Pregnancy following percutaneous transluminal angioplasty.
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Biomedical subjects
Publications and source records attributed to S Gordon.
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Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors.
Stromal macrophages (M phi) have been localized in situ and isolated within erythroid clusters from human marrow. Stromal M phi arborize in an extensive network uniformly distributed throughout marrow interstitium, and express the phenotype CD4+, CD11a+, CD11c+, CD13+, CD14+, CD16+, CD18+, CD31+, CD32+, FcRI+, HLA-DR+, and CD35-, transferrin receptor-negative, and CD11b (weak). They express endocytic receptor antigens, but show significant differences in myeloid antigen expression compared with freshly harvested or cultured monocytes. Human stromal M phi are therefore specialized mature marrow M phi that are accessible for further investigations in infectious, storage, or hemopoietic disorders.
We reviewed the charts of 24 patients with malaria seen at the Queens Hospital Center, Jamaica, NY, over the past five years. Twenty-three patients were foreign citizens. Eighteen patients were infected with Plasmodium vivax and six with Plasmodium falciparum. Malaria was suspected on admission in 19 of the 23 hospitalized patients. Five patients were admitted with unrelated diagnoses, and four of these experienced diagnostic delay. All diagnoses were confirmed with thin blood smears. Twenty-one patients were febrile, and 18 patients had prominent gastrointestinal tract symptoms. Serum glucose level was increased in nine patients, and hypoglycemia occurred in one. Four patients also had intestinal parasites. Malaria should be suspected in travelers with gastrointestinal tract symptoms, and patients with malaria may have other parasitic infections. Most patients with P vivax infections can be treated as outpatients, since the course is usually uncomplicated.
Hemolytic uremic syndrome is a rare entity in patients with carcinoma and presents with a triad of renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia. We report this syndrome for the first time in a patient with small cell lung carcinoma. Spontaneous platelet aggregation of washed normal platelets was demonstrated using patient plasma. Circulating immune complex levels were not elevated. The entity completely resolved after treatment with plasma, vincristine, aspirin, and dipyridamole.
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Lysozyme is a major secretory product of human and rodent macrophages and a useful marker for myelomonocytic cells. Based on the known human lysozyme amino acid sequence, oligonucleotides were synthesized and used as probes to screen a phorbol 12-myristate 13-acetate-treated U937 cDNA library. A full-length human lysozyme cDNA clone, pHL-2, was obtained and characterized. Sequence analysis shows that human lysozyme, like chicken lysozyme, has an 18-amino-acid-long signal peptide, but unlike the chicken lysozyme cDNA, the human lysozyme cDNA has a greater than 1-kilobase-long 3' nontranslated sequence. Interestingly, within this 3' region, an inverted repeat of the Alu family of repetitive sequences was discovered. In RNA blot analyses, DNA probes prepared from pHL-2 can be used to detect lysozyme mRNA not only from human but also from mouse and rat. Moreover, by in situ hybridization, complementary RNA transcripts have been used as probes to detect lysozyme mRNA in mouse macrophages and Paneth cells. This human lysozyme cDNA clone is therefore likely to be a useful molecular probe for studying macrophage distribution and gene expression.
During mammalian development the fetal liver plays an important role in hematopoiesis. Studies with the macrophage (M phi)-specific mAb F4/80 have revealed an extensive network of M phi plasma membranes interspersed between developing erythroid cells in fetal liver. To investigate the interactions between erythroid cells and stromal M phi, we isolated hematopoietic cell clusters from embryonic day-14 murine fetal liver by collagenase digestion and adherence. Clusters of erythroid cells adhered to glass mainly via M phi, 94% of which bound 19 +/- 11 erythroblasts (Eb) per cell. Bound Eb proliferated vigorously on the surface of fetal liver M phi, with little evidence of ingestion. The M phi could be stripped of their associated Eb and the clusters then reconstituted by incubation with Eb in the presence of divalent cations. The interaction required less Ca++ than Mg++, 100 vs. 250 microM for half-maximal binding, and was mediated by a trypsin-sensitive hemagglutinin on the M phi surface. After trypsin treatment fetal liver M phi recovered the ability to bind Eb and this process could be selectively inhibited by cycloheximide. Inhibition tests showed that the Eb receptor differs from known M phi plasma membrane receptors and fetal liver M phi did not bind sheep erythrocytes, a ligand for a distinct M phi hemagglutinin. We propose that fetal liver M phi interact with developing erythroid cells by a novel nonphagocytic surface hemagglutinin which is specific for a ligand found on Eb and not on mature red cells.
Occult infection of the uterine cervix by human papillomavirus (HPV) is assumed when viral DNA sequences are detected from cervical swabs but no lesion is detectable and the Papanicolaou smear is negative. In an attempt to identify what histological changes correlate with occult infections, DNA was extracted from 200 cervical swabs taken from hysterectomy specimens. The DNA was analyzed by Southern blot hybridization for the presence of HPV sequences. Eleven cases (5.5%) were positive. The entire cervix from each case as well as from 28 negative cases was processed for histological analysis. One of the positive cases contained a CIN 2 lesion. The other 10 showed parakeratosis, papillomatosis, acanthosis, as well as focal nuclear pleomorphism and perinuclear halos (borderline koilocytotic atypia) in proportions equal to the negative controls. In situ hybridization analysis of the cases that showed borderline koilocytotic atypia were negative. These findings confirm that clinically and cytologically occult HPV infection of the uterine cervix is not associated with diagnostic histological changes. This underscores the need for caution when interpreting cervical biopsies that show changes suggestive, but not absolutely diagnostic, of HPV infection. Further, the precise epithelial location of the virus remains unclear.
The morphology of bipolar electrograms recorded in the right atrium was examined in nine patients in an attempt to discriminate retrograde from anterograde atrial signals to an extent that would be useful for physiologic pacing. Peak-to-peak amplitude, duration, square root of energy (energy), maximum slew rate, mean slew rate, and polarity were examined in the time domain. Maximum frequency, half-power frequency, Fourier amplitude peak, and frequency of peak were measured in the frequency domain. There was a significant difference between anterograde and retrograde signals for all variables related to amplitude; these variables are peak-to-peak amplitude, energy, Fourier amplitude peak, maximum slew rate and mean slew rate. In seven of nine patients there was at least one variable sufficiently discriminating to insure reliable detection of anterograde signals while systematically rejecting retrograde signals. However, no individual variable was able to effect this discrimination in more than four patients and at least three variables were needed for all seven patients: maximum frequency, one of either energy and Fourier amplitude peak, and one of either frequency of peak or half-power frequency (six possible combinations). Thus, although differences between anterograde and retrograde atrial activity can be demonstrated in most patients, no single parameter displays sufficient discriminating power to facilitate physiologic pacing in patients exhibiting retrograde activity.
Plasma membrane receptors control macrophage activities such as growth, differentiation and activation, migration, recognition, endocytosis and secretion. They are therefore important in a wide range of physiological and pathological processes including host defence, inflammation and repair, involving all systems of the body including the arterial wall and nervous system. The versatile responsiveness of these cells to various stimuli depends on their ability to express a large repertoire of receptors, some restricted to macrophages and closely related cells, others common to many cell types. This volume contains reviews of the macrophage receptors that are best characterized and deals with aspects of signal transduction and function of the actin cytoskeleton. Our introduction is designed to place these topics in perspective. We summarize features of constitutive and induced mononuclear phagocyte distribution within the body and consider receptor expression and macrophage responses in the context of cell heterogeneity associated with its complex life history. We classify receptors discussed in detail in other chapters, list ligand-binding properties that are not as well defined, and briefly review general features of receptor function in macrophages. An understanding of macrophage receptor biology should bring insights into the contribution of these cells to physiology and disease and result in an improved ability to manipulate activities within the mononuclear phagocyte system.
Immunocytochemical staining of tissues with the mouse macrophage-specific monoclonal antibody, F4/80, has shown that large numbers of stromal macrophages are present in adult and foetal haematopoietic tissues. Macrophage plasma membrane processes are seen to establish extensive associations with myeloid and erythroid cells in adult bone marrow and with developing erythroblasts in foetal liver, suggestive of local trophic interactions. To explore the nature of these interactions, methods were developed for isolation of resident bone marrow macrophages (RBMM) and foetal liver macrophages (FLM). Following collagenase digestion of bone marrow or foetal liver, clusters were obtained which were composed of one or more central macrophages surrounded by proliferating haematopoietic cells. After attachment of clusters to glass coverslips, adherent macrophages could be stripped free of haematopoietic cells by pipetting in the absence of divalent cations. The purified RBMM, but not FLM, expressed a novel haemagglutinin, which mediated binding, without ingestion, of large numbers of unopsonized sheep erythrocytes by a divalent cation-independent mechanism. In view of the possibility that this sheep erythrocyte receptor (SER) could interact with a homologous ligand on mouse bone marrow cells, its properties were examined. SER was found to be a lectin-like protein which recognized protease-resistant sialylated glycoconjugates on sheep erythrocytes. The expression of SER was restricted to certain stromal tissue macrophages and was low or absent on monocytes and macrophages obtained from serous cavities. High levels of SER could be induced on elicited peritoneal macrophages by cultivation in mouse serum and the induced receptor was found to mediate low-avidity binding of murine bone marrow cells with characteristics indistinguishable from those seen for binding of sheep erythrocytes. However, maximal binding of bone marrow cells to RBMM depended on a distinct, divalent cation-dependent adhesion system. Using erythroblasts as a ligand, FLM were selected to explore the properties and expression of this adhesion receptor, the erythroblast receptor (EbR). Similar to SER, EbR did not mediate ingestion, and was restricted in its expression to foetal and adult stromal tissue macrophages. Unlike SER, EbR activity was not affected by neuraminidase treatment of the ligand and the receptor was not induced on peritoneal macrophages cultured in mouse serum. EbR appears to be a novel cell adhesion receptor because it was unaffected by inhibitors of several previously described cell adhesion molecules, including the fibronectin receptor. Future studies will attempt to explore the f
A leukoerythroblastic blood picture and tear drop shaped red cells are two characteristic features of myelofibrosis (MF). Following our earlier observation of an increase in the hemoglobin level with chemotherapy, we have now reviewed the pre- and post-treatment peripheral blood smears from 14 patients with MF to assess the effect of treatment on the above mentioned peripheral blood features. Our results suggest that these features are reversible with effective chemotherapy.
The mechanisms which generate heterogeneity amongst resident tissue macrophages (M phi) are poorly understood. In a previous study we described a novel mouse M phi haemagglutinin, which binds unopsonized sheep erythrocytes. This sheep erythrocyte receptor (SER) is expressed at high levels on stromal M phi from bone marrow and lymph nodes, but at low levels on M phi from serous cavities and broncho-alveolar spaces. In this paper we demonstrate that a species-restricted factor in mouse serum is required in vitro for optimal maintenance of SER on resident bone marrow M phi and for its induction on M phi populations which normally lack this receptor. Using thioglycollate-elicited peritoneal M phi, induction of SER by mouse serum was dose-dependent, reached maximal levels by 3-4 days, required the continuous presence of mouse serum, and was fully reversible. Re-expression following trypsinization was inhibited by cycloheximide, showing that protein synthesis by M phi was necessary. Using a quantitative microtitre plate assay to measure levels of the inducing activity (SER-IA) in different samples, it was found to be heat-labile, non-dialysable, precipitable by polyethylene glycol and inactivated at pH 4 but not at pH 9.6. On gel filtration of mouse serum, a single major peak of activity was obtained with an apparent MW of around 70,000. SER-IA appears to be unrelated to a variety of factors and cytokines which affect M phi function, including colony-stimulating factor-1 (CSF-1). The possible role of SER-IA in regulating the differential expression of SER in vivo is discussed.
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The Normative Model for Decision Styles in Coaching (Chelladurai and Haggerty, 1978) was empirically tested using Canadian Intercollegiate (CIAU) soccer teams. The subsequent utility of the model's prescriptions for optimizing decision styles of soccer coaches was seriously questioned. Only 33% agreement was found with the model's prescriptions for both CIAU coaches and their athletes. Neither coaches nor athletes were particularly inclined to use delegation in decision making. Athletes, more than their coaches, preferred consultative styles. In support of research findings from business and industrial settings, there was evidence to suggest that high congruence scores between a coach's decision styles and those preferred and perceived by athletes, could predict athlete perceptions of coaching effectiveness.
Macrophage interactions with extracellular matrix and other cells are important in phagocytosis, inflammation, and immunity. To learn more about the surface molecules involved in adhesion we compared the binding of murine macrophages and polymorphonuclear leukocytes (PMN) with artificial substrate in vitro. A distinctive type of adhesion of thioglycollate-elicited peritoneal macrophages (TPM) to bacteriologic plastic (BP) was defined, which was pronase-sensitive, Mg2+-dependent, and required cytoskeletal stabilization. A rat mAb designated 5C6 was isolated because it inhibited TPM attachment to BP, as well as mediating detachment of TPM adherent to that substratum. In addition, it inhibited the attachment of PMN to tissue culture plastic. This antiadhesive property of 5C6 mAb required intact IgG; the F(ab')2 fragment was partially effective and Fab was ineffective. 5C6 recognized the type 3 complement receptor, inhibiting rosetting of EAC3bi to TPM and immunoprecipitating a heterodimer of 160 and 95 kD that comigrated with the M1/70 immunoprecipitate. 5C6 recognized a pronase-stable epitope distinct from that of M1/70. Other mAbs, including M1/70 (CR3) and 2.4G2 (FcR), failed to have any antiadhesive effect in vitro. The inhibitory activity of 5C6 in short-term adhesion assays correlated with its inhibition of recruitment of myelomonocytic cells to a thioglycollate-elicited peritoneal exudate in vivo, after intravenous injection of mAb. 5C6 IgG inhibited recruitment of myelomonocytic cells by 84 +/- 3% at 1 d compared with saline-injected controls. The F(ab')2 fragment and a class-matched control IgG had little effect. Recruitment of TPM at 4 d was also efficiently inhibited by 5C6 IgG. 5C6 IgG was not cytotoxic, had no effect on marrow egress, did not cause increased phagocytic clearance of circulating neutrophils, and had no adverse effect on chemotaxis in vitro. We show that CR3 alone of the LFA-family is necessary for the recruitment of myelomonocytic cells to inflammatory stimuli such as thioglycollate broth. This strategy may be of general use in isolating reagents that inhibit the adhesive function of CR3 and provides a novel approach to antiinflammatory therapy.
Mononuclear phagocytes which express the HIV entry receptor CD4 have been implicated as possible sites of virus replication in brain, but there is still considerable uncertainty as to which cells in the CNS express CD4 Ag. Although it is not susceptible to HIV infection the rat provides a model to define expression of the CD4 Ag on MO in brain. We report that the CD4 epitopes W3/25 and OX35 are found only on monocytes, MO, microglia, and occasional lymphocytes and not on neurons, other glia, or endothelium. CD4 Ag levels are modulated during microglial differentiation, after reactivation after local inflammation, and within the intact blood brain barrier. MO and microglia also express other potential plasma membrane binding and entry sites for HIV viz Fc and complement receptors that are regulated independently of CD4.