MAb to LPS antigens may be useful in the treatment of acute P. aeruginosa pneumonia. The relative efficacies of such preparations may be limited, however, by their type-specific LPS antibody concentrations.

Absorption↗
PubMed1984

Fluorescence-line-narrowed spectra of polycyclic aromatic carcinogen-DNA adducts.

The laser excited fluorescence-line-narrowed spectrum of DNA modified with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), the ultimate carcinogenic metabolite of benzo[a]pyrene (BP), has been obtained in a water-glycerol-ethanol glass at 4.2 K. The spectrum was well resolved and highly characteristic of the chromophore. Comparisons were made between the spectrum of this modified DNA and the isolated deoxyguanosine-BPDE adduct and a series of other 7,8,9,10-tetrahydro-BP (THBP) derivatives. 9-Hydroxy-BP 4,5-oxide, which is also involved in the binding of BP to DNA, and THBP have very similar conventional broadband fluorescence spectra. However, the fluorescence-line-narrowed spectra of their derivatives were readily distinguishable either as individual components or as mixtures.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1984

Comparative activities of ciprofloxacin, ticarcillin, and tobramycin against experimental Pseudomonas aeruginosa pneumonia.

The therapeutic efficacy of ciprofloxacin, an investigational quinoline derivative, was compared with those of ticarcillin and tobramycin in guinea pigs with experimental Pseudomonas aeruginosa pneumonia. Guinea pigs challenged with tracheal instillations of 10(8) CFU of P. aeruginosa developed acute pneumonia, for which survival rates were: controls, 0%; ticarcillin treatment, 37%; ciprofloxacin treatment, 57%; and tobramycin treatment, 69%. Intrapulmonary killing of P. aeruginosa was greater (P less than 0.05) in animals treated with ciprofloxacin or tobramycin than in groups treated with ticarcillin. A more chronic, nonfatal form of bronchopneumonia caused by P. aeruginosa was induced with agar beads impregnated with bacteria for pulmonary challenge. In this model, ciprofloxacin treatment resulted in significantly (P less than 0.001) greater intrapulmonary killing than did any other therapy. These data suggest that ciprofloxacin may be useful in the treatment of acute and more-chronic forms of pulmonary infection caused by P. aeruginosa.

Animals↗