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Biomedical subjects

C Erickson

Publications and source records attributed to C Erickson.

At least 19 recordsLinked to original sources

Emissions of sulfur trioxide from coal-fired power plants.

Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough to not cause opacity violations and acid deposition. Generally, a small fraction of sulfur (S) in coal is converted to SO3 in coal-fired combustion devices such as electric utility boilers. The emissions of SO3 from such a boiler depend on coal S content, combustion conditions, flue gas characteristics, and air pollution devices being used. It is well known that the catalyst used in the selective catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small fraction of sulfur dioxide in the flue gas to SO3. The extent of this oxidation depends on the catalyst formulation and SCR operating conditions. Gas-phase SO3 and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and wet scrubber), result in fine acidic mist, which can cause increased plume opacity and undesirable emissions. Recently, such effects have been observed at plants firing high-S coal and equipped with SCR systems and wet scrubbers. This paper investigates the factors that affect acidic mist production in coal-fired electric utility boilers and discusses approaches for mitigating emission of this mist.

Air Pollutants, Occupational↗

Epidermal powder immunization induces both cytotoxic T-lymphocyte and antibody responses to protein antigens of influenza and hepatitis B viruses.

Cytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5- to 2.5-microm gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice. EPI with hepatitis B surface antigen (HBsAg) and a synthetic peptide of influenza virus nucleoprotein (NP peptide) elicited antigen-specific CTL responses as well as antibody responses. In an in vitro cell depletion experiment, we demonstrated that the CTL activity against HBsAg elicited by EPI was attributed to CD8(+), not CD4(+), T cells. As controls, needle injections of HBsAg or the NP peptide into deeper tissues elicited solely antibody, not CTL, responses. We further demonstrated that EPI with inactivated A/Aichi/68 (H3N2) or A/Sydney/97 (H3N2) influenza virus elicited complete protection against a mouse-adapted A/Aichi/68 virus. In summary, EPI directly delivers protein antigens to the cytosol of the LCs in the skin and elicits both cellular and antibody responses.

Animals↗

Analysis of the heterogeneity of pO2 dynamics during photodynamic therapy with verteporfin.

Photodynamic therapy (PDT) with verteporfin provides a reliable way to destroy malignant tissues. Changes in the blood flow and oxygen partial pressure (pO2) during verteporfin-PDT were studied here in the tumor tissue of the rat mammary R3230Ac carcinoma model. Oxygen microelectrodes (6-12 microns tip diameter) were used to measure the transients locally within tumors during intravenous injection of 1.0 mg/kg verteporfin followed by irradiation 15 min later with 690 nm light at 200 mW/cm2, for a cumulative dose of 144 J/cm2. The observed changes in pO2 were heterogeneous and there was a difference in the response of low-pO2 regions relative to higher-pO2 regions. The change in pO2 in hypoxic tissue regions (pO2 < 8 mmHg) had acute pO2 loss after treatment, whereas the response in regions of higher pO2 (> 8 mm Hg) was more heterogeneous with some areas maintaining their pO2 value after treatment was completed. Blood flow measurements taken on a subset of the animals indicated a significant loss in flow during the initial light delivery that remained low after treatment, indicating some vascular stasis. The results suggest that hypoxic or poorly perfused vessels may be more susceptible to acute stasis than normoxic vessels in this treatment protocol.

Animals↗

The Nop60B gene of Drosophila encodes an essential nucleolar protein that functions in yeast.

The Cbf5 protein of Saccharomyces cerevisiae was originally identified as a low-affinity centromeric DNA-binding protein, and chf5 mutants have a defect in rRNA synthesis. A closely related protein from mammals, NAP57, is a nucleolar protein that coimmunoprecipitates with the nucleolar phosphoprotein Nopp140. To study the function of this protein family in a higher eukaryote that is amenable to genetic approaches, the gene encoding a Drosophila melanogaster homolog, Nop60B, was identified. The predicted Drosophila protein shares a high degree of sequence identity over a 380-residue region with both the mammalian and yeast proteins, and shares several conserved motifs with the prokaryotic tRNA pseudouridine 55 synthases. Nop60B RNA is found at high levels in nurse cells and in the oocyte, and is present throughout development. Nop60B protein is localized primarily to the nucleolus of interphase cells, and is absent from the chromosomes during mitosis. Nop60B mutants were generated and shown to be homozygous lethal. The Drosophila gene can rescue the lethal phenotype of yeast chf5 mutations, showing that the function of this protein has been conserved from yeast to Drosophila.

Amino Acid Sequence↗

Psychological disturbance differentially alters CD4+ and CD8+ leukocytes in the blood and intrathecal compartments.

To evaluate cellular changes in the intrathecal compartment in response to psychological stress, cerebrospinal fluid (CSF) and peripheral blood (PB) samples were obtained from rhesus monkeys under baseline and challenge conditions. Juvenile monkeys separated from their social companions overnight had elevated cortisol, increased polymorphonuclear (PMN), and fewer CD4+ and CD8+ leukocytes in PB. In contrast, in CSF there were more CD4+ and fewer CD8+ leukocytes, raising the CD4/CD8 ratio. Dexamethasone given intramuscularly caused similar hematological changes; i.e. neutrophilia and lymphocytopenia with fewer CD4+ and CD8+ leukocytes in PB. However, it did not induce similar changes in CSF, indicating that the stress-related shift of CD4+ leukocytes in the intrathecal compartment involves physiological processes beyond adrenocortical steroids.

Animals↗

Leukocyte trafficking in free-flowing cerebrospinal fluid of normal rhesus macaques (Macaca mulatta).

Cellular components in free-flowing cerebrospinal fluid (CSF) of normal rhesus macaques were characterized. Microscopic counting enumerated the total number of leukocytes, percentage of polymorphonuclear cells (PMN), leukocytes with nonspecific esterase (NSE), and those reducing nitro blue tetrazolium (NBT). Flow cytometric analysis further identified CD4, CD8, CD14, and CD20 positive leukocytes. These experiments established reliable techniques for evaluating cellular components in CSF from rhesus macaques and documented the difference in the CD4/CD8 ratio between peripheral blood (PB) and CSF compartments under normal physiological conditions.

Animals↗

Human lung air spaces: potential for MR imaging with hyperpolarized He-3.

Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.

Adult↗

Nonpolar environment of tryptophans in erythrocyte water channel CHIP28 determined by fluorescence quenching.

CHIP28 is an abundant water-transporting protein in erythrocytes, kidney proximal tubule, and other fluid-transporting tissues. To determine the environment of the four tryptophans in CHIP28, fluorescence spectra and quenching by polar and nonpolar compounds were measured in stripped human erythrocyte membranes containing CHIP28 and in proteoliposomes reconstituted with purified CHIP28; comparative studies were performed in membranes containing MIP26. Functional analysis showed that CHIP28 water permeability was not affected by the polar quenchers iodide and acrylamide nor the nonpolar n-anthroyloxy fatty acids (n-AF). The emission maximum of CHIP28 tryptophan fluorescence was at 324 +/- 2 nm and did not change with the addition of quenchers; the maximum for MIP26 was at 335 +/- 5 nm. There was weak quenching of CHIP28 tryptophan fluorescence by the polar compounds iodide and acrylamide, with Stern-Volmer constants of 0.13 and 0.71 M-1, respectively. HgCl2 inhibited water permeability by > 95% at 50 microM and quenched CHIP28 fluorescence reversibly by up to 70% with a biphasic concentration dependence; quenching by HgCl2 and acrylamide was not additive. The membrane-associated n-AF probes quenched CHIP28 fluorescence by up to 80% with the greatest quenching for n = 2 and 12; addition of HgCl2 or acrylamide after n-AF caused a small, anthroyloxy-position-dependent increase in quenching which was greatest at n = 6. These studies indicate that the tryptophans in CHIP28 are in a nonpolar, membrane-associated environment. Mathematical modeling of the n-AF results suggests that the tryptophans are clustered near the surface and center of the bilayer.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Porphyrin photosensitization of multi-drug resistant cell types.

The P388 murine leukemia and P388/ADR, a subline expressing the multi-drug resistance (MDR) phenotype, were examined with regard to the role of MDR as a determinant of responsiveness to photodynamic therapy in vitro. Mesoporphyrin was used as a model substrate. We found no differences in porphyrin accumulation nor transport alterations associated with exposure of P388/ADR cells to the verapamil analog DMDP. There was a significant correlation between photodamage to mitochondria vs loss of cell viability in both cell lines, and LD50 sensitizer levels were not significantly different in P388 vs P388/ADR. P388/ADR cells were partly resistant to porphyrin-catalyzed photodamage to amino acid transport, but this result was not associated with differences in sensitizer localization, as indicated by fluorescence studies. Moreover, photodamage to membrane transport was not associated with loss of viability. These studies suggest that cells which express the MDR phenotype are unlikely to be cross-resistant to photodynamic therapy.

Animals↗

Study of the separate and combined effects of the non-planar 2,5,2',5'- and the planar 3,4,3',4'-tetrachlorobiphenyl in liver and lymphocytes in vivo.

Polychlorinated biphenyls (PCBs) are a group of industrial chemicals that are widely distributed in the environment. Because these compounds occur as mixtures, studies of their possible interactive effects are essential for an understanding of the mechanism of the toxicity of these mixtures. For the determination of a possible interaction of the effects in vivo of 2,5,2',5'-tetrachlorobiphenyl (TCB) and 3,4,3',4'-TCB, rats were exposed to a single dose of diethylnitrosamine (DEN) and subsequently to 0.1 p.p.m. 3,4,3',4'-TCB and/or 10 p.p.m. 2,5,2',5'-TCB in the feed for 1 year. The two major targets of PCB toxicity, the liver and the peripheral blood, were examined after these treatments. TCB treatment after DEN exposure caused a predominance of increased placental glutathione S-transferase (PGST) and deficiencies of ATPase as preneoplastic markers in focal hepatic lesions. When 0.05% phenobarbital (PB) was administered after DEN exposure, the distribution of markers in altered hepatic foci (AHF) was essentially equal for increased PGST and gamma-glutamyltranspeptidase (GGT) and for ATPase deficiency. Many of these AHF also exhibited increased P450 b/e expression. Our results demonstrated that the two PCB congeners interacted in vivo to produce an increase in AHF that were PGST positive and ATPase negative. PGST-positive and ATPase-negative AHF correlated best with focal areas of P450 b/e expression. The combination of the two PCBs caused a greater than additive decrease in the total number of lymphocytes and antibody-producing B-cells. Also the thymocyte-dependent T-helper cells isolated from the animals receiving the combination of TCBs demonstrated a morphologically abnormal subpopulation. The results indicate that the interaction of 2,5,2',5'-TCB and 3,4,3',4'-TCB in vivo induced much greater toxicity and mutagenicity in peripheral lymphocytes and hepatocytes than treatment with either congener alone.

Animals↗

Prediction of intellectual deficits in children with acute lymphoblastic leukemia.

Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed.

Achievement↗

Ethanol and aging effects on movement initiation can be dissociated from general behavioral impairment using a high-speed lever-release task in rats.

An animal model of human reaction time was used to assess the effects of ethanol on reactive capacity (RC) as a function of age. Three doses of ethanol (0.5, 1.0 & 1.5 g/kg of 20% v/v, i.p.) were confirmed by gas chromatographic analysis of blood samples taken immediately following every behavioral test. Fisher 344 rats were trained to use their forepaws to hold down a lever until the onset of a buzzer and light that signalled impending foot shock, which occurred within 200-1000 msec of the stimulus. All rats were shaped to release the lever faster than 200 msec, which permitted them to avoid all shock under saline treatment. In the first experiment, only young adult rats (3-4 mos) were tested. Ethanol caused a dose-dependent impairment of RC. In a second experiment, rats aged 4, 12 and 24 mos were tested. As in previous work, RC was reduced by age. Ethanol caused a dose-dependent impairment of response speed (as indicated by the average of the fastest five RTs) that was exaggerated in the 24 mo-old rats. Ethanol also appeared to amplify the trial-by-trial variability in RC that was typical of the old rats under saline conditions. Nevertheless, if given enough time (1000 msec) most rats (except for a few in the oldest group) were able to avoid shock under ethanol as reliably as under saline conditions, even at the highest dose. Thus, ethanol specifically slowed reaction time while sparing memory and motivational and motor capacities required for success in this task. Both extensive practice and pre-test warm up sessions modified the effects of ethanol; however they did not do so differentially across ages.

Aging↗

Depletion of T cells from bone marrow for allogeneic transplantation: method for treatment of bone marrow in bulk.

T lymphocytes were depleted from donor marrow for 23 patients undergoing allogeneic bone marrow transplantation using an anti-T-cell antibody, CT-2, and complement. The methodology is described in detail for in vitro depletion of large quantities of bone marrow. The extent of T-lymphocyte depletion using various T-cell markers, the percent of marrow lost in the processing and quantity of antibody, and complement needed are presented. These techniques for in vitro T-lymphocyte depletion were reproducible and did result in an average final yield of 47% of the harvested donor marrow.

Antibodies, Monoclonal↗

In vitro analysis of donor bone marrow following monoclonal antibody treatment for the prevention of acute graft versus host disease.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this. CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained. Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III-IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

Acute Disease↗

Depletion of T cells from human bone marrow with monoclonal antibody CT-2 and complement.

CT-2 mouse monoclonal antibody to the E-rosette receptor was used with complement to deplete bone marrow of E-rosette-positive cells (T cells). Depletion of E-rosette-positive cells was complete and nontoxic to hematopoietic progenitor cells. Depletion of E-rosette-positive cells with CT-2 may decrease the severity of graft-versus-host disease following bone marrow transplantation and extend the application of bone marrow transplantation to those without HLA-identical donors.

Antibodies, Monoclonal↗