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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 217 records · Page 12Linked to original sources
PubMed1997

Roxithromycin, clarithromycin, and azithromycin attenuate the injurious effects of bioactive phospholipids on human respiratory epithelium in vitro.

The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD). All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations > or = 1 microgram/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes. When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD. These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants. Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.

Anti-Bacterial Agents↗
PubMed1997

Calcium efflux and influx in f-met-leu-phe (fMLP)-activated human neutrophils are chronologically distinct events.

The kinetics of efflux of calcium mobilized from intracellular stores following activation of human neutrophils with the synthetic chemotactic tripeptide, fMLP (1 microM), as well as that of the subsequent store-operated influx of this cation, has been measured by radiometric procedures using 45Ca. These procedures enabled distinction between net efflux and influx of 45Ca. Preincubation of neutrophils in medium containing 45Ca as the sole source of Ca2+, followed by activation with fMLP, resulted in a rapid efflux of the cation, which coincided with its release from intracellular stores. Efflux terminated at approximately 30 s after addition of fMLP to neutrophils and resulted in the loss of 42 +/- 3% (P < 0.005) of cell-associated 45Ca. Net influx of 45Ca, which was insensitive to the voltage-dependent Ca2+ channel blockading agent, verapamil (20 microM), could only be detected at 30-60 s after the addition of fMLP to neutrophils, and proceeded for about 5 min, resulting in intracellular concentrations of Ca2+ which were 27 +/- 3% (P<0.05) higher than preactivation levels. These results demonstrate that the efflux of cytoplasmic Ca2+ mobilized from intracellular stores during activation of neutrophils by fMLP, and the subsequent influx of extracellular Ca2+ to replete these stores, are chronologically distinct events in fMLP-activated neutrophils.

Calcium↗
PubMed1997

p53: functions, mutations and sarcomas.

The p53 gene is the most commonly altered gene in a multitude of human cancers. The alterations can be acquired somatically or transmitted through the germ-line. Bone and soft tissue sarcomas are frequently found to have acquired abnormalities in the p53 and mdm-2 genes. In soft tissue sarcoma, the amplification of the mdm-2 gene and the binding of its oncogene product to wild-type p53 protein functionally inactivates normal p53-regulated growth. Inherited mutations of the p53 gene are associated with the rare Li-Fraumeni familial cancer syndrome. Various tumor types arise in these families, with sarcomas of the bone and soft tissues and carcinoma of the breast being the most frequently observed. Transgenic mice with highly expressed mutated p53 have a higher incidence of tumors, including predominantly osteosarcomas and soft tissue sarcomas. In close similarity with the Li-Fraumeni syndrome, homozygously p53-null mice (transgenic mice carrying two non-functional p53 allele) are developmentally normal however they are susceptible to spontaneous tumor formation. This article reviews briefly the structure, function, and dysfunction of the p53 tumor-suppressor gene with particular focus on its role in the development of bone and soft tissue sarcoma.

Animals↗
PubMed1997

Novel tetramethylpiperidine-substituted phenazines are potent inhibitors of P-glycoprotein activity in a multidrug resistant cancer cell line.

The multidrug resistance (MDR)-neutralizing and cytotoxic properties of 16 novel tetramethylpiperidine (TMP)-substituted phenazines were compared with those of clofazimine and B669 using a P-glycoprotein (P-gp)-expressing undifferentiated, human leukemia cell line (K562/MMB). Unchlorinated TMP-substituted phenazine molecules were more cytotoxic than their chlorinated counterparts, while the halogenated molecules, especially those with chlorine atoms at position 3 on the aniline and phenyl rings, were less cytotoxic but more effective as chemosensitizing, P-gp-neutralizing agents. One of the TMP-substituted phenazines, B4121, increased the sensitivity of K562/MMB cells to vinblastine by 100-fold. TMP-substituted phenazines are a novel class of pharmacologic anti-cancer agents with both direct cytotoxic, as well as MDR-neutralizing anti-tumor properties.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

My labyrinth.

Each of us is taking a professional journey. We use our scholarship and our relationship building skills to learn and mentor, experience and contribute, and lead and follow. Our creativity, flexibility, and adaptability provide us with a "centering" that enhances our success, but our only reason to pursue the journey with vigor is to create a better environment for professionals to practice and for patients to receive care. Let us know ourselves so we can ground the journey with integrity.

Humans↗
PubMed1997

Managed care: increased opportunities for acute-care nurse practitioners.

Significant changes in the health-care delivery system during the past few years has resulted in shifts in managed care. Under this system, the fundamental assumptions of health-care delivery have been challenged and are beginning to change: emphasis on health, not illness, primary versus specialty care, hospital-based care to care networks, and revision of medical education patterns. The resulting opportunity for nursing has assisted in the expansion of its care to a practitioner model within the acute-care setting. Through case management and direct acute-care patient management, acute-care nurse practitioners (ACNPs) may ultimately contribute to reductions in hospitalization costs. Literature suggesting actual costs of ACNPs to be high must be measured against their invaluable contributions to increased quality of care. Detailed evaluation programs are needed for more complete analysis. An example of ACNP practice at a large teaching hospital shows varied interpretations of the role.

Hospitals, Teaching↗
PubMed1997

Acetabular labrum tear in a 15-year-old male: diagnosis with correlative imaging.

A 15-year-old male with unresolved hip pain after minor trauma is presented. The diagnosis of an acetabular labral tear was made using correlative scintigraphic and magnetic resonance (MR) imaging, obviating the more invasive investigations of arthrography or arthroscopy of the hip. The clinical and radiological features of this lesion are reviewed. Undiagnosed, acetabular labral tears may result in considerable morbidity. Appropriate operative or conservative management of the condition usually provides symptomatic relief.

Accidental Falls↗
PubMed1997

Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes.

Although endothelial cells have been speculated to be a target in the pathogenesis of dengue hemorrhagic fever (DHF), there has been little evidence linking dengue virus infection to any alteration in endothelial cell function. In this study, we show that human umbilical vein endothelial cells become activated when exposed to culture fluids from dengue virus-infected peripheral blood monocytes. Maximum activation was achieved with culture fluids from monocytes in which virus infection was enhanced by the addition of dengue virus-immune serum, thus correlating with epidemiological evidence that prior immunity to dengue virus is a major risk factor for DHF. Activation was strongest for endothelial cell expression of VCAM-1 and ICAM-1. In contrast, activation of endothelial cell E-selectin expression appeared to be more transient, as indicated by its detection at 3 h, but not at 16 h, of treatment. Treatment of monocyte culture fluids with anti-tumor necrosis factor alpha (TNF-alpha) antibody largely abolished the activation effect (as measured by endothelial cell expression of ICAM-1), whereas treatment with IL-1beta receptor antagonist had a much smaller inhibitory effect on activation. Endothelial cells inoculated directly with dengue virus or with virus-antibody combinations were poorly infectable (compared to Vero cells or peripheral blood monocytes), and virus-inoculated endothelial cells showed no increased expression of VCAM-1, ICAM-1, or E-selectin. Taken together, the results strongly indicate that dengue virus can modulate endothelial cell function by an indirect route, in which a key intermediary is TNF-alpha released from virus-infected monocytes.

Adult↗
PubMed1997

Evaluation of social status as a contributing factor to the stroke belt region of the United States.

BACKGROUND AND PURPOSE: The southeastern United States has stroke mortality rates above the national average. The causes for this excess mortality are unknown; however, lower socioeconomic status (SES) is a risk factor for stroke, and the lower SES in the Southeast is a potential cause. In this report we assess the proportion of the excess stroke mortality attributable to SES. METHODS: The more than 400,000 participants in the National Longitudinal Mortality Study were categorized into three regions: the coastal plain region of North Carolina, South Carolina, and Georgia ("stroke buckle"); the remainder of these states plus five other southern states ("stroke belt"); and the remainder of the United States. The stroke mortality rates were calculated with and without adjustment for SES, and the proportion of the excess mortality attributable to SES was estimated. RESULTS: In persons between the ages of 35 and 54 years, stroke mortality in the stroke buckle is estimated to be more than twice that of the rest of the nation and 1.7 times greater for ages 55 to 74 years. For persons in the stroke belt, the stroke mortality was 1.3 times greater than that in the rest of the nation for the ages of 35 to 54 and 55 to 74 years. Less than 16% of this excess stroke morality was attributable to SES. CONCLUSIONS: SES does not appear to be a major contributor to the excess mortality in the southeastern United States. Of additional concern is the stroke buckle region, which was shown to have stroke mortality rates substantially greater than those in the traditionally recognized stroke belt.

Adult↗
PubMed1997

Impact of patch testing on dermatology-specific quality of life in patients with allergic contact dermatitis.

BACKGROUND: A dermatology-specific quality-of-life instrument has been created and validated for its sensitivity, reproducibility, content, and construct validity. This instrument was used in an observational prospective study that evaluated the cost-effectiveness of patch testing in patients with contact dermatitis and suspicion of allergic component. OBJECTIVE: This multicenter, prospective, observational study was designed to study the various direct and indirect costs associated with diagnosis and treatment of suspected allergic contact dermatitis and the benefits of diagnosis with and without patch testing. The costs and benefits of various methods of diagnosis are evaluated to determine if patch testing is more cost-effective as a diagnostic method. One of the outcomes evaluated was the quality of life of the participants in the study and the impact of patch testing on this cohort. METHODS: A total of 567 subjects were enrolled to obtain evaluable data from at least 500 subjects from ten study centers; the investigators were chosen so as to obtain a mix of stratified degrees of usage of patch testing. Data were collected on demographics, physical characteristics, history of disease, visits to physicians, and, to evaluate costs, the use of resources such as drugs, nondrug substances, and services; other outcome data collected were on physician evaluation of improvement, confirmation of diagnosis, physician opinion of the disease management, and patient evaluation of dermatology-specific quality of life (DSQL), and pertinent economic factors. Only 6-month and 12-month follow-up visits were mandatorily scheduled according to the protocol; however, participants and providers were free to arrange additional visits as deemed necessary for health care. RESULTS: This report focuses on the evaluations at the 6-month follow-up. There are completely evaluable data on pharmacoeconomics and DSQL for 431 patients. About 43% were patch tested, and the rest were diagnosed using the information from history and physical examinations. There was significantly better improvement in each of the DSQL domains in patch tested subjects compared with non-patch-tested subjects. In addition, patients treated in "low" use clinics had lower quality of life at 6-month follow-up than those treated in "high" use clinics. CONCLUSION: Patch testing helps to diagnose the etiology of contact dermatitis early and treat the disease before it becomes chronic, thus reducing resources used and improving patient quality of life considerably.

Case-Control Studies↗
PubMed1996

Leg proprioceptors of the tobacco hornworm, Manduca sexta: organization of central projections at larval and adult stages.

Organization of the central neuropil of the insect ganglion is characterized in part by a modality-specific layering of afferent projections. This organization has been particularly well described for the central projections of thoracic leg sensory neurons of adult locusts, crickets, and flies. Tactile sensory neurons project into a ventral layer of neuropil, while proprioceptive sensory neurons project into an intermediate layer of neuropil. In order to determine whether a modality-specific layering exists in the CNS of larval Manduca sexta, we have examined the projections of sensory neurons innervating one class of putative proprioceptors, the campaniform sensilla, of the larval metathoracic legs. We find that campaniform sensory neurons of the larval legs have central projection patterns that generally distinguish them from each other and from the tactile sensory neurons. The campaniform projections, however, are not completely segregated from tactile projections in ventral layers of neuropil, as has been described in other insects. By contrast, the projections of campaniform sensory neurons from the adult legs are more extensive and elaborate than their larval counterparts and dramatically different from projections of nearby adult tactile hairs, having extensive arborizations in more dorsal regions of neuropil while those of tactile sensory neurons are restricted to very ventral layers of neuropil. This difference in organization of the afferent projections in larval and adult ganglia may reflect different functions of the leg sensilla and different functions of the legs at the two stages.

Animals↗
PubMed1996

Membrane stabilizing, anti-oxidative interactions of propranolol and dexpropranolol with neutrophils.

We have investigated the effects of the beta-adrenoreceptor-blocking agent, propranolol (9-300 microM) on several pro-inflammatory activities of human neutrophils in vitro. Superoxide production by calcium ionophore (A23187)-activated neutrophils was particularly sensitive to inhibition by low concentrations (9-18.7 microM) of this drug. However, inhibition of superoxide generation by neutrophils activated with phorbol myristate acetate (PMA), opsonized zymosan (OZ), and arachidonate (AA) only occurred with higher concentrations of propranolol, and coincided with decreased intracellular calcium fluxes, phospholipase A2 (PLA2) activity and synthesis of platelet-activating factor (PAF). Propranolol possessed neither cytotoxic nor superoxide-scavenging properties but, using a haemolytic assay of membrane-stabilizing activity, this agent neutralized the membrane-disruptive effects of the bioactive phospholipids, lysophosphatidylcholine (LPC), PAF, and lysoPAF(LPAF). A mechanistic relationship between the anti-oxidative and membrane-stabilizing properties of propranolol was suggested by the observation that pretreatment of neutrophils with LPC or PAF eliminated the inhibitory effects of the drug on superoxide generation by PMA-activated neutrophils. Dexpropranolol, a stereoisomer with minimal beta-blocking activity, and propranolol were equally effective with respect to their membrane-stabilizing and anti-oxidative interactions with neutrophils, but several other beta-blocking agents (atenolol, metoprolol, sotalol, and timolol) did not possess these activities. Inhibition of oxidant generation is, therefore, not a common property of beta-blocking agents and, in the case of propranolol, appears to occur as a consequence of membrane-stabilization rather than by beta-receptor-directed effects.

Acridines↗
PubMed1996

FGF-2 influences cell movements and gene expression during limb development.

FGF-2 is proposed to be an important ectodermal signal directing limb outgrowth and patterning. Consistent with this hypothesis we show that ectopic application of FGF-2 can maintain the apical ectodermal ridge (AER)-dependent expression of Sonic hedgehog (Shh), and AER-dependent zone of polarizing activity (ZPA) signaling. We also find that ectopic FGF-2 applied to the posterior wing bud caused a dramatic change in the morphology of the limb bud, and results in limbs that display a reduction in the length of individual skeletal elements and loss of digits. Associated with these morphological changes was an FGF-2-stimulated expansion and bifurcation of the expression domains of two posteriorly expressed genes, Shh and HoxD13. Applying FGF-2 at a central or anterior location in the limb bud did not alter the Shh expression domain or cause digit loss. To test whether ectopic application of FGF-2 into the posterior limb bud was influencing the movement of limb bud cells, we used the lipophilic dye DiI to map the behavior of posterior cells in response to FGF-2. In response to FGF-2 posterior limb bud cells move in both a proximal and a distal direction, causing the initially labeled cell population to bifurcate into two distinct domains. Our data suggest that FGF-2 is influencing limb outgrowth by modifying cell movements and subsequent position-specific cell-cell interactions that are important for limb morphogenesis.

Animals↗