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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 361 records · Page 20Linked to original sources
PubMed1990

Seroconversion, staging and survival. Natural history of HIV infection.

With the discovery of human immunodeficiency virus (HIV), researchers identified the etiologic agent for acquired immunodeficiency syndrome (AIDS). Although neither a cure nor a vaccine exists for this fatal disease, considerable information is now available on the progression from HIV infection through AIDS. Understanding the natural history of this progression can facilitate early detection and intervention. Although the epidemic continues to claim lives at an accelerating rate, the timely administration of prophylactic and therapeutic modalities can significantly prolong survival time for many patients. As more effective and less toxic treatments are developed, it will become increasingly crucial for practitioners to accurately diagnose and stage HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Exercise and fitness.

Exercise testing and prescription appear to play an important role in promoting health maintenance strategies for women. Multistage exercise tolerance testing provides invaluable information in assessing the patient's functional capacity. The diagnostic significance of exercise-induced ST-segment depression is tenuous, however, in women with a low likelihood of heart disease. Research suggests that numerous physiologic mechanisms act to increase fetal tolerance to the circulatory and respiratory challenges of moderate maternal exercise. Moreover, appropriately prescribed endurance exercise programs for women are associated with the same salutary effects as men. Even more encouraging is the fact that these benefits can be attained at moderate levels of exercise--if long-term compliance is maintained.

Exercise↗
PubMed1990

Field test estimation of maximal oxygen consumption in wheelchair users.

To develop a field test to estimate maximal oxygen consumption (VO2max) in wheelchair users, 30 men (means age = 34.3 years) were subjected to progressive arm-crank ergometer testing with directly measured VO2max. Additionally, they performed a modified 12-minute wheelchair propulsion test for distance. Field testing was conducted within two weeks of the VO2max determination, using a standardized wheelchair (Quickie II) on a 0.1-mile indoor synthetic running track. Average peak power output and VO2max were 540 kg.m.min-1 and 22.0 ml.kg-1.min-1, respectively. The mean (+/- 1SD) wheelchair propulsion distance was 1.11 +/- 0.24 miles. Correlation of the field test data with the VO2max was highly significant (r = 0.84; p less than .001). The regression of distance in 12 minutes plotted against VO2max yielded the following equation: wheelchair propulsion (miles) = 0.370 + 0.0337 (VO2max, ml.kg-1.min-1), where the standard error of estimate = 0.13. These findings suggest that field testing can provide a good estimate of VO2max in selected wheelchair users.

Adult↗
PubMed1989

Identification of tissue factor in two human pancreatic cancer cell lines.

We have studied the effects of two human pancreatic cancer and two human small cell lung cancer cell lines on clotting and platelet aggregation. Both pancreatic lines markedly shortened recalcification times and induced platelet aggregation. The lung cancer lines produced little shortening of recalcification times and no platelet aggregation. The clotting and aggregation activities of the pancreatic lines were further characterized. Recalcification times following the addition of cancer cell line material to plasmas deficient in factors VII and X were markedly prolonged, suggesting that the activity is due to tissue factor. Hirudin, an inhibitor of thrombin from the saliva of leeches, and rabbit polyclonal immunoglobulin G anti-bovine brain tissue factor inhibited both procoagulant and aggregation activities. Apyrase (an enzyme degrading ADP), diisopropylfluorophosphate (a serine protease inhibitor) and L-trans-epoxysuccinylleucylamido(4-guanidino)butane (a cysteine protease inhibitor) failed to inhibit these activities. Increasing concentrations of heparin inhibited platelet aggregation. Subcellular fractionation studies showed these activities to be localized to the plasma membrane. The association between mucin and the acceleration of clotting has been well described. The absence of mucin in electron micrographs of these pancreatic whole cells, membrane fractions, and shed microvesicles, as well as the failure of chaotropic agents (i.e., agents stripping material extrinsic to the cell membrane such as mucin) to abrogate this activity support these activities being intrinsic to the plasma membrane. These data strongly suggest that these activities are due to tissue factor which appears to be released as microvesicles in vitro. The release of tissue factor via microvesicles in vivo is one possible mechanism for the coagulopathy sometimes seen in patients with pancreatic carcinoma.

Adenocarcinoma↗
PubMed1989

Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells. Absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells.

Treatment of mice with a rat mAb (5C6) specific for an epitope of the type 3 complement receptor of myelomonocytic cells severely interfered with the ability of the mice to resist infection with Listeria monocytogenes. Consequently, a sublethal infection was rapidly converted to a lethal one that resulted in death in 5 d. However, infection was only exacerbated if 5C6 was given earlier in infection, before mononuclear phagocytes populated sites of Listeria implantation in the liver and spleen. If given after day 3 of infection, 5C6 caused only a temporary increase in bacterial multiplication. The infection-enhancing effect of 5C6 was associated with failure of mice to focus mononuclear phagocytes at sites of bacterial multiplication of Listeria in liver hepatocytes and extracellulary in the spleen. This resulted in unrestricted multiplication of Listeria in hepatocytes and extracellularly in the spleen. The results are in keeping with the ability of 5C6 to inhibit the accumulation of myelomonocytic cells in peritoneal inflammatory exudates, as revealed by a previous study.

Animals↗
PubMed1989

Inhibition of cancer procoagulant by peptidyl diazomethyl ketones and peptidyl sulfonium salts.

Cancer procoagulant (CP) is a cysteine proteinase from cancer cells that initiates blood coagulation. Members of two classes of unique and highly specific cysteine proteinase inhibitors, peptidyl diazomethyl ketones (PDK) and peptidyl sulfonium salts (PSS), were studied to determine whether or not they inhibited CP. The inhibitors did not impair the activity of the coagulation system. There was a differential inhibitory effect of the 6 PDK and 2 PSS inhibitors, influenced by the amino acid composition or sequence of the peptide moiety, that suggests differences in structural features of the active site of CP and papain. CP was inhibited by both classes of inhibitors.

Animals↗
PubMed1989

Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172.

Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti-Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.

Antigen-Antibody Reactions↗
PubMed1989

Mouse macrophage hemagglutinin (sheep erythrocyte receptor) with specificity for sialylated glycoconjugates characterized by a monoclonal antibody.

An inhibitory rat mAb, SER-4, has been raised to the mouse macrophage (M phi)-restricted hemagglutinin, sheep erythrocyte receptor (SER), which binds unopsonized sheep erythrocytes through recognition of sialylated glycoconjugates. This receptor was originally defined on mouse resident bone marrow M phi where it was implicated in adhesive interactions of these cells with proliferating hematopoietic cells. In the present study using mouse serum-induced thioglycollate-elicited peritoneal M phi (TPM) as a model system for SER expression, mAb SER-4 IgG2a completely blocked rosette formation at 1 microgram/ml. The inhibition was likely to be via steric hindrance rather than through a direct interaction with the putative sialic acid binding site of SER because F(ab')2 and Fab fragments of mAb SER-4 gave a maximum inhibition of 50-60% and 0% respectively, despite binding effectively to the SER-4 antigen (Ag). Immunoprecipitation and Western blotting experiments with cultured M phi or tissue extracts demonstrated that the Ag recognized by SER-4 mAb is a single chain molecule with an apparent Mr by SDS-PAGE of 185 x 10(3) (reduced) or 170 x 10(3) (non-reduced) and is distinct from members of the leukocyte common Ag family. Expression of SER and SER-4 Ag in culture were closely correlated and depended on the presence of mouse serum for optimal induction. Further evidence that the SER-4 Ag is functionally equivalent to SER was provided by immunocytochemistry in which the overall pattern of staining in tissues was consistent with previous rosetting experiments. In the bone marrow, expression of the SER-4 Ag was restricted to the resident bone marrow M phi population with no expression on monocytes. High expression was also observed on stromal M phi within the subcapsular sinus and medullary cords in lymph nodes and on marginal metallophils in the spleen. These results therefore confirm that SER is a novel M phi-restricted receptor whose distribution and properties indicate a role in cellular interactions in hematopoietic and lymphoid tissues.

Animals↗
PubMed1989

Antibody to the murine type 3 complement receptor inhibits T lymphocyte-dependent recruitment of myelomonocytic cells in vivo.

We have used the delayed-type hypersensitivity (DTH) response to SRBC or tuberculin to examine the role of the murine type 3 complement receptor in T lymphocyte-dependent inflammatory recruitment. Intravenous injection of 5C6, a CR3-specific rat mAb known to impair myelomonocytic adhesion, divided the DTH to SRBC in actively immunized mice into two phases. The early phase, which lasted 24 h, was characterized by maximal oedema and maximal inflammatory recruitment and was 5C6 inhibitable. The later phase was 5C6 resistant and reached a peak 48 h after antigenic challenge and was superimposable on the declining peak seen in control mice. Passive transfer of reactive T cells mixed with antigen was used to examine the myelomonocytic effector arm of the DTH alone. Both passive transfer of cutaneous DTH to SRBC and passive transfer of the largely monocytic T cell-dependent recruitment to tuberculin in the peritoneal cavity were completely abolished by systemic 5C6 treatment. Injection of 5C6-treated donor leukocytes at the site of passive transfer had no effect. Treatment of donor mice with 5C6 at the time of active immunization did not alter their ability to provide reactive T cells for passive transfer. The myelomonocyte-restricted rat mAb 7/4 and the rapidly cleared F(ab')2 fragment of 5C6 showed no inhibition of the DTH. In all cases, inhibition of footpad swelling correlated with histological evidence of inhibition of myelomonocytic cell recruitment. Peritoneal cell counts after local DTH to tuberculin showed complete inhibition of monocyte recruitment. We conclude that CR3 plays a quantitatively important role in T cell-dependent inflammatory recruitment. This is absolute in passive transfer experiments, but only partial after active immunization. Leukocyte CR3 plays a common role in both immunologically specific and nonspecific inflammatory recruitment and provides a target that could possibly be manipulated to therapeutic advantage.

Animals↗
PubMed1989

Microglia in the neurohypophysis associate with and endocytose terminal portions of neurosecretory neurons.

The rat neurohypophysis contains a population of microglial cells, the majority of which occupy a pericapillary position in the resting gland. The microglia are immunocytochemically identifiable by the presence of macrophage-associated antigens and resemble microglia of the CNS. Morphometry at light and electron microscopic levels reveals that such cells constitute approximately 19% of the intrinsic cell population, excluding the endothelial cells. Two other populations of neurohypophysial glial cells, parenchymatous pituicytes and fibrous pituicytes, do not express macrophage-associated antigens. The microglia have long processes which surround and, in some cases, engulf apparently viable portions of the magnocellular neurosecretory nerve terminals. A sequence of stages of selective endocytosis and degradation of the engulfed nerve terminals can be visualized within pericapillary microglia. Some phagosomes and secondary lysosomes contain morphologically intact neurosecretory granules; others contain partially destroyed neurosecretory granules or amorphous material all of which are identifiable as originating from the magnocellular neurosecretory terminals by their immunoreactivity for oxytocin- or vasopressin-neurophysin. This finding indicates a novel role for the microglial cells in remodelling terminal aborizations of neurosecretory neurons and in processing or degrading hormones and peptides they contain. Because of their close and selective associations with other cellular elements of the neurohypophysis, any substances produced by microglia also have the potential to influence hormone secretion, pituicyte proliferation and neurohypophysial vasculature.

Animals↗
PubMed1989

Glucocorticoid receptor regulation: the effects of adrenalectomy, exogenous glucocorticoid, and stress on hepatic receptor number in male and female mice.

Although glucocorticoids are known to regulate their own receptor number, the physiologic significance of this process is not known. In order to assess this process in intact animals the effects of adrenalectomy, stress, and exogenous glucocorticoid on the number of hepatic glucocorticoid receptors in Swiss-Webster mice were evaluated. In males 24 hr after adrenalectomy there was a clear 2- to 2.5-fold increase (upregulation) in glucocorticoid receptor number. Conversely, 24 hr after the ip administration of exogenous corticosterone there was a clear downregulation of receptor number. In each case (upregulation and downregulation) female mice were much less responsive than males. Three stressors were used to evaluate the effect of the endogenous secretion of glucocorticoids on downregulation. Male mice were exposed to ether, vibration, and confinement either once or daily for periods up to 3 days. Animals were sacrificed 24 hr after the last stress and hepatic receptor number was compared to an unstressed control. Cytosolic receptor number was not influenced by any of these stimuli. It is concluded that although glucocorticoids clearly regulate glucocorticoid receptor number, as demonstrated by adrenalectomy and the administration of steroids to adrenalectomized animals, the physiologic significance of this process is uncertain as receptor number does not appear to be changed by stimuli of adrenal glucocorticoids in the intact animal.

Adrenalectomy↗
PubMed1989

The epidemiology of Pseudomonas aeruginosa in oncology patients in a general hospital.

Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.

Female↗
PubMed1989

Myelofibrosis in primary myelodysplastic syndromes: a clinico-morphological study of 10 cases.

We describe 10 cases of primary myelodysplastic syndrome in which marrow fibrosis was striking at presentation. All the cases showed trilineage dysplasia with increased megakaryopoiesis and marked reticulin fibrosis. Significant organomegaly was notably absent. This association has hitherto not been highlighted and it is important to distinguish these cases from those of idiopathic myelofibrosis with which they may be confused. Furthermore, their comparatively long survival distinguishes these cases from those previously described as acute myelodysplasia with myelofibrosis and malignant myelosclerosis. The pathogenesis of fibrosis in these cases may be related to disordered megakaryopoiesis and the platelet-derived cytokines that may be released. The treatment of these fibrotic cases remains problematical and further investigation is required.

Adult↗
PubMed1989

Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve.

Wallerian degeneration of the distal stump of a severed peripheral nerve involves invasion by myelomonocytic cells, whose presence is necessary for destruction of myelin and for initiating mitosis in Schwann cells (Beuche and Friede, 1984). Degeneration of the distal ends of the axons themselves is assumed to occur by autolytic mechanisms. We describe a strain of mice (C57BL/6/Ola) in which leucocyte invasion is slow and sparse. In these mice, confirming Beuche and Friede, myelin removal is extremely slow. A new finding is that axon degeneration is also very slow. This is a consequence of lack of recruitment of myelomonocytic cells for if such recruitment is prevented in other mouse strains by a monoclonal antibody against the complement type 3 receptor (Rosen and Gordon, 1987) axon degeneration is again slowed. We have also, surprisingly, found that nerve regeneration in the C57BL/6/Ola mice is not impeded by the presence of largely intact axons in the distal stump and absence of recruited cells, myelin debris and the absence of Schwann cell mitosis.

Journal Article↗
PubMed1989

Differential expression of membrane sialoglycoproteins in exudate and resident mouse peritoneal macrophages.

Wheat germ agglutinin (WGA) has been used to define biochemical differences between exudate and resident macrophages in the peritoneal cavity of mice. Western blotting with 125I-WGA identifies a restricted set of glycoproteins in elicited peritoneal macrophages (M phi) (recruited with thioglycollate or periodate) and fully activated M phi (recruited with live Bacille Calmette-Guérin, or heat-killed Corynebacterium parvum); the major species migrates with Mr 89-115 kDa in 10% acrylamide gels. These glycoproteins are not detected in resident peritoneal M phi, nor in thymocytes, neutrophils, lymphocytes and a variety of non-M phi cell lines. The binding of WGA is sensitive to neuraminidase, which exposes binding sites on these proteins for peanut agglutinin and reduces their electrophoretic mobility; these features are typical of O-linked sialo-oligosaccharides. In culture, exudate M phi increase their WGA-binding content over 48 h, and continue to display a phenotype distinct from that of resident peritoneal M phi. The stable differential expression of these sialoglycoproteins, by elicited and activated versus resident peritoneal M phi, suggests that biochemical modification during the synthesis and expression of membrane glycoproteins accompanies M phi recruitment to an inflammatory focus.

Animals↗
PubMed1989

A comparison of growth regulation of mammalian with amphibian lens epithelium.

In frogs hypophysectomy causes cell proliferation in lens epithelium to subside entirely, with better than 95% of the cells arresting in G1. The phenomenon has been traced to the action of insulin-like growth factors (IGFs) whose synthesis depends on anterior pituitary hormones, most notably GH. Both GH and purified somatomedin C can reinitiate mitosis in the lenses of hypophysectomized frogs. The present studies were done to determine if growth of rat lenses is controlled as is that of amphibia. It appears this may not be so because hypophysectomy has no effect on division in the rodent system. Protein calorie malnutrition (PCM) reduced the mitotic index and this effect is much enhanced by pituitary ablation. Of interest too, were the observations that the glucocorticoid, dexamethansone, is inhibitory in frog; the effect in rat is uncertain. Injection of bovine pituitary powder has no influence on rat while stimulating the amphibian material. It is therefore possible to modify growth of rat lens epithelium in vivo but the regulating mechanism(s) appears to be distinct from that operating in frogs. Whether the difference(s) is inherent in the cells themselves or is to be sought in the access routes through which they are reached by blood borne factors (e.g. permeability of blood-aqueous barriers) is, at present, unclear.

Animals↗