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result(s) for
"Lefkowitz, Doris"
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Macrophage–neutrophil interaction: A paradigm for chronic inflammation revisited
by
Lefkowitz, Stanley S
,
Lefkowitz, Doris L
in
Arthritis, Rheumatoid - etiology
,
Arthritis, Rheumatoid - immunology
,
Arthritis, Rheumatoid - physiopathology
2001
Macrophages have been described as ‘factories’ of pro‐inflammatory cytokines. Several years ago the present investigators reported that binding of inactive myeloperoxidase (iMPO) to the macrophage‐mannose receptor resulted in the induction of TNF and other cytokines. Also, if endothelial cells were incubated with iMPO, but not enzymatically active myeloperoxidase (MPO), upregulation of cytokine mRNA and cytokines was observed. Taken in their entirety, the data suggest a dichotomy of function for myeloperoxidase; that is, enzymatically active MPO functions primarily in cell killing through the ‘cytotoxic triad’ and iMPO functions as an immunoregulatory molecule through the induction of numerous cytokines. These studies underscore a previously unrecognized interaction among neutrophils, endothelial cells and macrophages, resulting in the induction of TNF and perpetuation of inflammation. The inflammation induced could be relevant in a number of diseases in which neutrophils play a prominent role. The importance of this interaction in the pathogenesis of rheumatoid arthritis is currently under investigation.
Journal Article
Alveolar Macrophage Activation by Myeloperoxidase . A Model for Exacerbation of Lung Inflammation
by
Lefkowitz, Stanley S
,
Stuart, Rodney
,
Bollen, Alex
in
Animals
,
Cytokines - genetics
,
Enzyme-Linked Immunosorbent Assay
2002
Inflammation of the lung is characterized by the influx of increased numbers of various leukocytes including polymorphonuclear leukocyte (PMN) neutrophils. In addition to cells, numerous studies have pointed to the role of tumor necrosis factor-alpha in the inflammatory process. This study addresses a previously unrecognized interaction between neutrophil-derived myeloperoxidase (MPO) and resident alveolar macrophages (AMø). Rat AMø exposed to either enzymatically active recombinant MPO or enzymatically inactive MPO (iMPO) exhibited an increased respiratory burst (RB). When iMPO was employed, the enhancement of the RB was greater than that observed with MPO. Although the RB was greater with iMPO, macrophage (Mø)-mediated intracellular candidic activity was equivalent for both MPO and iMPO. It is known that pro- inflammatory cytokines contribute to the inflammatory process. When rat AMø were exposed to both forms of myeloperoxidase, iMPO demonstrated greater upregulation of cytokine genes as well as product. These data suggest that at the site of inflammation, neutrophil-derived MPO and iMPO stimulate AMø, resulting in an increased inflammatory and cytotoxic state, and thereby contributing to the general lung inflammatory response.
Journal Article
Phagocytosis and Intracellular Killing of Candida albicans by Macrophages Exposed to Myeloperoxidase
by
Moguilevsky, Nicole
,
Lefkowitz, Doris L.
,
Lefkowitz, Stanley S.
in
Adjuvants, Immunologic - pharmacology
,
Animals
,
Biological and medical sciences
1996
Candida albicans is an opportunistic pathogen whose resurgence coincides with the rising number of AIDS patients. Neutrophils are known to be involved in the clearance of Candida infections; however, the role of macrophages in host defenses against this organism is not well understood. The present study was undertaken to examine an unrecognized interaction between neutrophils and macrophages resulting in enhanced killing of candidae in vitro. Murine peritoneal macrophages exposed to recombinant myeloperoxidase exhibited enhancement of the respiratory burst, increased phagocytosis, and a dose-dependent increase in intracellular killing of Candida species. Radical scavengers reduced the killing, indicating a role of reactive oxygen intermediates in the candidacidal activity observed. These data suggest that at the site of infection, myeloperoxidase released from neutrophils activates macrophages and induces microbicidal activity.
Journal Article
The Medical Expenditure Panel Survey: A National Health Information Resource
by
Cohen, Steven B.
,
Taylor, Amy K.
,
Potter, D.E.B.
in
Data collection
,
Data Collection - methods
,
Data Collection - statistics & numerical data
1996
This article describes the Medical Expenditure Panel Survey (MEPS), the third in a series of nationally representative surveys of medical care use and expenditures sponsored by the Agency for Health Care Policy and Research. The MEPS is designed to provide extensive data on the types of health care services American use, how frequently they use them, how much is paid for the services, and who pays for them. It also will provide information on the types and costs of private health insurance available to the U.S. population. The survey is unparalleled in its degree of detail, as well as its ability to link medical care use, payments, and health insurance coverage to specific survey respondents and their families. It allows analysts to examine how individual and family characteristics, including the characteristics of their health insurance, affect medical care use and spending. This article discusses each of the MEPS components, focusing on design enhancements that have been made since the survey was last conducted nearly a decade ago.
Journal Article
Encouraging Preventive Services for Low-Income Children: The Effect of Expanding Medicaid
by
Short, Pamela Farley
,
Lefkowitz, Doris C.
in
African Americans
,
Ambulatory Care - economics
,
Ambulatory Care - statistics & numerical data
1992
Every year since 1984, Congress has expanded Medicaid to cover an increasing proportion of low-income children. In this study, a multivariate analysis of data from the 1987 National Medical Expenditure Survey was used to determine whether expanded Medicaid eligibility is likely to be effective in encouraging recommended preventive visits for low-income, preschool children. For low-income children who would otherwise be uninsured, a full year of Medicaid increased the probability of any well-child visits by 17 percentage points, and compliance with the guidelines of the American Academy of Pediatrics for well-child visits increased by 13 percentage points. The generosity of Medicaid fees did not alter the magnitude of these effects. However, even if all uninsured children under 200% of the poverty line were eligible for Medicaid, low-income children would continue to lag behind other children in their use of preventive services. Factors other than insurance and income, such as the lower educational attainment of low-income mothers, explain approximately 80% of the gap between children above and below 200% of poverty. The rate of compliance with the American Academy of Pediatrics guidelines was less than 50% for all preschool children. Departures from the recommended schedule of visits were particularly pronounced in the second year of life and may interfere with children receiving the recommended immunizations in a timely manner.
Journal Article
Peroxidase-mediated Oxygenation and Microbicidal Activity
by
Gnade, Brian
,
Lefkowitz, Stanley S.
,
Vigerust, David J.
in
hydrogen peroxide
,
reactive oxygen intermediates
2000
It is known that a peroxidase, H sub(2)O sub(2), and a halide form a \"cytotoxic triad.\" As a result of the interactions of the components of the triad, reactive oxygen intermediates (ROI) are formed that help to destroy various invading pathogens including Candida. The present study was undertaken to determine if equivalent units of peroxidase induced equivalent levels of macrophage-mediated killing of Candida. Murine peritoneal macrophages were exposed to various concentrations of eosinophil peroxidase (EPO), myeloperoxidase (MPO), and horseradish peroxidase (HRP). Luminol-dependent chemiluminescence studies showed that equivalent units of peroxidase, as determined by oxidation of guaiacol, demonstrated a hierarchical pattern of ROI production. Macrophage phagocytosis and candidicidal activity, as measured by a fluorescence acridine orange assay, also demonstrated the same hierarchical pattern of EPO > MPO > HRP. Therefore, enzymatically equivalent peroxidases do not demonstrate equivalent candidicidal activity. These data indicate a distinct order of peroxidases relative to their ability to stimulate chemiluminescence and macrophage-mediated killing.
Journal Article
PREVENTIVE CARE IN A VETERANS ADMINISTRATION CONTINUITY CLINIC
1990
Low levels of compliance with established guidelines for preventive care have been documented in a variety of settings. Although the Veterans Administration (VA) is the largest health care provider in the United States, data concerning preventive care to veterans is lacking. A study was conducted to examine preventive care in a university affiliated VA continuity care clinic staffed by resident physicians. Recognized guidelines were used to generate criteria specifying appropriate periodic health examinations and preventive procedures. A random sample of patients followed in the Baltimore VA Primary Care Clinic was reviewed. Compliance was highest for the traditional elements of the periodic health examination. Over 85% of patients had received histories and physical examinations, complete blood counts, electrolytes, chest radiographs, urinalyses, weight measurements, blood pressure determinations and electrocardiograms. Compliance was lower for cholesterol determination (51%) and for cancer screening procedures. Of appropriately selected patients, 19% had sigmoidoscopies, 44% rectal examinations, 50% PAP smears, and 17% mammograms. Lowest compliance was seen for influenza immunization. Only 12.5% of high risk males and 0% of high risk females had received the vaccine. Compliance did not consistently vary by duration of clinic enrollment, age, race, or sex. Efforts must be made to improve compliance with established guidelines for preventive care.
Journal Article