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Biomedical subjects

W Johnson

Publications and source records attributed to W Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1992

Adherence of Legionella pneumophila to guinea pig peritoneal macrophages, J774 mouse macrophages, and undifferentiated U937 human monocytes: role of Fc and complement receptors.

Legionella pneumophila, the causative agent of Legionnaires' disease, is a facultative intracellular pathogen of alveolar macrophages. Although previous studies have demonstrated that specific antibody facilitates uptake of L. pneumophila by phagocytic cells, the role of complement has been unclear. Thus, we have examined the relative contributions of Fc gamma- and complement receptor-mediated adherence to guinea pig peritoneal macrophages, U937 human monocytic cells, and J774 mouse macrophage cells. Opsonization of L. pneumophila (Philadelphia 2) with polyclonal immunoglobulin G promoted maximum adherence to guinea pig macrophages. In contrast, incubation in the presence of 20% fresh nonimmune human serum from a single donor did not promote adherence. The results obtained with U937 and J774 cells paralleled those obtained with guinea pig macrophages. In the absence of specific antibody, opsonization with guinea pig complement did not enhance adherence of the Philadelphia 1, Philadelphia 2, or Knoxville strain. However, when complement was added to heat-inactivated, specific antiserum, a fourfold increase in the number of adherent organisms was observed. Blocking studies utilizing membrane receptor-specific monoclonal antibodies demonstrated that both Fc and complement receptors mediated adherence of organisms treated with complement in the presence of specific antibody. These results suggest that complement augments adherence of L. pneumophila only when acting in concert with specific antibody.

Animals↗
PubMed1992

Legionella pneumophila lipopolysaccharide activates the classical complement pathway.

Legionella pneumophila is a gram-negative bacterium capable of entering and growing in alveolar macrophages and monocytes. Complement and complement receptors are important in the uptake of L. pneumophila by human mononuclear phagocytes. The surface molecules of L. pneumophila that activate the complement system are unknown. To identify these factors, we investigated the effects of L. pneumophila lipopolysaccharide (LPS) on the classical and alternative complement pathways of normal human serum by functional hemolytic assays. Although incubation of LPS in normal human serum at 37 degrees C resulted in the activation of both pathways, complement activation proceeded primarily through the classical pathway. Activation of the classical pathway by LPS was dependent on natural antibodies of the immunoglobulin M class that were present in various quantities in sera from different normal individuals but were absent in an immunoglobulin-deficient serum obtained from an agammaglobulinemic patient. Additional studies using sheep erythrocytes coated with LPS suggested that the antibodies recognized antigenic sites in the carbohydrate portion of LPS. The ability of LPS to interact with the complement system suggests a role for LPS in the uptake of L. pneumophila by mononuclear phagocytes.

Complement C1↗
PubMed1992

Treatment of occult or late overt testicular relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) designed a randomized two-arm protocol (8304) to improve the survival of children with acute lymphoblastic leukemia (ALL) who experience an isolated testicular relapse and to evaluate the efficacy of teniposide (VM-26) and doxorubicin as intensification agents during second remission. The outcome and toxicity observed in 80 patients with isolated testicular leukemia treated on POG 8304 are presented. PATIENTS AND METHODS: The following are common features of POG 8304: (1) remission reinduction therapy with vincristine, prednisone, and doxorubicin; (2) bilateral testicular irradiation (2,600 cGy) during reinduction therapy; (3) CNS prophylaxis with intrathecal hydrocortisone, methotrexate (MTX), and cytarabine (Ara-C); and (4) continuation therapy (for 80 weeks) with alternating 6-week cycles of oral mercaptopurine (6-MP)/MTX and intravenous vincristine and cyclophosphamide. Treatment differences consisted of pulses (administered every 7 weeks) of either prednisone and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2) during continuation therapy and a 4-week late intensification phase with either vincristine, prednisone, and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2). RESULTS: Fifty-five boys with ALL had isolated microscopic testicular leukemia detected by an elective biopsy at completion of initial treatment, and 25 had a late (greater than or equal to 6 months off-therapy) isolated overt testicular relapse. All patients with overt testicular leukemia attained a second clinical remission, and no patient with microscopic testicular leukemia progressed during reinduction. Of 42 patients on arm 1, 11 have relapsed compared with 18 of 38 patients on arm 2 (log-rank analysis, P = .22), indicating no significant difference between an anthracycline and an epipodophyllotoxin-Ara-C combination in the treatment of testicular leukemia. The overall 4-year event-free survival (EFS) among boys with occult testicular relapse was 53% +/- 8%. Age greater than 10 years at initial diagnosis, a WBC count greater than 50,000/microL at diagnosis, and black race were associated with a worse outcome. The 4-year EFS for boys with a late overt testicular relapse was 84% +/- 10%, and these patients fared significantly better than patients with occult disease (P = .007). CONCLUSION: The treatment approach reported here can secure a prolonged second remission in many patients with occult or late overt testicular leukemia.

Adolescent↗
PubMed1992

Optimal administration of dual screening tests for detecting a characteristic with special reference to low prevalence diseases.

We consider the problem of deciding optimally whether a characteristic exists based on one or two screening tests. We discuss the relative merits of giving either one or two tests, including the order in which they might be given, as well as their costs. Operating in the Bayesian mode, we derive posterior distributions for the accuracies of the tests and the prevalence of the characteristic. Applications to detecting rare conditions, such as the AIDS virus, are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Testing Hardy-Weinberg equilibrium on allelic data from VNTR loci.

Several methods for testing independence of pairs of alleles in a population that are obtained from a VNTR locus are presented. We assume an exchangeable quasi-continuous distribution of the fragment lengths used to measure the allelic pairs. Bivariate-estimated quantiles computed from the quantiles of the entire data set are then utilized for testing independence. These methods have the advantage of being minimally susceptible to the criticism of (a) the inability of a technology to measure a few small-sized or rather large-sized fragments and (b) inadequate estimation of the homozygotic proportion.

Alleles↗
PubMed1992

Methodology for in-process determination of residual water in freeze-dried products.

The integrity of freeze-dried biological products after reconstitution, as well as their stability during storage, is often more sensitive to small variations in residual moisture level than traditional low molecular weight drugs. Susceptibility to over-drying has also been documented for biological products. This places additional demands on the quality of in-process monitoring to achieve the desired level of residual water. This discussion is a critical overview of methodology for in-process moisture determination, including product temperature measurement, comparative pressure measurement, pressure rise, and residual gas analysis. Advantages and limitations of these methods are discussed.

Biological Products↗
PubMed1991

Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study.

Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure.

Adolescent↗
PubMed1991

Chronic use of the calcium channel blocker nifedipine has no significant effect on bone metabolism in men.

Calcium channel blockers have been reported to have such diverse effects on reduction in protein synthesis, diminished incorporation of proline into new collagen, and decreased hormone release in vitro. The chronic affect of the calcium channel blocker nifedipine was examined in vivo to determine the possible impact of pharmacologic calcium channel blockade on bone metabolism. Eleven Caucasian males treated with an average of 40 mg/d nifedipine for an average of three years were compared to 11 control males matched for age, height, weight, activity level, cardiovascular status, and calcium intake. No significant differences between groups were noted in bone mineral density at the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle and trochanter), and proximal and distal radius. There were also no significant differences in parameters of bone turnover (alkaline phosphatase, osteocalcin, urine calcium/creatinine, and hydroxyproline/creatinine ratio), or hormones that might affect calcium metabolism and bone (testosterone, PTH, 25(OH) vitamin D, and calcitonin). In summary, chronic nifedipine use in males is not associated with either a beneficial or adverse effect on bone metabolism.

Adult↗
PubMed1991

Acquisition of iron by Legionella pneumophila: role of iron reductase.

Legionella pneumophila has been shown to survive and multiply in a variety of intracellular environments, including protozoa and human mononuclear phagocytes. However, the mechanism by which this organism acquires iron in the intracellular environment has not been studied. Since L. pneumophila does not produce siderophores, alternative methods of iron acquisition were investigated. Virulent strains of L. pneumophila were able to grow in media containing as little as 3 microM iron, whereas avirulent cells required a minimum of 13 microM iron for growth. Neither virulent nor avirulent cells were able to utilize 55Fe bound to transferrin. When incubated in the presence of 55Fe in the form of ferric chloride, both virulent and avirulent cells accumulated equal amounts of iron. The uptake of iron was energy dependent as indicated by inhibition of 55Fe uptake at 4 degrees C and preincubation of the cells with KCN. Treatment of virulent cells with pronase or trypsin had no effect on iron uptake. In contrast, pronase or trypsin treatment of avirulent cells resulted in increased uptake of iron. Iron reductase activity in both virulent and avirulent cells was demonstrated, with the highest specific activity associated with the periplasmic fraction. Maximum reductase activity of virulent cells occurred with NADH as the reductant. In contrast, avirulent cells showed a twofold increase in enzyme activity when NADPH was used as the reductant. These results suggest that an iron reductase is important in iron acquisition by L. pneumophila.

Biological Transport↗
PubMed1991

Pitted red cell counts in Nigerian children with sickle cell anemia: correlation with age and splenic size.

Using direct interference phase-contrast microscopy (Normansky Optics), pit counts were performed on 32 HbSS patients, aged 3 to 17 years. The influence of age and splenic size on counts were also investigated. Nine HbSS and 15 HbAA age and sex-matched, healthy individuals served as controls. The mean +/- SD counts in the three groups were 11.1 +/- 9.1%, 1.7 +/- 1.4% and 1.8 +/- 1.7%, respectively. The older SS patients tended to have higher values, but the linear correlation with age was not impressive (r = 0.28). Seventeen (53.1%) patients had counts greater than 10%, while 8 (25%) had less than 3.5%. Five patients with gross splenomegaly had a mean count of 4.3 +/- 1.9%, significantly lower than the figure of 12.3 +/- 7.9% for the patients without splenomegaly (P less than .001), demonstrating retained reticulo-endothelial function in such patients.

Adolescent↗
PubMed1990

Usefulness of angioplasty during acute myocardial infarction in patients with prior coronary artery bypass grafting.

The efficacy and risk of reperfusion strategies for myocardial infarction in patients with prior coronary artery bypass surgery are uncertain. In this study 72 patients with prior bypass grafting underwent direct percutaneous transluminal coronary angioplasty without antecedent thrombolytic therapy. There were 26 anterior and 46 inferior infarctions, including 11 patients (15%) in cardiogenic shock. The baseline ejection fraction was less than 40% in 47 (65%) patients. Angioplasty was successful in 41 of 48 (85%) vein grafts and 24 of 24 (100%) arteries (difference not significant) at 5.1 +/- 4.0 hours from the onset of symptoms (79% treated less than 6 hours). There were no urgent bypass operations, strokes or transfusions. In-hospital survival was 90% (nonshock 95% vs shock 64%, p less than 0.01). Symptomatic acute reclosure occurred in 1 patient. Predischarge coronary arteriography in 34 patients demonstrated continued vessel patency in 32 infarct vessels (94%), although 5 of these vessels were redilated for restenoses. Predischarge paired ventriculography in 26 patients showed an increase in ejection fraction from 44 +/- 16% to 51 +/- 18% (p less than 0.01). One- and 3-year actuarial survival was 89 and 87%. Thus, prior coronary surgery should not preclude reperfusion therapy by direct angioplasty, which can be accomplished with low procedural risk, improvements in ventricular function and excellent in-hospital and late survival.

Aged↗
PubMed1990

Analysis of proteins and glycoproteins at the picomole level by on-line coupling of microbore high-performance liquid chromatography with flow fast atom bombardment and electrospray mass spectrometry: a comparative evaluation.

A comparison of continuous-flow fast atom bombardment (FAB) mass spectrometry and nebulization-assisted electrospray for analysis of proteins and glycoproteins by high-performance liquid chromatography (HPLC)/mass spectrometry is presented. The evaluation was made using enzymatic digests of recombinant soluble CD4 glycoprotein and recombinant hepatitis B surface antigen and a mixture of HPLC retention standard peptides. These samples were analyzed by reversed-phase HPLC on a microbore (1 x 100 mm C18) gradient HPLC system with 10% or 20% of the eluent containing approximately 20-100 pmol of the sample directed into the continuous-flow FAB mass spectrometric or electrospray mass spectrometric source, respectively. The techniques were evaluated on the criteria of chromatographic integrity, ease of data analysis, protein sequence coverage, discrimination effects, ability to detect glycopeptides, simplicity of operation, and sensitivity. Both techniques produce useful peptide molecular weight data from comparable amounts of sample injected. However, the nebulization-assisted electrospray system is capable of yielding higher peptide mapping coverages with the least sample consumed in toto due in part to the wider mass ranges resulting from the multicharging effect and to the ability to detect glycopeptides. Under the experimental conditions employed here no fragmentation was observed in the electrospray mass spectra. In contrast, significant, sequence informative fragmentation was occasionally observed for peptides in the continuous-flow FAB mass spectral data.

Amino Acid Sequence↗
PubMed1990

PTCA of the left coronary artery when the right coronary artery is chronically occluded.

Angioplasty of the left coronary artery was undertaken in 65 patients with a chronic total occlusion of the right coronary artery (CLOSED RCA) and in 105 patients with no significant disease in the right coronary artery (OPEN RCA). No patient had attempted dilatation of the right coronary artery. CLOSED RCA versus OPEN RCA patients differed with respect to presence of poor left ventricular (LV) function (12% versus 4%, p = 0.07), number of stenoses per patient (2.2 versus 1.8, p less than 0.05), and stenoses in both left anterior descending and left circumflex artery (39% versus 23%, p less than 0.05). Procedural complications were low for both CLOSED RCA (one death) and OPEN RCA (one emergency bypass surgery) patients. At late follow-up (mean = 17 months), there was no difference in survival between CLOSED RCA and OPEN RCA patients (95% versus 93%, p = NS). Late cardiac events (death, bypass surgery, or myocardial infarction) occurred in 26% of CLOSED RCA patients and in 16% of OPEN RCA patients (p = ns). The absence of angina at follow-up was more frequent in OPEN RCA compared with CLOSED RCA patients (84% versus 61%, p less than 0.01). Angioplasty of the left coronary artery can be performed in CLOSED RCA patients without excessive procedural risk; however, at follow-up continued anginal symptoms are common.

Angioplasty, Balloon, Coronary↗
PubMed1990

Lung edema caused by high peak inspiratory pressures in dogs. Role of increased microvascular filtration pressure and permeability.

Mechanical ventilation with high peak airway pressures (Paw) has been shown to induce pulmonary edema in animal experiments, but the relative contributions of transvascular filtration pressure and microvascular permeability are unclear. Therefore, we examined the effects of positive-pressure ventilation on two groups of open-chest dogs ventilated for 30 min with a peak Paw of 21.8 +/- 2.3 cm H2O (Low Paw) or 64.3 +/- 3.5 cm H2O (High Paw). No hemodynamic changes were observed in the Low Paw group during ventilation, but mean pulmonary artery pressure (Ppa) increased by 9.9 cm H2O, peak inspiratory Ppa by 24.6 cm H2O, and estimated mean microvascular pressure by 12.5 cm H2O during High Paw ventilation. During the same period, lung lymph flow increased by 435% in the High Paw and 35% in the Low Paw groups, and the terminal extravascular lung water/blood-free dry weight ratios were 5.65 +/- 0.27 and 4.43 +/- 0.13 g/g, respectively, for the two groups. Lung lymph protein clearances and minimal lymph/plasma ratios of total protein were significantly higher (p less than 0.05) after 2 h of increased left atrial pressure (PLA) in the High Paw group versus the Low Paw group, which indicates a significant increase in microvascular permeability. Lymph prostacyclin concentration in pulmonary lymph, measured as the stable metabolite 6-0-PGF1 alpha, was increased significantly by 70 to 150% from baseline (p less than 0.05) in both groups during the periods of increased Paw and increased PLA, but it was not significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Coronary bifurcation stenoses: the kissing balloon Probe technique via a single guiding catheter.

A new technique employing two balloon probes via a single (large-lumen) guiding catheter is described. Examples involving the left anterior descending, diagonal, left main (protected), left circumflex-obtuse marginal, and atrioventricular branches and the right coronary artery-posterior descending and posterolateral branches are described and illustrated. This new technology (balloon probes and large-lumen guiding catheter) permits an effective and simplified alternative to the use of the single-guide/two-wire and double-guide/two-dilatation catheter-wire approaches in selected cases in which significant branch vessels (vis-a-vis myocardial regional blood supply) are at risk.

Aged↗
PubMed1989

Correlation artifacts in speed of sound estimation in scattering media.

A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the second order statistical properties of the stairstep artifact are derived.

Computer Simulation↗
PubMed1989

Characterization of the selective inhibition of growth of virulent Legionella pneumophila by supplemented Mueller-Hinton medium.

The phenotypic difference between virulent and avirulent Legionella pneumophila with regard to growth on supplemented Mueller-Hinton (SMH) agar was investigated. Defined populations of virulent and avirulent L. pneumophila were inoculated onto hybrid growth media containing the combination of SMH agar components with potassium phosphate-buffered charcoal-yeast extract agar. The casein acid hydrolysate component of SMH agar was found to be inhibitory to the growth of virulent but not avirulent cells. The selectively inhibitory component of the casein acid hydrolysate was identified as NaCl.

Agar↗