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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 397 records · Page 22Linked to original sources
PubMed1987

Species heterogeneity in macrophage expression of the CD4 antigen.

The CD4 antigen is expressed on T cells of all mammalian species examined and appears to play an important role in the response of T cells to antigen. In humans, the molecule acts as a receptor for the AIDS virus. Previous studies have demonstrated that M phi in the rat and human also express the CD4 antigen, which is indistinguishable from that on T cells. In this paper we demonstrate by FACS analysis, Northern blot hybridization, and immunoperoxidase labeling that, in striking contrast to the rat and human, mouse M phi do not express the CD4 (L3T4) antigen. This species heterogeneity indicates that T cells and M phi regulate CD4 antigen expression independently and that CD4 may not be essential for M phi function.

Animals↗
PubMed1987

The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration.

Using mAbs and immunocytochemistry we have examined the response of macrophages (M phi) after crush injury to the sciatic or optic nerve in the mouse and rat. We have established that large numbers of M phi enter peripheral nerves containing degenerating axons; the M phi are localized to the portion containing damaged axons, and they phagocytose myelin. The period of recruitment of the M phi in the peripheral nerve is before and during the period of maximal proliferation of the Schwann cells. In contrast, the degenerating optic nerve attracts few M phi, and the removal of myelin is much slower. These results show the clearly different responses of M phi to damage in the central and peripheral nervous systems, and suggest that M phi may be an important component of subsequent repair as well as myelin degradation.

Animals↗
PubMed1987

Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages.

The concentrations of ATP and the ATP/AMP concentration ratios were maintained in thioglycollate-elicited mouse peritoneal macrophages incubated in vitro for 90 min in the presence or absence of added substrate: rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 60 min of incubation. The rate of oxygen consumption by macrophages was only increased above the basal rate (i.e. that in the absence of added substrate) by addition of succinate or pyruvate, or by addition of the uncoupling agent carboxyl cyanide m-chlorophenylhydrazone ('CCCP'); it was decreased by 75% by the addition of KCN. These findings suggest that metabolism of endogenous substrate can provide most, if not all, of the energy requirement of these cells, at least for a short period. The rates of glucose and glutamine utilization by incubated macrophages were approx. 300 and 100 nmol/min per mg of protein respectively. A large proportion of the glutamine that is utilized is converted into glutamate and aspartate, and very little (perhaps less than 10%) is oxidized. Similarly almost all of the glucose that is utilized is converted into lactate and very little is oxidized. This characteristic is similar to that of resting lymphocytes and rapidly dividing cells; in non-proliferating macrophages it may be a mechanism to provide precision in control of the rate of biosynthetic processes that utilize intermediates of these pathways, e.g. purines and pyrimidines for mRNA for the synthesis of secretory proteins and glycerol 3-phosphate for phospholipid synthesis for membrane recycling. No utilization of acetoacetate or 3-hydroxybutyrate by macrophages was detected. In contrast, both butyrate and oleate were oxidized. The rate of [14C]oleate conversion into 14CO2 (1.3 nmol/h per mg of protein) could account for most of the oxygen consumption by incubated macrophages, suggesting that long-chain fatty acids might provide an important fuel in situ. This may be one explanation for the secretion of lipoprotein lipase by these cells, to provide fatty acids for oxidation from the degradation of local triacylglycerol.

Adenine Nucleotides↗
PubMed1987

Computer-based instruction in clinical medical education: a pulmonary medicine self-assessment.

This computer assisted teaching program was designed to provide a comprehensive review of pulmonary medicine in the form of a self-assessment. The program consisted of 30 questions including multiple choice, true or false and matching questions. The questions were based on the respiratory chapter from a standard textbook of medicine. Forty students taking their mandatory medicine rotation at a major university teaching hospital used the program. Their scores ranged from 46.7% to 93.3% with a mean of 68.1%. The format enabled the student to answer the questions, to quickly determine which ones he got right and wrong and then he was provided with the correct answer and a reference in the respiratory chapter of the standard textbook of medicine on which the assessment was based. A score was given to each individual so that each student could be his own judge as to how well he did. After reading the references for the questions missed, the learner would decide for himself what area of pulmonary medicine deserved further study.

Computer-Assisted Instruction↗
PubMed1987

Computer assisted teaching program: a pulmonary patient management problem.

The use of computer assisted teaching in medical school could be a valuable adjunct to the more traditionally employed backboard and slides. A computer program based upon a pulmonary patient management simulation was developed to teach and assess pulmonary management skills of junior medical students. Over the period of 18 months, 39 medical students taking their internal medicine rotation at a core teaching hospital used the program. The scores ranged from 45 to 100 with a mean of 74.9%. The participants were awarded points for good clinical decisions and were penalized points for poor clinical decisions. Student evaluation of the program was highly encouraging supporting the value of computer assisted teaching. When the clinical simulation program was used in our learning resource laboratory, it promoted a high level of student-computer interaction and facilitated problem based learning. Our computer assisted teaching program using a pulmonary patient problem as its core was a valuable tool for self assessment and independent study of pulmonary medicine and it effectively complemented traditional modes of teaching medical education.

Computer Simulation↗
PubMed1987

Treatment of cryptosporidiosis with oral bovine transfer factor.

Cryptosporidia are intestinal protozoans long known to cause diarrhea in humans, especially those with acquired immune deficiency syndrome (AIDS). When transfer factor prepared from calves which possessed delayed-type hypersensitivity to Eimeria bovis was given to nonimmune calves and mice it conferred protection against clinical infection (coccidiosis). Recent studies with oral bovine transfer factor have shown that it can confer cell-mediated immunity to humans. Based on these findings we decided to treat eight AIDS patients suffering from Cryptosporidium-associated diarrhea with transfer factor prepared from calves immune to Cryptosporidium. Prior to treatment with transfer factor, three patients had been treated with spiramycin, one patient with alpha-difluoromethylornithine (DFMO), and one patient with furazolidone for greater than 1 month without clinical or laboratory improvement. Following administration of transfer factor, five or eight patients exhibited a decrease in the number of bowel movements and the development of formed stools. Cryptosporidium was eradicated from the stools of four patients but two of these patients subsequently relapsed and one patient continued to have diarrhea despite the absence of Cryptosporidium in the stool. One patient has been free of diarrhea and Cryptosporidium for 2 years after discontinuation of transfer factor therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Surface events in polymorphonuclear leucocyte activation: insights from a hydrophobic membrane antigen that triggers the respiratory burst.

The rat monoclonal antibodies (Mab) 1A10.4 and IG4 were raised to a solubilized NADPH-oxidase preparation from guinea-pig polymorphonuclear neutrophils (PMN). They bind to a surface antigen restricted to guinea-pig myelomonocytic cells and on binding to the PMN surface can stimulate the respiratory burst (RB) and degranulation. This response was specific to these Mab and was not found with several other Mab restricted to myelomonocytic cells but with other antigenic epitopes. In order to understand the role of this molecule in stimulating the RB, we have characterized the antigen (Ag) by a variety of techniques. It is a hydrophobic membrane molecule with an apparent molecular weight of 8-10(x10(3] and a pI of 6.2. The Ag has been partially purified by extraction in organic solvents and high-pressure liquid chromatography on silica and is probably a proteolipid. Studies on Mab-dependent triggering of PMN secretion indicated that cross-linking of the cell surface was critical. We therefore used direct immunofluorescence under triggering and non-triggering conditions to show that stimulation of the RB by Mab correlated with redistribution of the surface Ag into patches. This patching was associated with aggregation of surface Ag and transfer of Ag from a Triton X-100-extractable to a Triton X-100-inextractable membrane domain. These movements of surface Ag, which included both patching and capping resulting from aggregation of a hydrophobic membrane component, occurred at 4 degrees C and were insensitive to inhibition by cytoskeletal inhibitors. These specific probes that control triggering of the RB have permitted the dissection of PMN stimulation into discrete membrane events by correlating the biochemical and morphological characteristics of a new PMN surface Ag as it stimulates exocytosis.

Animals↗
PubMed1987

A second Australian family with hemoglobin North Shore (beta 134 Val----Glu).

A second Australian family is reported with Hemoglobin North Shore (beta 134 Val----Glu), an unstable hemoglobin, causing no clinical symptoms. All affected family members showed only mild reticulocytosis and microcytosis on the blood film, despite the strongly positive isopropanol test for Hb (hemoglobin) stability and numerous red cell inclusions. Hb North Shore constituted 31-38% of the total hemoglobin and migrated on the anodal side of Hb A at pH 8.9. The association of a mildly raised Hb A2 level and thalassemic phenotype with Hb North Shore previously reported, is confirmed in this study.

Adult↗
PubMed1987

Protein C abnormalities in spinal cord injured patients with end-stage renal disease.

Patients with chronic spinal cord injury (SCI) and end-stage renal disease (ESRD) exhibit antithrombin III deficiency and several other coagulation abnormalities. In view of increasing recognition of protein C (PC) as an important, naturally occurring anticoagulant and fibrinolytic factor, we studied plasma PC in this population. PC antigen concentration and its anticoagulant activity were measured in nine SCI men with ESRD maintained on hemodialysis and in a control group of ten normal able-bodied men. The results showed a significant increase in PC anticoagulant activity in the SCI group. Consequently, the ratio of the PC activity to its concentration, which is a measure of the functional integrity of PC molecule, was markedly depressed. These findings are indicative of the presence of inactive or abnormal PC in SCI-ESRD patients and may suggest its in vivo activation. The combination of impaired PC activity shown in this study, with previously demonstrated antithrombin III deficiency and other coagulation abnormalities, is suggestive of a hypercoagulable state.

Adult↗
PubMed1987

The mouse macrophage-specific glycoprotein defined by monoclonal antibody F4/80: characterization, biosynthesis and demonstration of a rat analogue.

F4/80, a mouse macrophage-specific membrane marker defined by a rat monoclonal antibody, was precipitated by a rabbit antiserum raised against partially purified mouse antigen. The antiserum, when tested against a variety of mouse tissues and cells, bound only to, and was cytotoxic for, macrophages, and it precipitated a similar macrophage-specific protein from rat cells. The F4/80 antigen is a glycoprotein of apparent molecular weight (MW) 150,000, and was labelled biosynthetically with [14C]glucosamine. Neuraminidase treatment removed small amounts of sialic acid, and tunicamycin and 2-deoxyglucose both inhibited antigen synthesis. Pulse/chase labelling with [35S]methionine demonstrated a precursor of 110,000 MW. Proteinase treatment of intact cells cleaved the molecule to an initial 100,000, and then to an 80,000 MW fragment. Without reduction, the MW of the molecule was unchanged by proteinases. These studies indicate that the F4/80 antigen consists of at least two domains linked by disulphide bridges, of MW 80,000 and 20,000. Both domains are extracellular.

Animals↗
PubMed1986

Properties and distribution of a lectin-like hemagglutinin differentially expressed by murine stromal tissue macrophages.

We describe a novel hemagglutinin which is differentially expressed on murine stromal tissue macrophages. Resident bone marrow macrophages (RBMM), which are physically associated with immature, proliferating hematopoietic cells in vivo, formed striking rosettes with unopsonized sheep erythrocytes (E) in vitro, unlike resident peritoneal macrophages (RPM). Binding of E was macrophage (M phi) specific, not accompanied by ingestion and independent of temperature (0-37 degrees C), divalent cations, and the metabolic inhibitors azide and iodoacetate. Pretreatment of RBMM with trypsin prevented rosette formation, but neuraminidase enhanced it. Conversely, binding was virtually abrogated if E were pretreated with neuraminidase, whereas trypsin pretreatment of the ligand resulted in a slight enhancement. The lectin-like nature of the E receptor (SER), with specificity for sialylated glycoconjugates, was consistent with the inhibition of binding we saw with neuraminyllactose or the ganglioside GD1a (50% inhibition at 5-10 mM and 11 microM, respectively). Expression of SER on freshly isolated RBMM was heterogeneous and exhibited a striking inverse correlation with expression of Ia antigens. During cultivation in 10% FCS, levels of SER on RBMM declined with a half-life of approximately 24 h. Other cell surface changes induced by cultivation included a transient increase in expression of Ia antigen and acquisition of Mac-1. To determine whether SER was expressed on other stromal M phi populations, adherent cells were isolated from various tissues by collagenase digestion or lavage. Binding of E was highest on RBMM and lymph node stromal M phi, at intermediate levels on Kupffer cells and splenic stromal M phi, but was low or undetectable on blood monocytes and thymic, peritoneal, pleural, and bronchoalveolar M phi. SER therefore appeared to be expressed on certain M phi populations embedded in solid tissues but was largely absent from M phi recoverable by lavage. Its absence from monocytes implies that SER is acquired by M phi after entering tissues where it may perform adhesive functions. In bone marrow, SER on RBMM could interact with an appropriate sialylated ligand on murine hematopoietic cells, and could influence their rate of growth and differentiation.

Animals↗
PubMed1986

Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages.

Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.

Animals↗
PubMed1986

Interferon alpha/beta selectively antagonises down-regulation of mannosyl-fucosyl receptors on activated macrophages by interferon gamma.

Previous reports have described synergism of various interferon preparations in anticellular and antiviral activity. We report that recombinant interferon (rIFN gamma) and IFN alpha/beta mediate distinct, antagonistic effects on expression of a lectin-like receptor for mannose and fucose (MFR) on mouse peritoneal macrophages (M phi). IFN gamma down-regulates MFR activity, a highly reproducible change in mouse M phi activated to secrete enhanced levels of o-2/H2o2. IFN alpha/beta enhances MFR activity and prevents the action of IFN gamma when added in combination. Antagonism is selective for this M phi activation marker and requires a minimum 4 h exposure period to rIFN gamma, during which IFN alpha/beta can prevent its action.

Animals↗
PubMed1986

A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty for acute myocardial infarction.

We randomly assigned 56 patients who presented within 12 hours of their first symptoms of acute myocardial infarction to treatment with either intracoronary streptokinase or coronary angioplasty. The mean (+/- SD) duration of symptoms (3.0 +/- 1.2 hours in the group treated with angioplasty vs. 3.6 +/- 1.8 in the group treated with streptokinase; P not significant) and time to recanalization (4.1 +/- 1.4 hours vs. 4.8 +/- 1.7 hours; P not significant) were similar in both groups. Coronary recanalization was achieved in 83 percent of the patients treated with angioplasty and in 85 percent of those treated with streptokinase (P not significant). Residual luminal stenosis in the coronary artery was significantly decreased after angioplasty, as compared with streptokinase therapy (43 +/- 31 percent of patients vs. 83 +/- 17; P less than 0.001). Residual stenosis of 70 percent or more was present in 4 percent of the angioplasty-treated patients and in 83 percent of the streptokinase-treated patients (P less than 0.01). Ventricular function after therapy was assessed by serial contrast ventriculograms. Increases in both global ejection fraction (8 +/- 7 percent vs. 1 +/- 6; P less than 0.001) and regional wall motion (+1.32 +/- 1.32 SD vs. +0.59 +/- 0.79 SD; P less than 0.05) were greater for the angioplasty group. We conclude that angioplasty and streptokinase produce similar rates of early coronary reperfusion during evolving transmural myocardial infarction. However, angioplasty is significantly more effective in alleviating the underlying coronary stenoses, and this may result in more effective preservation of ventricular function after therapy.

Angiography↗
PubMed1986

Macrophage plasma membrane and secretory properties in murine malaria. Effects of Plasmodium yoelii blood-stage infection on macrophages in liver, spleen, and blood.

We have studied the effect of infection with the blood-stage of Plasmodium yoelii 17X, a nonlethal parasite, on plasma membrane antigens, receptors, and secretory properties of macrophages (M phi) in murine liver, spleen, and blood. mAb F4/80 (M phi specific), F7/4 (a marker for immature and immunologically activated M phi, as well as neutrophils), and Mac-1, which binds to the type 3 complement receptor, were used to measure the distribution and total content of antigens in situ and to assay surface expression of antigens on M phi isolated by collagenase perfusion-digestion and adherence. We also examined respiratory burst activity after stimulation with PMA, FcR activity, Ia antigen expression, and binding of 125I-mannose-BSA and unopsonized sheep erythrocytes by isolated M phi. In the normal animal, spleen M phi expressed Mac-1 and F7/4 antigens and relatively high levels of respiratory burst activity, in contrast to Kupffer cells in liver, where all three features were virtually absent. The introduction of parasitized erythrocytes into the circulation resulted in a large influx of F4/80+ M phi into the blood, liver, and spleen, where local M phi proliferation could also contribute. Liver M phi during malaria infection showed increased Mac-1 and 7/4 antigen and an increased respiratory burst potential compared with uninfected controls. Increases in total, but not specific activity of FcR, Ia antigen, and binding of unopsonized sheep erythrocytes were found in spleen and liver M phi populations after infection. In both populations, there was an early but persistent marked reduction in specific binding and uptake of 125I-mannose-BSA. These results confirm and extend observations that normal Kupffer cells are relatively homogeneous in morphology, surface markers, and anatomical location, in contrast to M phi in normal spleen, and that both of these populations differ from resident M phi elsewhere, including the peritoneal cavity. In the course of infection by P. yoelii, M phi with high levels of opsonic receptors (CR3, FcR) and respiratory burst potential are mobilized in large numbers at specific sites such as liver and spleen, in accordance with an important role for M phi in the clearance of parasitized erythrocytes from blood.

Animals↗
PubMed1986

Localization and function of tissue macrophages.

The rat monoclonal antibody F4/80 defines a plasma membrane glycoprotein of about 160 kilodaltons that is expressed by mature mouse macrophages. The antigen has been used to define macrophage distribution within the mouse (normal adult, embryo, infection models) by cytochemistry and quantitative immunochemical analysis. Macrophages migrate into fetal and adult haemopoietic and other tissues in an ordered sequence. The surface properties of 'fixed' macrophages isolated from various organs (bone marrow, liver, spleen) are distinct from those of circulating monocytes or free cells (peritoneal and pleural cavities, alveolar) and may play a role in local adhesion and trophic interactions with other cells.

Animals↗
PubMed1986

Interaction and regulation of macrophage receptors.

Macrophages express distinct plasma membrane receptors for different isotypes of immunoglobulin, bear at least two receptors for cleaved third complement component (CR1 and CR3) and have a lectin-like receptor that mediates endocytosis of glycoproteins or glycoconjugates with terminal mannose or fucose residues (MFR). Interferon-gamma, a macrophage-activating factor, induces effects common to other interferons as well as having unique effects on cell function. The down-regulation of MFR, induction of IgG2a Fc receptors and Class II antigens and enhanced production of superoxide and hydrogen peroxide can be considered interferon-gamma-specific effects on macrophages. Previous reports described synergism of various interferon preparations in anticellular and antiviral effects. However, interferon-alpha/beta can selectively antagonize the down-regulation of macrophage MFR by interferon-gamma. The macrophage MFR and CR3 also play a synergistic role in the uptake of zymosan and Leishmania donovani in the absence of serum. The receptors may act independently or in concert. Cleaved third complement components can be specifically eluted from zymosan particles in the absence of exogenous complement and are derived from the macrophages themselves. These studies indicate a role for macrophage complement in local opsonization of pathogens at extravascular sites and focus on the role of the tissue macrophage in first-line host defence.

Animals↗