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S Gordon

Publications and source records attributed to S Gordon.

At least 343 records · Page 19Linked to original sources
PubMed1991

Adhesion receptors involved in the erythroblastic island.

We have defined two receptors involved in the binding of erythroblasts and other developing hematopoietic cells to murine macrophages. With 14-day-old fetal liver macrophages, which exclusively interact with erythroid cells in vivo, a divalent cation-dependent adhesion receptor, EbR, is able to mediate reversible attachment of erythroblasts in vitro. With adult resident bone marrow macrophages, which naturally bind a mixture of myeloid and erythroid cells, two distinct receptors are involved. Most of the binding is mediated by an EbR-like divalent cation-dependent receptor. The remainder is mediated by a divalent cation-independent receptor, SER, which was originally discovered by its ability to bind unopsonized sheep erythrocytes. To date, the molecular nature of EbR is unknown, but the failure of certain antisera and specific inhibitors to block its activity indicates that EbR may be a novel macrophage adhesion receptor. SER has recently been characterized by means of a monoclonal antibody selected on the basis of its ability to block binding of sheep erythrocytes. SER is a 185-K plasma membrane glycoprotein expressed specifically by resident bone marrow macrophages. Inhibition experiments have demonstrated that SER is able to mediate binding of erythroid and myeloid cells via recognition of sialylated glycoconjugates. The possible functions of EbR and SER in macrophage-hematopoietic cell interactions are discussed.

Animals↗
PubMed1991

Myocardial and aerobic requirements for an upper body exerciser: implications for cardiac rehabilitation.

To assess the cardiorespiratory, hemodynamic, and electrocardiograph (ECG) responses to an upper body exercise device, we studied ten cardiac men (mean age +/- SD = 58.0 +/- 6.5 years) who performed three five-minute exercise bouts at metronome settings of 20, 50, and 80 clicks per minute. Operation of the device involved shuttling a plastic buoy on two 6-m waxed ropes between two persons. Aerobic requirements were generally appropriate for arm training, corresponding to mean values of 5.3, 7.0, and 10.1 ml.kg-1.min-1 at the three progressive metronome settings. Perceived exertion (Borg, 6 to 20 scale) at these work rates was 8.3, 10.4, and 14.6, whereas average heart rate and systolic blood pressure responses were 77, 85, and 114 beats.min-1 and 145, 158, and 175 mmHg, respectively. Continuous ECG monitoring during upper body exercise revealed no significant ST-segment depression or serious arrhythmias. The device appears to be a safe and effective complement to a cardiac exercise training program.

Aged↗
PubMed1990

Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages.

Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The non-obese diabetic mouse is a good spontaneous animal model of the human disease, with IDDM developing in 50-80% of female mice by the age of 6 months. The disease can be transferred by splenic T cells from diabetic donors and is prevented by T-cell depletion. The mechanism(s) by which the beta cell is specifically destroyed is not known, but T cells and macrophages have both been implicated, based on the presence of macrophages in the infiltrated islet and the ability of chronic silica treatment to prevent disease. The monoclonal antibody 5C6 is specific for the myelomonocytic adhesion-promoting type-3 complement receptor (CR3 or CD11b/CD18) and does not bind to T cells. Here we show that blockade of macrophage CR3 in vivo prevents intra-islet infiltration by both macrophages and T cells and inhibits development of IDDM. We conclude that both T cells and macrophages have an essential role in the onset of IDDM.

Animals↗
PubMed1990

Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial.

BACKGROUND AND METHODS: Pneumocystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection associated with human immunodeficiency virus (HIV) infection. To assess the possible value of aerosolized-pentamidine prophylaxis in different doses, a controlled clinical trial was begun in 1987 with 408 subjects at 12 treatment centers. The participants were randomly assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks, or 300 mg every four weeks. RESULTS: Eighteen months after randomization, the subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had intermediate results but ones not significantly different from those of the 300-mg arm. Participants with previous episodes of PCP and CD4-cell counts less than 200 per cubic millimeter were at the highest risk for PCP. CONCLUSIONS: Aerosolized pentamidine was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.

Adult↗
PubMed1990

Ultrastructural localization of a macrophage-restricted sialic acid binding hemagglutinin, SER, in macrophage-hematopoietic cell clusters.

Resident bone marrow macrophages in hematopoietic clusters have previously been shown to express a novel lectin-like sheep erythrocyte receptor, SER, which mediates binding of unopsonized sheep erythrocytes via recognition of sialylated glycoconjugates and may interact with sialylated ligands on murine bone marrow cells. In this study, the distribution of SER on macrophages within hematopoietic clusters was localized by a monoclonal antibody, SER-4, by immunofluorescence and immunoelectron microscopy. SER was found to be diffusely localized at the contact zones between macrophages and erythroblasts, whereas the receptor was highly concentrated at the contacts between macrophages and developing myelomonocytic cells. These data suggest that SER on resident bone marrow macrophages interacts differentially with sialylated ligands on developing myeloid cells and that this may influence their development.

Animals↗
PubMed1990

Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis.

Murine thioglycollate-elicited peritoneal macrophages were cultured in the presence of a variety of fatty acids added as complexes with bovine serum albumin. All fatty acids tested were taken up readily by the cells and both neutral and phospholipid fractions were enriched with the fatty acid provided in the medium. This generated a range of cells enriched in saturated, monounsaturated or polyunsaturated fatty acids, including n-3 acids of fish oil origin. Saturated fatty acid enrichment enhanced macrophage adhesion to both tissue culture plastic and bacterial plastic compared with enrichment with polyunsaturated fatty acids. Macrophages enriched with the saturated fatty acids myristate or palmitate showed decreases of 28% and 21% respectively in their ability to phagocytose unopsonized zymosan particles. Those enriched with polyunsaturated fatty acids showed 25-55% enhancement of phagocytic capacity. The greatest rate of uptake was with arachidonate-enriched cells. Phagocytic rate was highly correlated with the saturated/unsaturated fatty acid ratio, percentage of polyunsaturated fatty acid and index of unsaturation, except for macrophages enriched with fish-oil-derived fatty acids; they showed lower phagocytic activity than expected on the basis of their degree of unsaturation. These results suggest that membrane fluidity is important in determining macrophage adhesion and phagocytic activity. However, in the case of phagocytosis, this effect may be partially overcome if the cells are enriched with fish-oil-derived fatty acids. Thus it may be possible to modulate the activity of cells of the immune system, and so an immune response, by dietary lipid manipulation.

Animals↗
PubMed1990

Solubilization and denaturation of monomeric actin from erythrocyte membranes by p-mercuribenzenesulfonate.

Solutions of p-mercuribenzenesulfonate extract the peripheral proteins from the red cell membrane in a water-soluble form. Low concentrations of the reagent selectively solubilize actin, while at higher concentrations, spectrin, ankyrin and bands 4.2 and 4.1 are extracted. After brief exposure to the reagent, followed by displacement of the mercurial with dithiothreitol or 2-mercaptoethanol, the soluble actin is capable of inhibiting DNAse I activity. With prolonged exposure or with higher concentrations of the reagent, the ability to inhibit DNAse is gradually lost. The kinetics of both the release of actin capable of DNAse inhibition and the subsequent loss of that capability are pseudo-first-order with respect to time, but show second-order dependence on the concentration of mercurial. These data suggest that dissociation of the actin from protofilaments in the cytoskeleton requires exposure of more than one sulfhydryl group to the reagent. Subsequent inactivation also appears to be dependent on the reaction of further multiple sulfhydryl groups, possibly in buried regions of the actin molecule.

4-Chloromercuribenzenesulfonate↗
PubMed1990

Validity of arm ergometer blood pressures immediately after exercise.

It is not possible to assess blood pressure (BP) by the standard cuff method during exercise primarily involving the arms. Consequently, such measurements are often taken immediately after (within 15 seconds) exercise. To assess the validity of this practice, 18 healthy men (mean age 32 years) who completed 3 progressive 3-minute workloads were studied during arm-crank ergometry. Ankle systolic BP was measured at the dorsalis pedis artery at seated rest, 15 seconds before completion of each exercise stage and immediately after each workload, using a Doppler stethoscope; simultaneous postexercise brachial systolic BPs were determined by auscultation. Brachial systolic BP during armcrank ergometry was estimated by the formula: (resting brachial systolic BP) + (exercise ankle systolic BP - resting ankle systolic BP). Brachial systolic BPs, obtained immediately after arm-crank ergometry, were significantly lower than those estimated during exercise (p less than 0.001), with corresponding mean values of 141 versus 153, 144 versus 173 and 151 versus 182 mm Hg at 150, 300, and 450 kg.m.min-1, respectively. The difference between measured (postexercise) and estimated pressures increased with progressive workloads. These findings indicate that systolic BPs taken by the standard cuff method immediately after arm-crank ergometry are likely to underestimate "true" physiologic responses.

Adult↗
PubMed1990

Tumor necrosis factor mRNA localized to Paneth cells of normal murine intestinal epithelium by in situ hybridization.

Paneth cells in normal murine small intestine contain TNF mRNA that is readily detectable by in situ hybridization, unlike resident macrophages in lamina propria, which are negative. Northern blot analysis of whole tissue shows the presence of mRNA that has the same electrophoretic mobility as TNF mRNA from activated macrophages. A low level of TNF bioactivity, but no immunoreactivity, was detected in normal small intestine, and TNF production in resting Paneth cells appears to be post-transcriptionally controlled. Typical leukocyte surface membrane markers were not found on Paneth cells, but were expressed by the surrounding lamina propria macrophages. Paneth cells are thus epithelial cells with leukocyte-like secretory potential that may be important in intestinal physiology and pathology.

Animals↗
PubMed1990

Adoptive transfer of fluorescence-labeled cells shows that resident peritoneal macrophages are able to migrate into specialized lymphoid organs and inflammatory sites in the mouse.

We have examined the migration of murine macrophages from the vascular compartment to normal and inflammatory tissues by the adoptive transfer of resident peritoneal macrophages (RPM phi) fluorescently labeled with the hydrophobic dye 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). After initial labeling of the plasma membrane of RPM phi, the dye accumulated stably in intracellular vesicles of low density (rho = 1.042-1.045 kg/l) and cells remained viable in culture for 4 weeks. Like the normal monocyte, DiI-RPM phi, but not exudate-derived or fixed cells, migrated to peritoneal exudates, following i.v. adoptive transfer, by a mechanism inhibitable by an antibody to the type 3 complement receptor. In the absence of an inflammatory stimulus there was no migration to the peritoneal cavity, and DiI-RPM phi accumulated within 4 h in the red pulp and marginal zone of the spleen. By day 6 these cells still formed a tight ring of fluorescence in the marginal zone alone, outside the marginal metallophil cells. DiI-RPM phi injected into the peritoneal cavity migrated to the parathymic lymph nodes where they were found in the subcapsular sinus and in the medullary cords, whereas very few fluorescent cells could be found in the T cell areas. The migration of RPM phi to lymphoid organs required viable cells but, unlike the recruitment of cells to peritoneal exudates, was not inhibitable by antibodies to CR3. We conclude that the RPM phi is a useful surrogate for the analysis of constitutive and induced monocyte migration to secondary lymphoid and inflammatory sites, respectively.

Animals↗
PubMed1990

Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain.

We have examined the distribution of microglia in the normal adult mouse brain using immunocytochemical detection of the macrophage specific plasma membrane glycoprotein F4/80. We were interested to learn whether the distribution of microglia in the adult brain is related to regional variation in the magnitude of cell death during development and resulting monocyte recruitment, or whether the adult distribution is influenced by other local microenvironmental cues. We further investigated the possibility that microglia are sensitive to their microenvironment by studying their morphology in different brain regions. Microglia are present in large numbers in all major divisions of the brain but are not uniformly distributed. There is a more than five-fold variation in the density of immunostained microglial processes between different regions. More microglia are found in gray matter than white. Particularly, densely populated areas include the hippocampus, olfactory telencephalon, basal ganglia and substantia nigra. In comparison, the less densely populated areas include fibre tracts, cerebellum and much of the brainstem. The cerebral cortex, thalamus and hypothalamus have average cell densities. There was no simple relationship between the amount of developmental cell death and the adult distribution of microglia. An estimate of the total number of microglia in the adult mouse brain, 3.5 x 10(6), is comparable to that found in the liver on a weight for weight basis. However, microglia possess up to twice the surface area of membrane of Kupffer cells, the large resident macrophages of the liver. The proportion of cells that were microglia varied from 5% in the cortex and corpus callosum, to 12% in the substantia nigra. Microglia vary in morphology depending on their location. They were broadly classified into three categories. Compact cells are rounded cells, sometimes with one or two short thick limbs, bearing short processes ("bristles"). They resemble Kupffer cells of the liver and are found exclusively in sites lacking a blood-brain barrier. Longitudinally branched cells are found in fibre tracts and possess several long processes which are usually aligned parallel to, or more occasionally perpendicular to, the longitudinal axis of the nerve fibres. Radially branched cells are found throughout the neuropil. They can be extremely elaborate and there is wide variation in the length and complexity of branching of the processes. There was no evidence of monocyte-like cells in the adult CNS. The systematic variation in microglial morphology provides further evidence that these cells are sensitive to their microenvironment.

Animals↗
PubMed1990

Murine immunoglobulin G anti-CD4 monoclonal antibodies bind to primary human monocytes and macrophages through Fc receptors as well as authentic CD4.

Using Western blot and fluorescence-activated cell sorter (FACS) analysis, we demonstrated that primary human monocytes and culture-derived macrophages express low levels of authentic CD4 antigen. The plasma membrane Fc receptor (FcR) on mononuclear phagocytes plays a major role in the binding of murine immunoglobulin G2 alpha anti-CD4 monoclonal antibody (MAb), and contributes to binding of other subclasses. The FcR detected shows an increase in apparent molecular weight from 60 to 70 kD over 2 weeks in culture. U937 cells resemble T lymphocytes, rather than primary monocytes/macrophages, in expressing relatively high levels of CD4; FcR contributes little to the signal. The potential bivalent interactions between immunoglobulin G and receptors such as CD4 and FcR could influence the binding and fate of HIV in primary monocytes/macrophages.

Animals↗
PubMed1990

Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population.

This study was designed to explore the incidence of lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) and their relationship to each other in a healthy population of 499 blood donors. Plasma samples were tested for LA activity and IgG, IgM and polyvalent ACA. Prolongation of the kaolin clotting time of a mixture of 80% normal plasma and 20% test plasma compared to the normal (dKCT) was used to detect LA activity. A normal distribution of dKCT was found with the mean 3.5 seconds +/- SD 10.6 seconds. Forty subjects (8%) were greater than 10% of the normal control; among these, 18 (3.6%) were outside the 95% confidence limits. The median age (29.3) and sex (M = 12, F = 28) of the 40 subjects with prolonged KCT were significantly different (p less than 0.001) from the group as a whole, younger females predominating. The frequency distribution of IgG, IgM and polyvalent ACA was skewed and the majority did not have detectable levels. ACA concentration falling within 95% of the population group were regarded as normal. Applying this definition, abnormal IgG ACA was greater than 4.33 U/ml, IgM ACA greater than 3.55 U/ml and polyvalent ACA greater than 4.55 U/ml with a prevalence of 4.6%, 4.6% and 5.6% respectively. Of the subjects with positive ACA of any class there was no significant association with either age or sex or the presence of LA. Only three plasma samples had both activities. Neither ACA nor LA were associated with antinuclear antibodies (ANA) or rheumatoid factor (Rh factor). Thus, in a healthy population LA is found predominantly in younger females and neither LA or ACA appear to identify subjects with other autoimmune parameters such as ANA or Rh factor or, for that matter, each other.

Adult↗
PubMed1990

Evidence that the Rate of Wallerian Degeneration is Controlled by a Single Autosomal Dominant Gene.

In a substrain of C57BL mice, C57BL/Ola, Wallerian degeneration in the distal segment of the severed sciatic nerve is extremely slow when compared to other mice. Despite this very slow degeneration in the distal segment regeneration of the motor nerves is not impaired. From suitable genetic outcrosses and backcrosses, the authors provide evidence that the rate of Wallerian degeneration in this strain is controlled by a single autosomal gene product. The authors have also shown that the rate of degeneration, in C57BL/Ola mice, is influenced by the environment in which the animals were bred and housed. Wallerian degeneration in the sciatic nerves of mice raised in isolators is slower than in those raised in a conventional animal house. This strain of mouse may prove to be of value in the understanding of nerve degeneration and regeneration.

Journal Article↗
PubMed1990

Evidence that Very Slow Wallerian Degeneration in C57BL/Ola Mice is an Intrinsic Property of the Peripheral Nerve.

We have described a mutant mouse, C57BL/Ola, in which Wallerian degeneration following peripheral nerve transection is very slow. Our previous results suggested that recruited monocytes play a role in rapid Wallerian degeneration. The nature of the mutation in C57BL/Ola mice is not known and we have investigated whether the defect is intrinsic to the nerve or due to a defect in the circulating monocytes. We have made chimaeric mice in which bone marrow from histocompatible mice, with rapidly degenerating nerves and normal monocyte recruitment, was used to reconstitute irradiated C57BL/Ola mice and vice-versa. A substantial degree of donor repopulation of the hosts was confirmed by measures of the levels of glucose-phosphate isomerase alloenzymes in blood and tissue samples from the two different strains. The rate of degeneration of the transected sciatic nerve was found to be host-dependent, providing evidence that the mutation affects cell populations intrinsic to the nerve and not the circulating monocytes. We provide additional evidence that the peripheral nerves of C57BL/Ola mice are different from those of other mice as they degenerate at a slower rate in vitro.

Journal Article↗
PubMed1990

The role of the type 3 complement receptor in the induced recruitment of myelomonocytic cells to inflammatory sites in the mouse.

The type 3 complement receptor (CR3), initially identified as the leukocyte cell surface receptor for iC3b, is now known to form part of the extended integrin family of cell adhesion molecules that mediate both cell-cell and cell-extracellular matrix interactions. The identification of a heritable deficiency of human leukocyte adhesion together with the advent of monoclonal antibodies has shed some light on the central role of CR3 in the transendothelial migration of macrophages and neutrophils to sites of inflammation. We review the general structural features of CR3 and then examine our understanding of its role in both nonspecific and T cell-dependent inflammatory processes based on our murine in vivo experiments. CR3-dependent inflammation seems to contribute to the pulmonary response to some stimuli (lipopolysaccharide) but not to others (bacillus Calmette-Guerin). These studies highlight the potential therapeutic benefits, as well as the significant risks of potentiating acute bacterial infections, of CR3 blockade in vivo.

Animals↗
PubMed1990

Comparison of four laboratory tests for lupus anticoagulant.

The lupus anticoagulant (LA) phenomenon created world-wide interest recently. Various tests have been devised to identify LA in plasma, but none of these methods have been universally accepted. In this study 16 cases labelled LA positive by a prior kaolin clotting time (KCT) test were reassessed by four other methods, namely delta KCT (delta kaolin clotting time), APTT (activated partial thromboplastin time), PNP (platelet neutralization procedure), and DRVVT (dilute Russell viper venom time). Anti-cardiolipin antibodies (ACL) were also looked for. In our hands the delta KCT proved to be a simple, sensitive test, not influenced by oral anticoagulant therapy, and we recommend it as a screening test. Where the presence of LA is strongly suspected on clinical and other groups, more than one method may be necessary for the diagnosis.

Autoantibodies↗