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R Anderson

Publications and source records attributed to R Anderson.

At least 415 records · Page 23Linked to original sources

Phosphatidylglyceroylalkylamine, a novel phosphoglycolipid precursor in Deinococcus radiodurans.

We report here the structure of a previously uncharacterized phospholipid in the radiation-resistant bacterium Deinococcus radiodurans. This phospholipid, designated lipid 4, was shown by chemical analysis, HF hydrolysis, and nuclear magnetic resonance spectroscopy to be phosphatidylglyceroylalkylamine. Lipid 4 thus contains the unusual lipid constituents glyceric acid and alkylamines, which have previously been identified in two complex phosphoglycolipids from this organism. By [32P]phosphate pulse-chase labeling techniques, lipid 4 was shown to be the precursor of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminylphosphatidylglyceroylalkylamine. While phosphatidylglyceroylalkylamine is rapidly biosynthesized from Pi, its subsequent glycosylation occurs much more slowly. Therefore, we conclude that the final glycosylation step is the rate-limiting event in the biosynthesis of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminyl-phosphatidylglyceroylalkylamine.

Acetates↗

Passive smoking by humans sensitizes circulating neutrophils.

The proinflammatory effects of passive inhalation of cigarette smoke were investigated by exposing a total of 16 healthy, young nonsmokers (mean age 29 +/- 1.4 yr, 11 women and five men) to actively smoking individuals in a poorly-ventilated room. Neutrophil functions were measured before and after 3 h of exposure to cigarette smoke. Passive cigarette smoking was associated with increased leukocyte counts (mean increase 33%, p less than 0.005), chemotaxis (57%, p less than 0.001), and release of reactive oxidants (71%, p less than 0.005) by stimulated neutrophils. These results were confirmed in a second study designed to eliminate the possible complicating effects of serial venepuncture. Plasma concentrations of the proinflammatory cytokines interleukin-1 (IL-1) alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) were not affected by passive smoking. These results indicate that inhalation of sidestream tobacco smoke promotes systemic priming of neutrophils. These potentially proinflammatory events may induce oxidant-mediated tissue damage and carcinogenesis in the lungs of passive smokers.

Adult↗

Epidemiologic patterns of upper respiratory illness and Pneumocystis carinii pneumonia in homosexual men.

The relationship between self-reported upper respiratory illness symptoms (URI) and human immunodeficiency virus Type 1 (HIV-1) was examined in homosexual men using semiannual visits from 1984 to 1988. Temporal and geographic patterns of Pneumocystis carinii pneumonia (PCP) diagnosis in these men during the same time period are also described. URI, including acute sinusitis, was reported more often by 916 HIV-1-seropositive participants than by 2,161 seronegative participants (32.21 versus 28.86% p less than 0.001). For 387 seropositive subjects who progressed to acquired immunodeficiency syndrome (AIDS), the proportion reporting URI peaked one visit pre-AIDS at a level significantly higher than matched control subjects (0.45 versus 0.28, p less than or equal to 0.001). The peak was higher for those with PCP as an initial diagnosis. Reported URI peaked in winter and troughed in summer, and PCP diagnosis rates peaked and troughed 4 months later, respectively. Cities with the highest reported rates of URI also had the highest proportions of AIDS cases with PCP as an initial diagnosis. No temporal or geographic patterns were observed for other HIV-1-related symptoms or non-PCP AIDS diagnoses. These patterns suggest the possibility of a person-to-person transmission of P. carinii similar to that of other respiratory pathogens, which would imply a need to consider stricter methods to prevent nosocomial transmission of this pathogen in inpatient and outpatient settings. Further investigation of these issues is needed.

Acquired Immunodeficiency Syndrome↗

Auranofin inactivates phosphofructokinase in human neutrophils, leading to depletion of intracellular ATP and inhibition of superoxide generation and locomotion.

The effects of the oral gold compound auranofin (AF), at concentrations well within the therapeutic range (0.04-1.5 microM), on human neutrophil functions and energy metabolism were investigated in vitro. At the concentrations tested, this agent had minimal effects on neutrophil degranulation and phagocytosis. However, AF caused dose-related inhibition of neutrophil chemotaxis and stimulus-activated generation of superoxide, which was evident at concentrations as low as 0.04 microM. Inhibition of superoxide generation by activated neutrophils increased with the time of preincubation of the cells with AF at 37 degrees. At low concentrations of AF (less than 0.75 microM), early events (within 5 min) involved in the transduction, assembly, and activity of the neutrophil superoxide-generating enzyme NADPH oxidase appeared to be normal, but the cells were unable to sustain the level of oxygen consumption, superoxide production, and NADPH oxidase activity of the corresponding drug-free control cells. On a mechanistic level, coincubation of neutrophils with AF was associated with decreased glycolytic activity and depletion of intracellular ATP, apparently due to drug-mediated, dose-related inactivation of the glycolytic enzyme phosphofructokinase (PFK). Using purified PFK, the triethylphosphine gold (TEPG) moiety of AF, but not AF per se, caused dose-related inactivation of enzyme activity. These data indicate that the potent inhibition of neutrophil migration and reactive oxidant generation observed during treatment of neutrophils with low, therapeutically attainable concentrations of AF is related to TEPG-mediated inactivation of PFK and consequent interference with cellular energy metabolism and functions.

Adenosine Triphosphate↗

Gas chromatography and mass spectrometry of dimethylethylsilyl ether derivatives of norethisterone metabolites in plasma.

Metabolites isolated from human plasma after oral administration of norethisterone were assayed as their novel dimethylethylsilyl ether derivatives by gas chromatography--mass spectrometry--ion selective monitoring. The major metabolite is 3 alpha, 5 alpha-tetrahydronorethisterone. The unchanged drug is present in a measurable amount even after 8 h of drug administration. The method is accurate, precise and highly sensitive.

Ethers↗

An American clinic for traditional Chinese medicine: comparisons to family medicine and chiropractic.

Patient self-selection delimits the kinds of disorders treated by practitioners of acupuncture and other traditional Chinese modalities in the United States. Based upon a questionnaire administered to 200 first-time patients in a teaching clinic for traditional Chinese medicine (TCM) in California, it was determined that practitioners of TCM attract patients whose health problems would also be appropriate for management by family physicians, chiropractors or mental health professionals. Approximately one-third of presenting complaints can be categorized as presumed organic disorders (many of which may have been medical treatment failures); one-third comprise musculoskeletal problems and headaches; and one-third appear to be psychological or psychosomatic in nature.

Acupuncture Therapy↗

Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis.

We have recently provided evidence that C-reactive protein (CRP) could act as an up-regulatable substrate for membrane-associated neutrophil serine protease(s). The resultant degradation of CRP yielded small soluble bioactive peptides that inhibit many of the proinflammatory functions of activated neutrophils and could oppose the tissue destructive potential of these cells. We report on the reverse phase HPLC separation of the small TCA-soluble peptides obtained when CRP is degraded with nonstimulated or PMA-stimulated neutrophils and purified neutrophil membranes. The amino acid sequence of seven peptides isolated from the CRP digest has been ascertained and synthetic peptides homologous to these sequences have been synthesized. Three of the synthetic peptides corresponding to residues 201-206 (CRP-III), 83-90 (CRP-IV), and 77-82 (CRP-V) of the intact protein were identified to significantly inhibit superoxide production from activated neutrophils at 50 microM whereas CRP-III and CRP-V in addition inhibited neutrophil chemotaxis at this concentration. These peptides act additively and their action likely involves the signal transduction pathways for neutrophil activation.

Amino Acid Sequence↗

On the membrane cytopathology of mouse hepatitis virus infection as probed by a semi-permeable translation-inhibiting drug.

Previous studies of the membrane fusion process have permitted the characterization of membrane permeability changes concomitant with MHV-induced cytopathology. One indication of membrane permeability in MHV-infected cells is their sensitivity to translation inhibition by the normally impermeable amino-glycoside, hygromycin B (Macintyre, G., Wong, F. and Anderson, R. (1989) J. Gen. Virol. 70, 763-768). In the present study, we examine the hygromycin B sensitivity of acutely infected mouse fibroblast L-2 cell and macrophage cultures as well as persistently infected mouse fibroblast LM-K cell cultures. The results suggest that membrane permeability alterations (as indicated by hygromycin B sensitivity) are a common feature of these MHV infections. Hygromycin B "cured" persistently infected LM-K cells as indicated by the absence of detectable virus antigen by immunofluorescence and by the absence of infectious virus even after removal of the drug or co-cultivation with untreated L-2 cells. The results argue against the maintenance of MHV infection by a mechanism involving latently or non-cytolytically infected cells. We conclude therefore that at least one mechanism for MHV persistence depends on virus propagation by cytolytic infection of a small, dynamically changing, fraction of the total cells present in culture.

Animals↗

Mouse fibroblast mutants selected for survival against mouse hepatitis virus infection show increased resistance to infection and virus-induced cell fusion.

We describe here a genetic approach to the analysis of host cell functions involved in determining permissiveness to mouse hepatitis virus (MHV). Using the chemical mutagen, ethyl methane sulfonate (EMS), mouse fibroblast cell mutants were generated which were selected for resistance to cell-killing by MHV. These mutants were then screened for their susceptibility to MHV infection, ability to replicate MHV and relative sensitivity to MHV-induced cell fusion. In contrast to wild type L-2 cells which were acutely and terminally infected by MHV, all five mutants examined replicated MHV in a persistent manner. These mutants showed a reduced susceptibility to MHV infection and an increased resistance to MHV-induced cell fusion. Fusion resistance was specific to that mediated by the MHV E2 protein; mutant as well as wild type L-2 cells were equally sensitive to fusion by polyethylene glycol. The combined effect of reduced infectability and increased fusion resistance was to limit MHV infection to only a small percentage of the total cells in culture, thereby permitting survival of both virus and cells. The observed high rate of generation of the cell mutants suggests that the conversion of a fully MHV-susceptible cell to a semi-resistant one (capable of supporting a persistent infection) is a fairly common event, possibly involving a single mutation.

Animals↗

Inhibition of mitogen-activated proliferation of human lymphocytes by hypochlorous acid in vitro: protection and reversal by ascorbate and cysteine.

Hypochlorous acid (HOCl) at concentrations of 6.25 microM and greater caused statistically significant, dose-related inhibition of mitogen-activated proliferation of human mononuclear leucocytes (MNL). The anti-proliferative effects of HOCl, which were evident using both undepleted and adherent-cell depleted MNL, could not be attributed to decreased mitogen binding by HOCl-treated cells. The anti-oxidants ascorbate and cysteine (50 microM), when added to MNL prior to exposure to HOCl (25 microM), prevented the anti-proliferative effects of the oxidising agent. Likewise reversal of oxidant-mediated inhibition of the responsiveness of MNL to mitogens was observed when ascorbate and cysteine were added after HOCl treatment of the cells. These results suggest that HOCl, derived from activated phagocytes, is a potential mediator of immunosuppression, especially in the setting of abnormal host anti-oxidant defences.

Ascorbic Acid↗

Effects of abrasion therapy on tears in the avascular region of sheep menisci.

This study was designed to test the hypothesis that abrasion of the parameniscal synovium aids healing of a stable tear in the avascular region of the meniscus in a sheep model. In six sheep, a 5-7-mm longitudinal full-thickness tear was made in the avascular inner half of the anterior part of the lateral meniscus. The parameniscal synovium was abraded superiorly and inferiorly from the meniscus periphery to the lesion. Three animals in a control group received identical meniscal tears but no abrasion treatment. A harness prevented weight bearing and maintained the knee fully flexed after surgery. Twelve weeks after the operation, no healing was seen in any tears. Histologic examination revealed in both groups increased numbers of dividing chondrocytes on either side of the tear. In the test group, several layers of fibroblasts, which appeared in two menisci to derive from the upper meniscal surface, were seen covering both cut surfaces of the tear. It is concluded that the distance from the periphery to the defect is too far for abrasion therapy to stimulate sufficient cellular ingrowth to facilitate repair of tears in the avascular region of the meniscus.

Animals↗

Falloposcopy: a microendoscopic technique for visual exploration of the human fallopian tube from the uterotubal ostium to the fimbria using a transvaginal approach.

A transvaginal microendoscopic technique has been developed for safely exploring the human fallopian tube from the utero tubal ostium to the fimbria and adjacent peritoneal cavity. Falloposcopy was performed without complication or evidence of endotubal damage in 44 women, 38 of whom also underwent a concurrent laparoscopy. Eight women with normal tubes served as controls and 36 women with tubal damage underwent falloposcopy in an attempt to document endotubal defects. Previous salpingectomy in 13 women and ostial obstruction in 4 cases left 71 tubes available for falloposcopy. Technical failures, defined as an inability to negotiate the tubal lumen in the absence of obstructive disease occurred in 8 of 71 (11%) procedures. In 63 successful procedures, the tubal lumen was considered to be falloposcopically normal in 28 cases (44%) and contained defects ranging from partial to total obstruction secondary to intraluminal fibrosis within the intramural, isthmic, and ampullary segments in the remaining 35 tubes (56%). Falloposcopy provides a nonincisional modality for defining the normal and abnormal surface anatomy of the tubal epithelium.

Endothelium↗

Chiropractors for and against vaccines.

The publications of philosophically conservative chiropractors document their allegiance to a posture of hostile opposition to health prevention based upon immunization procedures. The challenge to medical anthropology is to make sense of what seems scientifically senseless. This paper attempts to come to an understanding of this position by tracing professional attitudes which are derived from a history of political and economic conflict with the American medical establishment, which emanate from an explanatory model of disease causation that preserves a nineteenth century monocausal theory, and which reflect a process of cultural schizmogenesis. In preserving these heretical medical beliefs, conservative chiropractors, who are trained in the basic medical sciences, defend themselves by basing their opposition to immunization upon imperfections in vaccines that relate to the efficacy, safety and necessity of immunizations. Further, they persist in a belief that chiropractic spinal manipulation provides an alternative method for achieving immune status. This belief has not been subjected to testing in clinical trials or laboratory experiments, and thus becomes a matter of belief rather than of scientific verity. A refusal to advocate or submit to vaccines serves conservative chiropractors as an understandable cultural symbol, but it is a symbol with sinister health costs to those who translate it into non-immune status in a world otherwise still hostage to disease-producing organisms.

Attitude of Health Personnel↗

Proinflammatory interactions of pyocyanin and 1-hydroxyphenazine with human neutrophils in vitro.

The effects of the Pseudomonas aeruginosa-derived pigments, pyocyanin and 1-hydroxyphenazine (1-hp), on membrane-associated oxidative metabolism and release of lysozomal enzymes by human neutrophils were investigated in vitro. Pyocyanin, but not 1-hp, increased the generation of superoxide and the rate and duration of oxygen uptake by activated neutrophils. Both agents increased the myeloperoxidase-mediated iodinating activity of neutrophils, which in the case of 1-hp was due to stimulation of the release of myeloperoxidase by activated neutrophils. 1-hp also increased the release of lysozyme by activated neutrophils. Pyocyanin caused only slight enhancement of the release of myeloperoxidase and lysozyme by stimulated neutrophils but was more potent with respect to the release of the specific granule marker, vitamin B12-binding protein. These data indicate the existence of diverse, proinflammatory interactions of pyocyanin and 1-hp with human phagocytes, which may intensify neutrophil-mediated tissue damage during P. aeruginosa infections.

Cell Degranulation↗