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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 433 records · Page 24Linked to original sources

Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain.

Macrophages and microglia in the developing and adult mouse brain have been identified by immunohistochemical localization of the macrophage-specific antigen F4/80 and monoclonal antibodies to the FcIgG1/2b (2.4G2) and type-three complement (Mac-1) receptors. In the adult mouse there are two classes of F4/80-positive cells; those associated with the choroid plexus, ventricles and leptomeninges and the microglia. The cells bearing Fc and complement receptors are indistinguishable, by their morphology and distribution, from those revealed by F4/80. During development macrophages invade the brain and can be followed through a series of transitional forms as they differentiate to become microglia. Macrophage invasion occurs when naturally dying cells are observed in large numbers and this is consistent with the idea that dying neurons and axons provide a stimulus for macrophage infiltration. Our results provide strong support for the hypothesis that the microglia are derived from monocytes and show that microglia possess receptors which would allow them to play a part in the immune defence of the nervous system.

Animals↗

Myelodysplasia in cadaver renal allografts: a report of four cases.

A report of four cases of severe myelodysplastic syndromes (MDS) culminating in death in cadaver renal recipients is presented. All patients received predominantly antimetabolite immunosuppressive therapy. Abnormal cytogenetics were found in two cases. Survival was brief in all cases from the time of diagnosis. These cases add to the increasing number of patients treated with antimetabolite drugs for nonmalignant conditions who develop severe hematological abnormalities which might be a prodrome of acute nonlymphocytic leukemia.

Adult↗

Sequence of mechanical, electrocardiographic and clinical effects of repeated coronary artery occlusion in human beings: echocardiographic observations during coronary angioplasty.

The direct manipulation of coronary blood flow to induce regional myocardial ischemia has been almost entirely limited to experimental animal models. Thus, the detection of ischemia-induced left ventricular dysfunction in human subjects has been generally limited to observations made under conditions of diagnostic loading or during spontaneous clinical events. Percutaneous coronary angioplasty requires repeated interruptions of coronary blood flow for periods as long as 1 minute. The resulting appearance of or increase in ischemia-produced changes in myocardial function were detected by two-dimensional echocardiography in 18 patients undergoing angioplasty of 22 coronary stenoses. Accordingly, left ventricular contraction was studied during 52 episodes of regional coronary blood flow interruption and reperfusion in the process of inflating and deflating the angioplasty balloon. Before angioplasty, left ventricular wall motion was normal in 14 patients. There was mild anteroapical hypokinesia in two patients, anteroapical akinesia in one and mild inferior hypokinesia in one. Balloon inflations repeatedly produced new or increased wall motion abnormalities in the distribution of the instrumented coronary artery in 19 (86.4%) of the 22 procedures, but did not alter wall motion during angioplasty of one left circumflex artery lesion, one highly collateralized left anterior descending artery stenosis and one left anterior descending stenosis that had already caused severe anteroapical dyssynergy. Hypokinesia, usually rapidly progressing to dyskinesia, began 19 +/- 8 seconds (mean +/- SD) after coronary occlusion. Wall motion began to normalize 17 +/- 8 seconds after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sequelae of left ventricular electrical endocardial ablation.

The endomyocardial residual effects of left ventricular endocardial electrical ablation utilizing unipolar and bipolar electrode catheters were studied in 15 dogs. Histopathologic techniques specific for contraction band necrosis revealed that the mean maximal depth and breadth of necrosis was 0.63 +/- 0.44 and 1.23 +/- 0.82 cm, respectively. The dimensions of necrosis were significantly increased when utilizing larger energy discharges, especially through unipolar electrodes. Four dogs died during the procedure, three from ventricular fibrillation and one from asystole, and two died suddenly within the succeeding 24 hours. Endocardial thrombi were noted at necropsy in two dogs. In conclusion, transcatheter endocardial electrical ablation may destroy a sufficient mass of myocardium to interrupt arrhythmogenic conduction tissue, especially when larger currents are delivered through unipolar electrodes. However, serious ventricular arrhythmias and endocardial thrombi should be anticipated.

Animals↗

Enlargement of the right heart in the endurance athlete: a two-dimensional echocardiographic study.

M-mode echocardiographic studies of endurance-trained athletes have provided conflicting data for right ventricular (RV) dimensions and no data for right atrial (RA) size. Since two-dimensional echocardiography provides a more accurate measurement of the RV and RA, it was employed together with M-mode echocardiography to evaluate 12 male endurance athletes and 12 sedentary controls matched for body size and age. All subjects were screened by history, physical examination, ECG, and maximal exercise testing. RV and RA areas were planimetered in the apical four-chamber view while displaying maximal chamber sizes. Athletes had significantly greater left ventricular (LV) wall thickness (P less than 0.01), LV area (P less than 0.001), and left atrial (LA) area (P less than 0.01). They also had greater RV area (P less than 0.01), RV wall thickness (P less than or equal to 0.05), and RA area (P less than or equal to 0.01). Maintained proportionality of the cardiac chamber dimensions in the athletes was shown by similar ratios of right-to-left ventricular areas, right-to-left atrial areas, and right-to-left ventricular wall thicknesses in both groups. The symmetry of the greater athlete's heart differs from most pathological conditions which have heterogeneous effects on specific cardiac chambers.

Adult↗

24-hour ambulatory manometry in diagnosis of esophageal motor disorders causing chest pain.

The clinical diagnosis of motor disorders of the esophagus leading to chest pain usually lacks documentation by manometry despite the use of sophisticated equipment as well as pharmacologic manipulation. We have developed an ambulatory manometry system that allows us to monitor motility in the esophagus on an outpatient basis for 24 hours. This method seems well tolerated, and tracings obtained are of excellent quality, allowing careful inspection and evaluation of details. Simultaneous 24-hour esophageal pH and surface ECG recordings were also obtained. We believe the technique, when perfected, will significantly enhance the understanding and documentation of the cause of chest pain in patients with motor dysfunction of the esophagus.

Ambulatory Care↗

Intrinsic coagulation pathway in end-stage renal disease associated with spinal cord injury treated with hemodialysis.

Plasma procoagulant activities of factors XII, XI, IX, and VIII and plasma concentrations of factor XII antigen and high molecular weight kininogen (HMK) were determined in nine men with chronic renal failure (CRF) associated with long-standing spinal cord injury (SCI) treated with hemodialysis. The results were compared with those obtained in a group of 10 ambulatory CRF patients and 8 normal volunteers (control group). Congenitally deficient plasmas were used as the substrate for the measurement of procoagulant activities in a one-stage clotting assay. Monospecific antibodies were employed in the measurement of factor XII antigen and HMK using gradient plate immunodiffusion and rocket immunoelectrophoresis. Factor XII coagulant activity and antigen concentration were significantly increased in the SCI group. The mean values for plasma factor XI and IX activities in the SCI group were comparable with those observed in the ambulatory patients and normal control group. However, marked variations in factor XI and IX levels were noted among the SCI patients with a few instances of mild to moderate factor deficiencies and several cases of markedly elevated levels. Factor VIII activity was markedly increased, with only two of the nine patients exhibiting normal values. HMK concentration in the SCI group was comparable with values obtained for the other groups. Following dialysis, factor XII antigen concentration rose and factor XI activity fell slightly but significantly. The results indicate that the combination of CRF and long-standing SCI is associated with marked aberrations of intrinsic coagulation pathway. The underlying mechanisms and the clinical consequences of these abnormalities are not known and require further investigation.

Adult↗

Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone.

We describe a sensitive assay to measure immune activation of human macrophages in cell culture. Freshly isolated blood monocytes from normal subjects lack the ability to endocytose and degrade mannosyl-terminated glycoconjugates via specific receptors, but acquired this activity after cultivation in autologous serum for approximately 3 d. Addition of specific antigen, purified protein derivative, or T cell mitogens to mononuclear cells prevented the appearance of macrophage mannosyl receptor activity and lymphokine, gamma-, and alpha-interferons selectively down-regulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and gamma-interferon on mannosyl receptors can be prevented by 10(-8) M dexamethasone. Dexamethasone also inhibited release of another macrophage activation marker, plasminogen activator, which was increased by both gamma- and alpha-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids.

Adult↗

Interaction of human monocytes, macrophages, and polymorphonuclear leukocytes with zymosan in vitro. Role of type 3 complement receptors and macrophage-derived complement.

Macrophages take up zymosan in the absence of exogenous complement via receptors for iC3b (type 3 complement receptors) acting with or without lectin-like receptors for mannosyl-fucosyl-terminated glycoconjugates. We previously provided evidence that macrophages themselves secrete complement-alternative pathway components able to opsonize zymosan locally (Ezekowitz et al., J. Exp. Med. 1984. 159:244-260). We show here that covalently bound C3 cleavage products C3b and iC3b can be eluted from zymosan particles cultivated with 36-h adherent human monocytes in the absence of serum. The ligand binding site of type 3 complement receptors is involved in macrophage-zymosan interactions as shown by inhibition studies of zymosan binding and uptake with Fab fragments of anti-C3 antibodies and monoclonal antireceptor antibodies M01 and OKM10. In contrast, antibody IB4, which binds to a receptor epitope distinct from the binding site, does not inhibit zymosan uptake. Selective modulation of macrophage receptors onto anticomplement receptor antibody and mannose-rich yeast mannan, respectively, confirms that the complement and lectin-like receptors are distinct. Human polymorphonuclear leukocytes, which express receptors for complement, but are not known to secrete complement proteins, bind and ingest only exogenously opsonized zymosan. Unopsonized zymosan is a poor trigger of respiratory burst activity in neutrophils or 7-d adherent human macrophages, but induces cell aggregation and secretion of large amounts of superoxide anion when these cells are co-cultivated in serum-free medium and challenged with zymosan. Our studies indicate that complement and/or other products synthesized by macrophages at extravascular sites could play an important role in opsonization and lysis of pathogens able to activate the alternative pathway and mediate macrophage-neutrophil collaboration in first-line host defence.

Animals↗

Intracellular antigens associated with the cytoplasmic surface of phagolysosomes.

Monoclonal antibodies were prepared to study the cytoplasmic face of latex phagolysosomes isolated from thioglycollate-elicited mouse peritoneal macrophages. Phagolysosomes obtained by sucrose flotation contained latent beta-glucuronidase activity and tightly associated cellular proteins and glycoproteins. Fluorescence-activated cell sorter analysis, scanning and transmission electron microscopy showed that the particle preparation contained greater than 98% monomers and dimers, invested with a smooth layer of membrane and minimally contaminated with cytoplasmic adhesions. Sera for immunized rats bound preferentially to isolated phagolysosomes rather than intact cells and monoclonal antibodies PL-1 and PL-4 were isolated on this basis. Indirect fluorescent, radio- and peroxidase immunobinding assays with intact and methanol-permeabilized cells confirmed that antigens PL-1 and PL-4 were exclusively intracellular and that well-washed phagolysosomes bound both antibodies. These antigens were found in a variety of cells from several species and in macrophages not fed latex. Although the PL-1 antigen could not be immunoprecipitated, intracellular staining was characteristic of intermediate filament distribution, that is, it was in the form of a fine intersecting network, which collapsed, reversibly, in a rim round the nucleus upon treatment with colcemid. The staining pattern was undetectable in cells 1 h after adherence to a substratum, but gradually appeared after 6-12 h. The PL-4 antibody has been shown elsewhere to define a Ca2+-binding protein of approximately 20 000 molecular weight, which is phosphorylated during phagocytosis. This antibody stained stress fibres and revealed a widespread punctate distribution of antigen within cells at all stages after adhesion. The nature of the association between these intracellular antigens and phagolysosomes and their possible role in phagocytosis are not known.

Animals↗

A new synthetic monofilament absorbable suture made from polytrimethylene carbonate.

The physical and biologic characteristics of a new synthetic absorbable monofilament suture, glycolide trimethylene carbonate (GTMC) are presented. The suture was formulated to combine predictable in vivo performance of synthetic absorbable sutures with the handling characteristics of a monofilament suture. Three in vivo studies were described: strength, gross and microscopic absorption and reaction, and radiolabelled decay. The studies carried out in rats showed cumulative strength retention of sizes 0, 00, 4-0 and 5-0 of 81 per cent at 14 days, 59 per cent at 28 days and 30 per cent at 42 days. Strength retention was consistent throughout the size spectrum. Absorption of sizes 00 and 4-0 were studied in subcutaneous implantations in rabbits. Histologic assessment of absorption obtained from serial sections at intervals of three to nine months showed that, in both sizes, complete absorption occurred between six and seven months. At six months, 83 per cent of size 00 was absorbed and size 4-0 was 93 per cent absorbed. At seven months, no implanted material was discernible histologically. Untoward tissue reactions, such as acute inflammatory cells, abscesses or tissue necrosis, were not observed. There were no signs of cellular mobilization of any kind observed remote from the implant. Absorption of GTMC sutures was achieved through the action of mononuclear and multinuclear macrophages which were confined to the implant and sequestered by a fibrous connective tissue capsule. When implant absorption was complete, resorbtion of the macrophage component was observed which was replaced by a narrow cord of fibrous tissue and collagen. The results of studies of radiolabelled sutures carried out in the subcutaneous tissues of rats revealed urine and expired CO2 to be the major excretary routes of the metabolites. By 22 to 24 weeks, 0.1 to 0.7 per cent of the total implanted radioactivity remained at the suture sites. Tissue deposition and excretion of radioactivity suggests similar metabolism of the sutures in both species. We conclude that GTMC sutures maintain good strength with little or no absorption during the critical wound healing period, absorbs completely from tissues in six to seven months with minimal tissue reaction and, therefore, provides an absorbable, flexible, monofilament material with extended support that is strong and effective.

Absorption↗

Antithrombin deficiency in end-stage renal disease associated with paraplegia: effect of hemodialysis.

Plasma antithrombin III activity and concentration were determined in nine men with end-stage renal disease (ESRD) associated with spinal cord injury (SCI). To determine the possible effects of hemodialysis measurements were repeated following dialysis. Values obtained in the SCI-ESRD group were compared with those obtained in a group of healthy volunteers and a group of 10 ambulatory men with ESRD. A normal pooled plasma was used as the internal standard for all assays. While antithrombin deficiency was observed in both uremic groups it was most severe in the group with SCI. Results demonstrated the association of antithrombin deficiency with ESRD and its potentiation in the presence of SCI. The mechanisms by which SCI compounds the uremia-induced antithrombin deficiency were not known. A mild increase in antithrombin level was noted following dialysis and was thought to be in part due to fluid removal by dialysis.

Adult↗

Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients.

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adaptive device for the quadriplegic golfer.

Participation in sports by the individual having quadriplegia is often limited because of the loss of use of intrinsic and extrinsic muscles of the hand. An adaptive device has been developed to enable quadriplegic patients to participate in a golf program. It consists of a molded forearm cuff of Kydex thermoplastic, to which a golf club is attached by several clamps and a golf glove altered by sewing velcro pile to the tips of all fingers and to the back of the glove. These have provided stability to the golfer's grip of the club, and have made it possible for quadriplegic patients to play successfully on the Par 3 golf course at the Medical Center.

Forearm↗

The influence of infarction site and size on the ventricular response to coronary thrombolysis.

To test the hypothesis that myocardial infarction (MI) size rather than location determines the ventricular response to reperfusion, we studied 69 patients receiving intracoronary streptokinase within five hours of chest pain onset who displayed sustained reperfusion at 8.4 +/- 3.4 (SD) days. Twenty reperfusion failures served as controls. There were 31 patients with anterior MIs, 18 of which were estimated to be large based on an ejection fraction (EF) at reperfusion of less than 50%; 14 of 38 patients with inferior MIs also had large MIs. The EF increased at follow-up by 6.4% +/- 2.6% in patients with large anterior MIs and by 8.2% +/- 2.5% in those with large inferior MIs; in contrast, it increased by only 1.8% +/- 2.6% in patients with small anterior MIs and significantly decreased by 5.8% +/- 1.9% in patients with small inferior MIs. Six controls with large MIs (four anterior) displayed no change in EF; in 14 with small MIs (ten inferior), it fell slightly. There were no significant group differences in the number of diseased vessels, residual stenosis, or collaterals. It is concluded that MI size, not site, largely determines the ventricular functional response to early reperfusion; thus, patients with inferior MIs cannot be disqualified on this basis alone for thrombolytic therapy.

Coronary Disease↗

Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan.

We have examined the role of macrophage (M phi plasma membrane receptors for the cleaved third complement component (iC3b; CR3) and mannosyl, fucosyl terminated glycoproteins (MFR) in uptake of unopsonized zymosan. Monoclonal antibodies against CR3, M1/70 (Mac-1) and MO1, each inhibited approximately 50% of uptake of 125I-zymosan by murine and human M phi, respectively. Yeast mannan inhibited 0-50% of zymosan uptake in various M phi, in parallel with their expression of MFR. We demonstrated that M phi were the source of C3 in our assay and that the activity of other components of the complement system, namely a C3 convertase, factor I, and a factor I cofactor were also present in serum-free cultures of human monocytes. Macrophage C3 was deposited rapidly, within 10 min, on the zymosan particles and mediated binding, ingestion, and stimulation of superoxide release in BCG-activated and thioglycollate-elicited peritoneal M phi via CR3. Local secretion of complement proteins by M phi themselves can therefore opsonize pathogens and cells able to activate the alternative pathway and effect their destruction.

Animals↗

The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia.

The tissue distribution of the murine macrophage-specific antigen F4/80 has been analysed using an immunohistochemical technique. The antigen is observed on all known macrophage populations (including Kupffer cells and bronchoalveolar macrophages) and is absent from any cell types that are definitely not mononuclear phagocytes. Microglial cells from brain express F4/80. F4/80+ macrophages observed associated with epithelia can be divided into two categories, intraepithelial and periepithelial. The former includes epidermal Langerhans cells and cells with similar morphology in other stratified squamous epithelia (cervix, oesophagus), pseudostratified epithelium (trachea), transitional epithelium of urinary bladder, and simple epithelia lining various ducts (salivary gland, common bile duct, tracheobronchial gland). Periepithelial F4/80+ cells, apparently spread immediately below the basal lamina, are associated with simple epithelia throughout the gastrointestinal, respiratory, and male and female reproductive tract as well as the brain ependyma. A major class of periepithelial F4/80+ cells is associated with capillaries throughout the microcirulation. The role of these macrophage populations in control of epithelial function is discussed.

Animals↗