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Biomedical subjects

F D Moore

Publications and source records attributed to F D Moore.

At least 19 recordsLinked to original sources
PubMed1992

Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.

We examined the role of C activation in ischemia reperfusion injury by inhibiting C activation in a rat model of mesenteric arterial occlusion. In anesthetized rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion. PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v. Controls underwent laparotomy without ischemia. Relative serum C activities were assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte) sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal mucosal injury by histologic grading, lung vascular permeability by the ratio of bronchoalveolar lavage to blood concentration of radiolabeled BSA, and endothelial cell injury was quantified by measurement of plasma factor VIII-related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05)) and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/- 0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS-treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs 0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x 10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before reperfusion or at reperfusion reduced the lung permeability (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75, respectively (both p less than 0.05)) compared to PBS control, but did not reduce lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity. In this model, C is a major mediator of intestinal injury and extraintestinal injury.

Animals↗
PubMed1992

Peripheral blood neutrophils in chronically neutropenic patients respond to granulocyte-macrophage colony-stimulating factor with a specific increase in CR1 expression and CR1 transcription.

Chronically neutropenic patients from a phase I/II protocol were studied for neutrophil (PMN) abnormalities related to therapeutic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). We analyzed phenotype by flow cytometry to measure indirect immunofluorescent staining and activation of transcription by in situ hybridization. PMN count increased in seven of 17 patients. For the group, PMN expression of complement receptors, CR1 and CR3, increased after GM-CSF administration (P less than .005), while expression of class 1 and FcR III was stable. PMN from both of the patients studied by in situ hybridization demonstrated increased expression of CR1 transcript, which in one case coincided in time and intensity with the course of increased CR1 expression, while in the second case the presence of CR1 mRNA increased but lagged behind the increased CR1 protein expression. Thus, PMN activation was observed after GM-CSF infusion, as indicated by increased complement receptor expression. This effect was due both to translocation of receptors from a preformed intracellular pool to the cell surface, and to transcriptional regulation leading to increased receptor synthesis.

Antigens, Surface↗
PubMed1992

Radiation burdens for humans on prolonged exomagnetospheric voyages.

The severity of radiation exposure for astronauts outside the magnetosphere poses a critical unanswered question bearing on the use of manned vehicles in extended exploration of the solar system (moon, Mars). Such prolonged exomagnetospheric voyages (1-3 years) enter a radiologic environment more severe than that of low earth orbit, an annual dose equivalent in the range of 0.3-0.5 Sv (30-50 rem), and a lifetime excess cancer fatality risk of 3-5% due to low linear-energy-transfer components of galactic cosmic radiation alone. To this calculus must be added estimates for high-atomic-number, high-energy particles, the probability of solar particle events, and the limited effectiveness of shielding. For a 3-year Mars voyage these could elevate the dose equivalent to 1.5-2.25 Sv (150-225 rem) total (0.5-0.75 Sv [50-75 rem] annual) and risks to 5-9% excess cancer fatality. Both the mission (civilian scientific research) and the alternatives (unmanned robotic devices) enter the policy decision here. This paper presents a brief review of pertinent physical and biological data and of research urgently needed before reaching a decision on this question.

Body Burden↗
PubMed1992

Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion.

Lower torso ischemia and reperfusion leads to both local and remote tissue injuries. The purpose of this study was to assess the role of complement in mediating the local and remote microvascular permeability after bilateral hind limb tourniquet ischemia. Four hours of ischemia and 4 hours of reperfusion produced an increased skeletal muscle permeability index (muscle/blood 125I albumin ratio) of 2.90 +/- 0.35 compared with the index in nonischemic muscle of 0.25 +/- 0.02 (p < 0.01). Muscle wet-to-dry-weight ratio increased from 3.93 +/- 0.04 in sham to 5.55 +/- 0.09 in ischemic muscle (p < 0.0001). Lung permeability rose at 4 hours as indicated by the increased bronchoalveolar lavage (BAL)/blood 125I albumin ratio 4.36 +/- 0.41 x 10(-3) versus sham 2.64 +/- 0.28 x 10(-3) (p < 0.05) and neutrophil sequestration 0.28 +/- 0.02 U/g myeloperoxidase (MPO) versus sham 0.14 +/- 0.02 U/g (p < 0.001). Serum lytic activity of the classical but not the alternate complement pathway was reduced. The soluble complement receptor (sCR1) was used to inhibit complement activity and attenuated the increase in the permeability index after reperfusion in ischemic muscle 1.11 +/- 0.08 (p < 0.01) and reduced the lung BAL/blood 125I albumin ratio to sham levels 2.46 +/- 0.39 x 10(-3) (p < 0.05) at 6 mg/animal, without reducing the lung neutrophil sequestration, 0.24 +/- 0.02 U/g. The authors conclude that complement activation occurred during tourniquet ischemia and mediated permeability changes in the ischemic muscle and the lungs during reperfusion.

Albumins↗
PubMed1992

Growth analysis by the first, second, and third derivatives of the Richards function.

The Richards function serves as a tool for growth (W) analysis by means of absolute growth rate (AGR), i.e. dW/dt, and relative growth rate (RGR), i.e. d(loge W)/dt. More information may be gained using the second derivative d2W/dt2, and the third derivative d3W/dt3 of the Richards function to determine the times when the second derivative time curve achieves a maximum, minimum, and zero. The latter separates growth acceleration and retardation. Exponential growth occurs as long as (RGR)2 is less than the relative acceleration rate added to a tolerance value. This period of growth does not extend to the point of maximum acceleration of the growth curve. The points of maximum and minimum acceleration are at equal time distances from the point of inflection. A straight line phase of growth is approximated between the times when d2W/dt2 is maximum and minimum. Thus, a mathematical model for the analysis of aging changes is presented. Methodology described here should be applicable to any biological system or subsystem. As an application, derivatives of the Richards function are used to provide information on potato (Solanum tuberosum L.) tuber kinetics.

Growth↗
PubMed1991

CRRP: a guinea pig protein, identified by sequence homology to human CR1, which contains two short consensus repeat motifs and appears not to be transmembrane or secreted.

cDNA from the C4b-binding site of the human C3b/C4b receptor (CR1) was used to find homologous sequences in the guinea pig. This cDNA identified an 18S mRNA species in guinea pig spleen, but not liver. Probing of a guinea pig spleen cDNA library identified clones with identical 1.5-kb inserts, which also hybridized to mRNA in spleen, but not liver. Sequence analysis of the insert revealed a single long open-reading frame coding for a 20,000 Mr protein consisting of two short consensus repeat motifs homologous to human CR1, and unique sequence at the amino- and carboxy-terminals of the short consensus repeats. This sequence did not encode peptides with features of transmembrane domains or signal peptides. Antibody to this complement receptor-related protein-beta galactosidase fusion protein recognized a 20,000 Mr protein in SDS lysates of guinea pig spleen, lymph node, lymphocytes, neutrophils, and peritoneal macrophages. Immunoprecipitation of human serum by this antibody revealed an 180,000 Mr protein reacting both with the anti-guinea pig protein antibody and with anti-human CR1 antibody. Immunoprecipitation of guinea pig serum revealed no protein reacting with the anti-guinea pig protein antibody. Tissue staining of cultured peritoneal macrophages with this antibody showed intracellular staining, as opposed to membrane staining obtained with anti-guinea pig Ig antibody. The lack of membrane expression was confirmed by surface protein radiolabeling experiments and by fluorescent staining of surface proteins. Thus, we have identified a guinea pig protein with homology to human CR1, which may have an unusual property for this class of proteins in that it appears to be intracellular.

Amino Acid Sequence↗
PubMed1991

The systemic complement activation caused by interleukin-2/lymphokine-activated killer-cell therapy of cancer causes minimal systemic neutrophil activation.

Twenty-three cancer patients undergoing therapy with interleukin-2 and lymphokine-activated killer cells were studied for evidence of complement activation and systemic neutrophil activation occurring during the course of therapy. Patient plasma samples demonstrated evidence of marked complement activation, with 3-fold elevations of C3a desArg concentrations by the 8th day of therapy. Concentrations of C4a desArg were also elevated by the end of therapy. In vitro chemotaxis of patients' neutrophils both to C5a and to the synthetic peptide chemotaxin, FMLP, was initially normal and then fell progressively to 60% of normal by the end of treatment. Mean neutrophil cell-surface expression of complement receptor Type 1 and complement receptor Type 3 increased in inverse temporal relationship to the deficit in chemotaxis, but showed no consistent pattern for individuals and was only doubled at maximum. Thus, despite a degree of complement activation which should have produced pronounced neutrophil activation, the response of the circulating neutrophils was diminished. In view of this discrepancy, the toxicity of this therapy may not be mediated by activation of circulating neutrophils.

Chemotaxis, Leukocyte↗
PubMed1991

Board-certified physicians in the United States, 1971-1986.

BACKGROUND: This is our third report covering the census of U.S. physicians over a 15-year period. The present report updates the information for 1980 to 1986. METHODS: Most of our data are based on published information from the Association of American Medical Colleges, the Educational Council for Foreign Medical Graduates, the American Board of Medical Specialties, and the National Resident Matching Program. Data on board-certified physicians were obtained from the Division of Survey and Data Resources of the American Medical Association and are not published elsewhere. RESULTS: After a steep rise in the 1970s, the annual number of physicians receiving licenses increased at a slower rate. The numbers of new board diplomas in medicine and primary care continued to grow. In other non-surgical clinical specialties there was less growth, and in certain fields of surgery the numbers declined. The board-certified percentage of all practitioners increased slightly (74 to 79 percent). About 14 to 16 percent of all active physicians are still in their residency and fellowship years. The percentage of all practitioners under the age of 35 who are women has increased from 8.4 percent in 1967 to 25.2 percent in 1986. The enrollment of some residency programs is currently more than 50 percent women. CONCLUSIONS: The work force of physicians did not grow as rapidly in the 1980s as in the 1970s. This nonlinearity of growth and massive changes in the epidemiology and treatment of disease render predictions about the need for or the numbers of physicians a decade hence unreliable.

Certification↗
PubMed1991

Tumor necrosis factor and endotoxin can cause neutrophil activation through separate pathways.

We investigated the possibility that tumor necrosis factor (TNF) mediates neutrophil activation by endotoxin. The number of C3b receptors on the neutrophil cell-surface was used as the indicator of activation, as assessed by indirect immunofluorescence. Incubation of buffy-coat neutrophils with TNF-alpha for 30 minutes at 37 degrees C caused neutrophil activation, increasing C3b receptor-dependent fluorescence from 340 with buffer alone to 580 with TNF (250 pg/mL). Increasing amounts of anti-TNF IgG progressively inhibited neutrophil activation by TNF (250 pg/mL). Addition of the active dose range of anti-TNF to neutrophils incubating in endotoxin (10 ng/mL) did not affect the degree of endotoxin-mediated neutrophil activation. Mixtures of neutrophils with the 50% suppressive dose of anti-TNF and varying endotoxin concentrations showed the same degree of neutrophil activation as mixtures without the antibody. Thus, an antibody that can inhibit TNF-mediated neutrophil activation does not inhibit endotoxin-mediated neutrophil activation. We conclude that endotoxin and TNF can activate neutrophils through separate pathways.

Antibodies↗
PubMed1990

Coronary heart disease in Massachusetts: the years of change (1980-1984).

During this decade, diagnosis and treatment of coronary heart disease (CHD) have become far more aggressive and invasive than in prior decades. This study documents rates of hospitalization, use of various treatment options, a case fatality in the state of Massachusetts during 4 of the first 5 years of this decade (1980, 1982, 1983, and 1984). The data base was that of the Massachusetts Health Data Consortium (MHDC), covering all hospital discharges in the state, a total of 3.8 million discharge records for this period. Of these, about 190,000 (5%) fell into two active symptomatic categories of CHD: chronic active coronary disease (CACD) and acute myocardial infarction (AMI). Total hospitalization rate for these CHD categories increased by 17%; this was due both to an increased rate of hospital transfers (or readmissions) and to a larger cohort of patients under care. The case fatality rate for hospitalized CHD decreased approximately 16%, from 9.7% (1980) to 8.1% (1984). In CACD the frequency of coronary angiography (CA) rose; the use of percutaneous transluminal coronary angioplasty (PTCA) increased much faster than the rate of coronary artery bypass grafting (CABG), with a resultant increase in PTCA as a fraction of total interventions. Similar findings were recorded for AMI, but with much more marked changes, the total intervention rate increasing almost twenty-fold from 1980 to 1984. The statewide mortality rate for hospitalized CHD patients remained essentially unchanged at 71 to 74 hospital deaths per 100,000 population.

Angiography↗
PubMed1989

Monocyte activation after burns and endotoxemia.

We describe the settings in which monocytes (M) are activated, as monokines may mediate organ dysfunction occurring after surgery and sepsis. To monitor M activation, we measured the relative number of M cell surface receptors for C3b and iC3b by indirect immunofluorescence. M exposed to increasing concentrations of endotoxic lipopolysaccharide (LPS) expressed increased mean cell surface C3b receptor-dependent fluorescence (35 buffer alone vs 354 LPS at 1000 ng/ml) and iC3b receptor-dependent fluorescence (78 vs 404). To determine whether this M activation could be reproduced by endotoxemia, normal volunteers were randomly administered saline or a single dose of LPS (20 u/kg). We found increased M cell surface C3b receptors 4 hr after LPS (341 LPS (n = 22) vs 168 saline (n = 20)) which returned to control levels at 24 hr. A similar transient increase was seen at 4 hr with M cell surface iC3b receptors (304 LPS (n = 23) vs 104 saline (n = 20)). To determine whether this could be used clinically, seven patients with burns (10-70% body surface area) were serially sampled up to 50 days. Each patient demonstrated elevations of M cell surface C3b and iC3b receptors, which gradually decreased over many weeks. For the group as whole, mean M cell surface C3b receptor-dependent fluorescence was 287, Days 0-5 postburn (vs 132 in 147 normals); 315, Days 6-9; 217, Days 10-13; 237, Days 14-19; and 185, Days 20+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Recombinant human tumor necrosis factor increases granulocyte cell-surface complement receptor number.

Exposure of human buffy-coat granulocytes to tumor necrosis factor (TNF) produced cellular activation as indicated by an increase in the neutrophil and monocyte cell-surface number of C3b receptors (measured by indirect immunofluorescence). The degree of receptor increase depended on the dose of TNF from 25 to 1250 pg/mL. Results of kinetic analysis confirmed this response: TNF, 250 pg/mL, caused an increase in the C3b receptor number within ten minutes. Purified neutrophils exhibited a similar increase in cell-surface C3b receptors dependent on the concentration of TNF. Tumor necrosis factor could be a mediator of granulocyte activation in patients.

Granulocytes↗