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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 415 records · Page 23Linked to original sources

Surface-associated vesicles in retinal arterioles and venules.

The surface-associated vesicles in retinal arterioles and venules were studied after fixation in glutaraldehyde-tannic acid or after intravitreal injection of peroxidase or lactoperoxidase. The vesicles were concentrated along the abluminal (basal) surface of the endothelial cells and along the plasma membranes of smooth muscle cells in arterioles and of pericytes in post-capillary venules. They were rarely encountered in the deeper regions of these cells. In perpendicular sections through the cell surface the majority of vesicles were in continuity with the plasma membrane whereas in tangential sections, they appeared to lie "free" in the cytoplasm. All such vesicles were labeled after exposure to tannic acid or to the heme-proteins. Peroxidase-reaction product was never seen in the lumen of the vessels. These observations suggest that the surface vesicles in endothelial cells, smooth muscle cells and pericytes are invaginations of the plasma membrane and are thus not involved in the transcytosis or endocytosis of proteins. The vesicles in the latter two cell types may be involved in some aspect of contractility rather than pinocytosis.

Animals↗

Attenuation of exercise training effects in patients taking beta blockers during early cardiac rehabilitation.

Cardiorespiratory responses to graded treadmill tests administered 1 month after myocardial infarction or coronary bypass surgery and again after 4 weeks of aerobic training were compared in 24 patients taking beta blockers and 15 control patients. There were no significant differences before training between the groups in age, weight, ventricular ejection fraction, oxygen uptake (Vo2) during the fixed work load (1.7 mph/10% grade), Vo2 at the ventilatory threshold, or Vo2max. After training, Vo2max was significantly increased (p less than 0.05) by 16% in the beta-blocker group and by 21% in controls. However, the group taking beta blockers showed no significant change in oxygen pulse (Vo2/heart rate) at the fixed work load or at the ventilatory threshold, whereas the controls increased Vo2/heart rate at the fixed work load by 9% (p less than 0.05) and at the ventilatory threshold by 22% (p less than 0.05). Metabolic and ventilatory responses to submaximal exercise should therefore also be considered when evaluating the efficacy of exercise training in patients taking beta blockers.

Adrenergic beta-Antagonists↗

The effect of modified transurethral sphincterotomy on autonomic dysreflexia.

Autonomic dysreflexia continues to be a major problem in spinal cord injury patients. In our report 16 patients with spinal cord lesions above the T6 level and a history of autonomic dysreflexia also had detrusor-sphincter dyssynergia. Of these patients 12 (75 per cent) had evidence of dysreflexia during cystometry. In addition, the dysreflexic response in blood pressure was shown to correlate with the high intravesical and urethral pressures measured during cystometry. Modified transurethral sphincterotomies subsequently were performed on all patients as recommended therapy for detrusor-sphincter dyssynergia. Repeat cystometry revealed significant decreases in intravesical and urethral pressures compared to before sphincterotomy (p less than 0.001) along with an associated significant decrease in blood pressure (p less than 0.01). Other dysreflexic responses also were markedly attenuated. These results suggest an association among detrusor-sphincter dyssynergia, high intravesical and urethral pressures, and autonomic dysreflexia. Our data indicate further that the frequency and magnitude of autonomic dysreflexia can be diminished significantly by modified external sphincterotomy.

Adult↗

Accuracy of computerized electrocardiographic identification of left ventricular hypertrophy as determined by echocardiographic measurements of left ventricular mass: evaluation of a widely used computer program.

The Hewlett-Packard 1000 electrocardiographic management system employs a user-interactive computer with revisable software. The diagnostic accuracy of this system in predicting left ventricular hypertrophy has been evaluated by comparing computer-predicted with anatomic left ventricular hypertrophy. The latter was defined as a left ventricular mass greater than 247 g as determined by M-mode echocardiography within 1 week of the computerized electrocardiogram. In this study, the Hewlett-Packard system was evaluated in 134 consecutive patients having anatomic left ventricular hypertrophy and 157 similarly studied patients with a normal left ventricular mass. By means of various combinations of voltage criteria, ST-T wave changes, abnormal QRS duration or ventricular activation time, left atrial enlargement and left axis deviation, the computer correctly identified 43 of 134 patients with left ventricular hypertrophy (sensitivity 32%); left ventricular hypertrophy was suggested or identified in an additional 18 patients with a normal left ventricular mass (specificity 89%). Graded probability statements (that is, the "strength" of the left ventricular hypertrophy diagnosis) increased with ventricular mass not only in patients with anatomic left ventricular hypertrophy but also in the patients with a "false positive" computerized electrocardiogram. Overall diagnostic accuracy was improved only in men by adjusting the definition of left ventricular hypertrophy for sex (at least 300 g for men and 220 g for women). Diagnostic accuracy was significantly better in patients 65 years of age and younger than in older patients (p = 0.007). It is concluded that the overall performance of this computer program (version ECLSB6) requires modification to improve its accuracy in identifying left ventricular hypertrophy.

Age Factors↗

Extrinsic and common coagulation pathways in end-stage renal disease associated with spinal cord injury.

Data on the effects of combined long-standing spinal cord injury (SCI) and end-stage renal disease (ESRD) on blood coagulation system are limited. We studied the extrinsic and common pathways of blood coagulation system in 9 men with SCI-ESRD treated with maintenance hemodialysis. Plasma procoagulant activities of factors (F)VII, X and II were measured in a clotting assay using appropriate deficient plasmas as substrate. In addition, the antigen concentration of FII was measured using monospecific antibodies against human FII raised in goat in a gradient plate immunodiffusion system. Also measured were plasma fibrinogen concentration and platelet count. The results were compared with those obtained in a group of 10 ambulatory ESRD patients and 8 normal control volunteers. Plasma coagulant activity of FVII was markedly elevated and plasma fibrinogen concentration was moderately increased in SCI-ESRD patients. In contrast, plasma FII was mildly depressed while platelet count was within normal limits in SCI-ESRD patients. The data indicate that the combination of SCI and ESRD can lead to the alteration of the extrinsic and common coagulation pathways. Further studies are needed to elucidate the precise mechanism and the clinical significance of the observed abnormalities.

Adult↗

Monoclonal antibodies to a particulate superoxide-forming system stimulate a respiratory burst in intact guinea pig neutrophils.

Monoclonal rat antibodies were produced against a subcellular preparation of phorbol 12-myristate 13-acetate (PMA)-stimulated guinea pig neutrophils that retains NADPH-oxidase activity. Two antibodies, 1A10.4 and IG4, were isolated that bind to a surface antigen restricted to guinea pig neutrophils from bone marrow and peritoneal exudate and to macrophages and that trigger a respiratory burst in neutrophils in the presence of cytochalasin B. Intact antibody 1A10.4, subclass IgG2c, can trigger superoxide anion release directly; F(ab')2 fragments of 1A10.4 and intact IG4 require further cross-linking by F(ab')2 fragments of anti-rat immunoglobulin antibody. Both antibodies recognize the same antigen, a proteolipid of apparent molecular mass 10 kDa. Immunoprecipitation of solubilized oxidase activity with 1A10.4 brings down this activity as part of a macromolecular complex. Surface expression of the antigen is increased on treatment of cells with both PMA and cytochalasin B. 1A10.4 also triggers release of the granule enzyme beta-glucuronidase. Triggering of a respiratory burst by the antibodies appears distinct from the PMA and fMet-Leu-Phe signalling systems. These studies indicate that the antigen defined by antibodies 1A10.4 and IG4 becomes associated with the superoxide anion-generating system of neutrophils but may play a more general role in signal transduction in phagocytic cells.

Animals↗

Hyperamylasaemia and acute pancreatitis following endoscopic retrograde cholangiopancreatography.

Hyperamylasaemia and acute pancreatitis are the more common complications of endoscopic retrograde cholangiopancreatography (ERCP). Ninety patients who underwent ERCP +/- endoscopic papillotomy were monitored for rises in the serum amylase and the development of acute pancreatitis. The incidence of hyperamylasaemia (greater than 300 IU/L) was significantly greater (p = 0.01) when the pancreatic duct was imaged (75%) than with bile duct imaging alone (33%). The incidence of acute pancreatitis following imaging of the pancreatic duct +/- bile duct was 11.3% and was found to be significantly increased in those patients (n = 9) who also underwent endoscopic papillotomy. Imaging of the biliary tree only +/- endoscopic papillotomy carried no significant risk of acute pancreatitis. In those patients who developed pancreatitis, the rise in serum amylase occurred early and was significantly higher at 2 h following ERCP. These findings may help to identify patients who are at risk of developing this complication.

Acute Disease↗

Twelve years of clinical experience with lithium pulse generators.

The clinical performance of 9,651 lithium pulse generators, which were implanted at our registry hospitals since 1973, was assessed by analysis of actuarial survival data and information obtained at the time of pacemaker failure. Cumulative survival estimates for all units were: 5 years, 94 percent, 7 years, 81 percent, 10 years, 62 percent. Discriminant actuarial analysis revealed no differences between lithium iodine and lithium cupric sulfide longevity. Battery depletion was found in 49.1 percent of 277 units subjected to detailed explant analysis, while 31 percent and 8.7 percent had component and hermetic seal defects, respectively. Of the pulse generators with battery depletion, all but two units exhibited normal end-of-battery life behavior. We conclude that the lithium iodine and lithium cupric sulfide batteries are safe, long-term energy sources; however, the impact of reduced battery size and dual chamber pacing on these performance parameters is unknown.

Electronics, Medical↗

Interaction of West Nile virus with primary murine macrophages: role of cell activation and receptors for antibody and complement.

We have measured growth of West Nile virus in mouse primary peritoneal macrophages (resident, thioglycolate elicited, and Mycobacterium bovis BCG activated) and in macrophagelike (P338D1) and nonmacrophage (L929, PS clone D) cell lines infected in the absence or presence of specific antibodies (immunoglobulin G ([IgG], IgM), and complement. Monoclonal antibodies directed against Fc receptors (IgG1/2b, 2.4G2) and type 3 complement receptors (Mac-1) were used to define the role of each receptor. Virus yield depended on a balance between enhancement and neutralization and was influenced by the physiologic state of the macrophage, the receptor pathway of viral entry, the mouse strain and age of donor. BCG-activated macrophages displayed a greater ability to restrict West Nile virus than nonactivated cells only in the presence of antiviral IgM, with or without complement; the Fc receptors for various classes of IgG mediated striking enhancement. These studies identify some of the complex innate and acquired factors that determine the interaction between West Nile virus and primary macrophages in vitro.

Age Factors↗

Martial arts for the quadriplegic.

A program has been developed for teaching of martial arts to the spinal cord injured. Despite the great challenges, quadriplegic patients have been able not only to participate along with paraplegics, but have helped to develop innovative methods to modify techniques to their abilities. The benefits of the program are described.

Exercise Therapy↗

Hemorrhage vs rethrombosis after thrombolysis for acute myocardial infarction.

To determine whether or not the timing of heparin infusion affects either bleeding or reocclusion following intracoronary streptokinase for acute myocardial infarction, heparin was infused immediately after streptokinase in 89 patients and was delayed for 12 hours in the subsequent 93. Bleeding occurred in 22 immediate-heparin patients and was major in five (one fatal); there were 14 hemorrhages in the delayed-heparin group, all minor. At discharge, reocclusions were observed in 18% (12/68) of immediate-heparin patients, and 11% (3/27) of the latter. Bioassayed fibrinogen levels displayed sustained depression regardless of bleeding for 20 hours after streptokinase; however, defibrinogenation measured by immunoassay was much less striking. This suggests that high levels of fibrinogen degradation products spuriously affect the bioassay of fibrinogen. We conclude that bleeding is related to the anticoagulant effects of fibrinogen degradation products interacting with heparin, and may be largely independent of hypofibrinogenemia. Delaying heparin for 12 hours may decrease the risk of bleeding while little affecting the risk of reocclusion.

Coronary Disease↗

Isolation and characterization of resident stromal macrophages and hematopoietic cell clusters from mouse bone marrow.

In situ studies with the mouse macrophage (M phi)-specific antibody, F4/80, have shown that resident M phi in femoral bone marrow (RBMM) form hematopoietic islands with immature myelomonocytic and erythroid cells (Hume, D. A., et al. 1983. J. Exp. Med. 158: 1522). We have isolated these islands (clusters) by collagenase digestion, purified them from single cells by velocity sedimentation, and analyzed their cellular content. The clusters, ranging from 5- to 100 cells, constituted approximately 7% of the total nucleated cells, and greater than 70% contained at least one strongly staining, F4/80+ central M phi. In comparison, less than 26% showed reactivity for alkaline phosphatase, a marker of fibroblastoid reticulum cells. Compared with the nonclustering population, clusters were enriched with RBMM, fibroblastoid cells, and immature hematopoietic cells, but depleted of mature granulocytes and erythrocytes. The RBMM population was purified from other cells in clusters by selective adherence to glass and was compared with resident peritoneal M phi (RPM) for morphology and the presence of antigens, receptors, and enzymes. RBMM spread more extensively than RPM and frequently extended delicate plasma membrane processes. These and subsequent differences were not attributable to the collagenase treatment. Both M phi populations stained positively with antibodies F4/80 and 2.4G2 (Fc receptor IgG1/2b), bore mannosyl/fucosyl receptors, and showed reactivity for acid phosphatase and nonspecific esterase I. In contrast to RPM, RBMM had no detectable Mac-1 antigen (CR3) or complement receptors, but bore higher levels of Fc receptors (IgG2a and IgG2b) and Ia antigens. In addition, RBMM possessed a novel hemagglutinin activity for unopsonized sheep erythrocytes, which was not present on RPM. RBMM showed no respiratory burst activity in response to zymosan particles, but ingested them avidly. The growth properties of clustering and nonclustered populations were compared by measurement of [3H]thymidine incorporation and progenitor assays. Cells in clusters incorporated three- to fourfold more thymidine than nonclustered cells even in the absence of exogenous growth factors, and autoradiography demonstrated that RBMM made contact with proliferating cells. In contrast, the clusters contained over threefold fewer granulocyte/M phi progenitors compared with nonclustering cells. When clusters were cultivated for up to 3 d, there was rapid outgrowth of monocytes and fibroblastoid cells. These studies demonstrate that RBMM bear a distinct morphology and phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum.

We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi-derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser but nevertheless equivalent effect was observed for the three soluble inhibitors of CR3-mediated binding vs. the two soluble inhibitors of MFR-mediated binding. Modulation experiments in which either CR3 or MFR had been rendered inaccessible demonstrated that both receptors must be present on the segment of M phi membrane to which the parasite binds. The combined function of these two distinct M phi receptors may provide a general mechanism for recognition and ingestion of other pathogenic protozoa known to activate the alternative pathway.

Animals↗

Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80.

We have estimated the macrophage content of different tissues of the normal adult mouse using F4/80, a highly specific antigen marker for mature mouse macrophages. An absorption indirect binding assay was used to quantitate F4/80 antigen against a calibration standard made from the J774.2 macrophage-like cell line. The richest sources of tissue F4/80 antigen were found to be bone marrow, spleen, cervical and mesenteric lymph nodes, large bowel, liver, kidneys, and small bowel. The organs that have the highest total F4/80 antigen content are the liver, large bowel, small bowel, bone marrow, spleen, cervical and mesenteric lymph nodes, and kidney. We conclude that the mononuclear phagocyte system is mainly distributed in the gastrointestinal tract and liver, followed by hemopoietic and lymphoid tissues.

Absorption↗

Symmetric cardiac enlargement in highly trained endurance athletes: a two-dimensional echocardiographic study.

Twelve highly trained male endurance athletes and 12 normally active matched control subjects were studied by two-dimensional and M-mode echocardiography to evaluate changes in the right and left heart chambers associated with intense aerobic training. Maximal oxygen uptake, a measure of cardiovascular fitness, ranged from 62.1 to 82.6 ml/kg/min in the athletes and from 33.0 to 49.3 ml/kg/min in the control subjects (p less than 0.001). The athletes had significantly greater left ventricular wall thickness (p less than 0.01), left ventricular chamber area (p less than 0.005), left atrial area (p less than 0.01), right ventricular chamber area (p less than 0.002), right ventricular wall thickness (p less than 0.05), and right atrial area (p less than 0.01). Proportionality of cardiac chamber enlargement in the athletes was shown by similar ratios of both right-to-left ventricular areas and right-to-left atrial areas in the two groups. Left ventricular contractility was not significantly different between groups. Cardiac enlargement in endurance athletes enables a greater stroke volume for the performance of sustained, intense exercise; hypertrophy of the chamber walls normalizes wall stress. These changes occur symmetrically in both right and left cardiac chambers in the endurance athlete, reflecting bilateral hemodynamic loading. The symmetry of the endurance athlete's cardiac enlargement differs from most pathologic conditions which have heterogeneous effects on specific cardiac chambers.

Adult↗