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Biomedical subjects

B R Andersen

Publications and source records attributed to B R Andersen.

At least 19 recordsLinked to original sources
PubMed1979

Defective initiation of oxidative metabolism in polymorphonuclear leukocytes.

The polymorphonuclear leukocytes of a two-year-old boy who had multiple episodes of bacterial infections demonstrated defective oxidative metabolism with phagocytic, but not with soluble (non-phagocytic), metabolic stimuli. We used a chemiluminescence assay to examine the patient's polymorphonuclear leukocyte responses to numerous particulate and soluble stimuli. The patient's polymorphonuclear leukocytes had substantially depressed chemiluminescent responses during phagocytosis of opsonized particles (latex, pneumococci, pseudomonas, streptococci and zymosan); however, we observed normal chemiluminescent responses when these leukocytes were stimulated with soluble agents (sodium fluoride, concanavalin A, cytochalasin E, calcium ionophore A23187 or phorbol myristate acetate). Polymorphonuclear leukocyte oxygen consumption and superoxide production were impaired during phagocytosis, even though phagocytosis was normal. In addition to the metabolic defect, this patient's polymorphonuclear leukocytes had depressed chemotactic and bactericidal activities. This study provides evidence that polymorphonuclear leukocytes have more than one mechanism for initiating oxidative metabolism.

Blood Bactericidal Activity↗
PubMed1979

Light generation with Fenton's reagent. Its relationship to granulocyte chemiluminescence.

A simple chemical system consisting of FeSO4 and H2O2 (Fenton's reagent) was shown to emit light (chemiluminescence). The addition of tryptophan to the reaction markedly enhanced light production. Very little chemiluminescence was observed when H2O2 was omitted from the reaction and when ferric, instead of ferrous, ions were used. Hydroxyl radical (OH.) and singlet oxygen (1 deltagO2) quenchers suppressed chemiluminescence of the FeSO4 + tryptophan + H2O2 system; and, deuterium oxide (2H2O) enhanced chemiluminescence of both FeSO4 reactions. These observations suggest that a radical chain reaction involving both OH. and 1 deltag O2 is responsible for the chemiluminescent reactions. Six iron-containing proteins, some of which are located within granulocytes, all emitted light in the presence of H2O2. Since iron and H2O2 are present in metabolically stimulated granulocytes, it is likely that chemiluminescent reactions similar to the ones demonstrated in this study account for part of the chemiluminescence of activated granulocytes.

Chemical Phenomena↗
PubMed1979

Failure of trimethoprim/sulfamethoxazole in invasive Nocardia asteroides infection.

A case of pulmonary nocardiosis occurred with progressive involvement of the pleura, pericardium, mediastinum, and sternum. Surgical resection and drainage procedures followed by administration of the drug combination, trimethoprim/sulfamethoxazole, over a six-month period led to clinical recovery. Discontinuation of drug therapy, however, was followed by relapse and further invasion by the same organism. A literature survey of Nocardia asteroides infections treated with trimethoprim/sulfamethoxazole disclosed that posttreatment follow-up is often too brief or unknown, making the ultimate success of therapy uncertain.

Administration, Oral↗
PubMed1978

Chemically shifted singlet oxygen spectrum.

The estimated light emission spectrum was determined for a singlet oxygen (1O2)-producing system, NaOCl + H2O2, alone and in the presence of tryptophan and bovine serum albumin. Tryptophan and bovine serum albumin caused a decrease in the red emission of 1O2 and an increase in the amount of shorter wavelength light. This effect was due to chemiluminescence rather than fluorescence. Arachidonic acid caused a similar spectral shift, while guanosine demonstrated a late chemiluminescent reaction of predominantly short wavelength light in the presence of 1O2.

Hydrogen Peroxide↗
PubMed1978

Use of a unique chemiluminescence spectrometer in a study of factors influencing granulocyte light emission.

Factors contributing to variability in chemiluminescence (CL) measurements of phagocytizing granulocytes were identified and controlled. Observed CL was decreased by light quenching caused by red blood cells, hemoglobin, phagocytizable particles, and granulocytes. Increases in CL were achieved by opsonization with heat labile and heat stable (antibody) serum factors, reaction temperatures in the range of 37-40 degrees C, and mixing. The effects of controlled temperature variation and mixing were studied with a chemiluminescence spectrometer uniquely designed for such studies. Features of this spectrometer which make it more suitable than the previously employed scintillation spectrometers for the observation of granulocyte and other chemiluminescent systems include; (1) the ability to measure CL immediately upon reaction initiation; (2) simplicity of photomultiplier tube exchange; and (3) built-in optical filter holders for spectral analysis.

Animals↗
PubMed1978

Chemiluminescence of human and canine polymorphonuclear leukocytes in the absence of phagocytosis.

Polymorphonuclear leukocytes (PMNs) have increased oxidative metabolism during phagocytosis and emit light (chemiluminescence, CL) as a result of metabolic activation. The present study examined PMN CL in the absence of phagocytosis using sodium fluoride (NaF), a nonparticulate agent and known stimulator of cellular oxidative metabolism. Normal human and canine PMNs were assayed in a CL spectrometer which permitted continuous sample mixing and constant temperature regulation during CL measurement. PMNs treated with 20 mM NaF demonstrated maximum CL responses of 10,000-20,000 cpm above background, 13-17 min after addition of NaF at 37 degrees C. Temperature regulation of reaction mixtures was found to be a critical factor in assaying PMN CL responses to NaF, because a small decrease in temperature (i.e. 1.5 degrees C) substantially depressed and delayed the CL response. Superoxide anion production correlated closely with CL responses in NaF-treated human PMNs. CL responses were completely suppressed in the presence of the oxidative metabolic inhibitors, iodoacetamide, and N-ethylmalemide; and were partially suppressed in the presence of either superoxide dismutase or sodium azide.CL responses of NaF-treated PMNs were significantly lower than responses generated by PMNs phagocytizing opsonized yeast. When NaF was evaluated for its effect on light generation from a singlet oxygen dependent CL reaction, it was found that NaF did not quench singlet oxygen light. This study demonstrates that PMN CL can occur in the absence of phagocytosis, and it proposes that a nonphagocytic PMN CL assay may be useful in evaluating leukocyte metabolic defects.

Animals↗
PubMed1978

Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host.

An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

Animals↗
PubMed1977

Chemiluminescence spectra of human myeloperoxidase and polymorphonuclear leukocytes.

The light emission spectra of myeloperoxidase-H2O2-Cl- and phagocytizing polymorphonuclear leukocytes were estimated by a computer simulation technique by using light transmittance data from nine band-pass filters. No shift in the chemiluminescence spectrum of either system was observed during the course of the reactions, suggesting that the light-generating mechanisms remain constant after their initiation. Transmittances were virtually identical for both myeloperoxidase-H2-O2-Cl- and polymorphonuclear leukocyte reactions, suggesting that the light-generating mechanisms are identical and leading to the estimation of nearly identical spectra. Both spectra were broad, with maximum light emission near 570 nm.

Computers↗
PubMed1977

Organ distribution of canine leukocytes labeled with 99mTc-sulfur colloid.

Previous reports have shown that scintigraphic localization of acute inflammation can be achieved using autologous leukocytes labeled in vitro with 99mTc-sulfur colloid (TcSC). The technique is limited, however, by a marked accumulation of radioactivity in the lungs and liver of normal animals. A modified procedure was developed using preparations of TcSC of small particle size to label blood leukocytes in vitro. Markedly decreased levels of lung and liver radioactivity and elevated levels of blood radioactivity were found after intravenous infusion of autologous canine leukocytes labeled by this method. These leukocytes could be used to image areas of acute inflammation resulting from induction of septic or sterile venous thrombi.

Animals↗
PubMed1976

Value of granulocyte examination for bacteria.

Granulocytes from patients with suspected bacteremia and from dogs with staphylococcal bacteremia were examined by light microscopy for the presence of intracellular inclusions that resembled microorganisms. Quantitative blood cultures were done at the same time. Few granulocytic inclusions were observed during a two-hour screening period even when high levels of bacteremia were present. There was no correlation between the number of inclusions and the quantitative blood culture data. The inclusions appear to be artifacts of the staining procedure. This technique has questionable value in the diagnosis of bacteremia and may be misleading.

Animals↗
PubMed1976

Evaluation of type-specific and non-type-specific pseudomonas vaccine for treatment of pseudomonas sepsis during granulocytopenia.

The protective role of serotype-specific and non-type-specific active immunity against Pseudomonas aeruginosa infection was assessed in granulocytopenic dogs. Dogs were preimmunized with either specific serotype 6 vaccine (SI) or nonspecific serotype 3 vaccine (NSI) and challenged intravenously with 10(7) viable serotype 6 P. aeruginosa during granulocytopenia. Control dogs (C) having insignificant anti-pseudomonas antibody levels were also tested. Results showed: (i) significant increase in survival of SI dogs (P less than 0.05) compared to C and NSI dogs, with no significant difference between C and NSI animals; (ii) lower febrile responses in SI dogs; and (iii) markedly reduced bacteremia in SI dogs compared to C and NSI animals. SI dog sera from survivor animals did not kill the infecting pseudomonas strain in vitro. The study demonstrated that type-specific immunity to P. aeruginosa induced by active immunization is effective in protection against pseudomonas during granulocytopenia and that non-type-specific immunity offers no cross-reactive protection. The findings suggest that the reticuloendothelial system in conjunction with specific immunity constitute an important defense against pseudomonas infections.

Agranulocytosis↗
PubMed1976

Passive immunity against pseudomonas sepsis during granulocytopenia.

Specific passive immunity against Pseudomonas aeruginosa sepsis was assessed in granulocytopenic dogs. Dogs were infused with either normal or antipseudomonas immune plasma 24 h before pseudomonas challenge. They were challenged intravenously with 10(7) serotype 6 P. aeruginosa during granulocytopenia. Treatment was evaluated by observation of survival periods, febrile responses, type 6 pseudomonas antibody titers, and quantitative cultures of blood and tissues. The results demonstrated that passively immunized dogs did not survive infection. Both normal-plasma and immune-plasma recipients had bacteremia at death, with median values of 980 and 470 pseudomonas per ml of blood, respectively. All dogs had marked febrile responses 24 h after pseudomonas challenge and had high concentrations of pseudomonas in their lung tissue at death, with median values of 10(8) pseudomonas per g of wet tissue weight. After plasma infusion, immune-plasma recipients had high concentrations of anti-pseudomonas antibody, with total antibody titers ranging from 256 to 1,024 and a median value of 1,024. These titers were comparable to titers attained in a previous study from our laboratory using active immunization with pseudomonas lipopolysaccharide vaccine, where the median total anti-pseudomonas antibody titer was 2,048. Actively immunized animals, however, were significantly protected against pseudomonas sepsis and had prolonged survival periods and prevention of bacteremia. The present study demonstrates that circulating type-specific antibody is not solely responsible for the protection afforded to granulocytopenic dogs actively immunized against pseudomonas.

Agranulocytosis↗
PubMed1976

Effect of bone marrow suppression on granulocyte opsonin levels.

Levels of serum opsonin for neutrophilic granulocytes were measured in dogs made neutropenic by cyclophosphamide administration. Heat-labile opsonin became elevated within 24 hr following cyclophosphamide (P less than 0.005) and remained elevated over the 4-5 day period of observation (P less than 0.005). In contrast, heat stable opsonin was not significantly effected. Bone marrow suppression by X-ray and busulfan also caused serum opsonin levels to increase. Changes in the levels of IgG, C3, and total hemolytic complement during the course of bone marrow suppression did not correlate with the granulocyte opsonin levels. These findings suggest that serum granulocyte opsonin levels respond to bone marrow suppression and may provide an improved environment for the function of transfused granulocytes.

Agranulocytosis↗
PubMed1976

Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs.

An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia.

Agranulocytosis↗