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E L Howes

Publications and source records attributed to E L Howes.

At least 55 records · Page 3Linked to original sources
PubMed1985

Complement and polymorphonuclear leukocytes do not determine the vascular permeability induced by intraocular LPS.

The intravitreous injection of an endotoxin of Escherichia coli 055:B5 (LPS; 0.1-0.5 microgram/50 microliters of saline) induces ocular inflammation in rabbits that is maximal 20-24 hours later and disappears by 4 days. The inflammation is characterized by an alteration in ocular vascular permeability (OVP) measured by the ocular extravasation of 125I-albumin and an outpouring of leukocytes, most of which are polymorphonuclear leukocytes (PMNs), as determined by histopathologic study. Nitrogen mustard (mechlorethamine, 1.75 mg/kg) administered 3 days prior to LPS virtually eliminates PMNs in the circulation and those infiltrating ocular tissues 20 hours after intravitreous LPS, and yet the average increase in vascular permeability is not different from that of controls. Cobra venom factor (CVF; 300-400 units) 7 hours before intravitreous LPS produces a greater than 90% decrease in both hemolytic complement activity and zymosan-inducible serum chemotactic activity; yet 20 hours after LPS, the OVP is the same in CVF-treated rabbits and controls. For comparison, an ocular passive Arthus reaction (ovalbumin-anti-ovalbumin) was significantly affected by CVF pretreatment. Chemotactic activity in the aqueous humor is found in both CVF-treated and control rabbits 20 hours after intravitreous LPS. This activity attracts rabbit, but not human, PMNs, is partially heat-sensitive, and is not inhibited when PMNs are preincubated with C5a. These results indicate that neither PMNs nor circulating complement determine the OVP following intravitreous LPS, and that the chemotactic activity present in aqueous humor at the height of the inflammatory response is not primarily C5a.

Animals↗
PubMed1984

Endotoxin-induced uveitis in the rat: observations on altered vascular permeability, clinical findings, and histology.

A single intraperitoneal dose of endotoxin (lipopolysaccharide or LPS) induces an acute inflammatory response in the uveal tract of rats. This inflammation is characterized by a breakdown of the blood/aqueous barrier within 3 hr after the LPS and the subsequent development of clinical disease and a cellular infiltrate. Early change in vascular permeability, clinical, and pathological changes were dose dependent with the two highest doses (100 micrograms or 500 micrograms) producing more severe pathology. Clinical and histopathologic abnormalities peaked at 24 hr and were resolving by 48 hr. Although clinical and histologic changes correlated well, the degree of breakdown of the blood/aqueous barrier at 3 hr failed to predict the extent of the cellular exudate measured by either clinical or histologic criteria. In addition, pharmacologic suppression of the early vascular permeability changes with indomethacin, cyproheptadine, or both agents failed to protect the animals consistently from subsequently developing significant clinical disease or cellular infiltrates on histopathology. LPS-induced uveitis in the rat provides a simple, reproducible model for ocular inflammation without requiring direct eye manipulation. The mediators responsible for the early vascular permeability in this model appear to be distinct from the mediators primarily responsible for the subsequent cellular exudate.

Animals↗
PubMed1984

Ocular localization of circulating bacterial lipopolysaccharide.

A bacterial lipopolysaccharide (LPS) extracted from a rough strain of Salmonella minnesota ( Re595 ) containing primarily lipid A was used to study tissue distribution following its intravenous injection in rabbits. For this purpose, the Re595 was either labelled with 125iodine (125I) and localization quantitated by gamma radiation spectrometry and radioautography of different tissues or a fluorescein labelled antibody to Re595 was employed. Localization of [125I]- Re595 or LPS was looked for at 30 min and 2 hr after intravenous injection. [131I]-albumin was employed either to measure intravascular protein or total tissue protein and, in some studies, [131I]-albumin and [125I]-fibrinogen were used to measure protein after unlabelled Re595 . Both fractions of isotopes injected and estimates of tissue-bound Re595 were made in the whole eye, liver, spleen, kidney and lung and in isolated iris-ciliary processes, aqueous, lens, vitreous, and posterior segment (retina, choroid, and sclera). Aqueous and iris-ciliary processes, but no other tissues, showed a marked extravazation of [131I]-albumin and [125I]-fibrinogen. [125I]- Re595 was found to localize primarily in liver and spleen. At 30 min, [125I]- Re595 was found in nanogram quantities within the eye and at 2 h greater amounts of LPS were found in iris-ciliary processes and aqueous than in the posterior segment. Neither radioautography nor fluorescein-labelled antibody to Re595 showed evidence of histologic localization of LPS in the iris-ciliary processes. These results indicate that although LPS does not localize preferentially in the eye, it does accumulate in quantities sufficient to have an effect locally.

Animals↗
PubMed1984

Retinoblastoma: tissue culture lines and monoclonal antibody studies.

Retinoblastoma patients have cellular and humoral reactivity towards antigens expressed on retinoblastoma cells. We report the ultrastructural, cytogenetic, and immunologic features of four new retinoblastoma derived tissue culture cell lines. Studies with hybridoma produced monoclonal antibodies demonstrate that these lines share antigens with a previously described long-term allogeneic retinoblastoma derived tissue culture cell line, as well as with antigens on fresh retinoblastoma.

Antibodies, Monoclonal↗
PubMed1984

Characterization of endotoxin-induced C5-derived chemotactic activity in aqueous humor.

Although a cellular exudate characterizes acute anterior uveitis, few studies have sought to identify the chemoattractant(s) contributing to this phenomenon. As a model of acute ocular inflammation, the authors have injected rabbits intravenously with endotoxin (Salmonella typhimurium LPS, 2.5 micrograms/kg). In a Boyden chamber assay, aqueous humor drawn 3 hr after LPS (post-LPS aqueous) exhibited chemotactic activity for purified rabbit granulocytes (PMN). "Checkerboard" analysis indicated that chemotaxis, rather than protein-induced chemokinesis, primarily accounted for PMN migration. Aqueous from normal rabbits demonstrated no chemotactic activity. Chemotactic activity was maximal at 3 hr post-LPS (versus 1 or 5 hr). PMN migration exhibited a direct correlation with the concentration of aqueous tested (0.5-5%). Several observations indicated that this chemotactic activity is complement (C5)-derived. It is inhibited by antibodies to C5 but not affected by antibodies to C3. Similar to rabbit C5a, chemotactic activity in post-LPS aqueous was heat stable at 56 degrees C X 30 min, attracted both human and rabbit PMN at similar concentrations and induced release of beta glucuronidase from PMN. In addition, prior incubation of rabbit PMN with partially purified C5a (densensitization) specifically inhibited chemotactic responses to both C5a and post-LPS aqueous without inhibiting responses to another chemoattractant, n-formyl-methionyl-leucyl-phenylalanine. Finally, chemotactic activity from post-LPS aqueous could be recovered from a Sephadex G75 column and eluted similarly to chemotactic activity in zymosan activated rabbit serum or 13,700 D molecular weight marker. The presence of complement-derived chemotactic activity in this model should not be construed as evidence that this activity contributes to the pathogenesis of endotoxin-induced inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Antiretinoblastoma monoclonal antibodies.

Mouse-mouse somatic hybridization techniques were used to produce monoclonal antibodies directed towards antigen expressed on retinoblastoma-derived tissue culture cell lines. Four monoclonal antibodies were produced with varying avidity which were reactive against allogeneic retinoblastoma-associated antigens. Sensitivity and specificity was demonstrated using ELISA and chromium release assays. Immunofluorescent antibody studies suggest that these monoclonal antibodies may be useful diagnostically.

Animals↗
PubMed1983

Antiinflammatory effects of endotoxin. Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro.

Although capable of provoking a variety of inflammatory effects, endotoxin (bacterial lipopolysaccharide) paradoxically has been reported to be antiinflammatory. The authors have found that single intravenous injections of Escherichia coli endotoxin, 24 hours before challenge, inhibit almost completely the vascular permeability changes and exudation of polymorphonuclear leukocytes induced in rabbit skin by reversed passive Arthus reactions. Whereas intravenous injections of endotoxin also caused modest inhibition of the vascular permeability changes induced in rabbit skin by the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), exudation of polymorphonuclear leukocytes was unaffected. Polymorphonuclear leukocytes from rabbits given single injected doses of endotoxin exhibited markedly diminished chemotactic and degranulation responses to complement (C5)-derived peptides in vitro. Responses of these cells to FMLP, however, were normal. These data suggest that selective suppression of polymorphonuclear leukocyte responses to C5-derived peptides accounts, in part, for the antiinflammatory effects of endotoxin.

Animals↗
PubMed1982

Peripartum pseudomalignant myositis ossificans of the finger.

Two cases of pseudomalignant peripartum myositis ossificans of the finger are reported. The benign diagnosis is confirmed by the histologically characteristic zone phenomenon, consisting of a transition from an inner zone of proliferating spindle cells to a middle zone of well-oriented osteoid and finally to an outer zone of mature bone. In Case No. 1, because of the question of malignancy, a ray amputation was performed. In Case No. 2, the patient was observed during the peripartum period to show diminution in the size of the tumor. The lesion was eventually treated by local excision.

Adult↗
PubMed1982

Mononuclear cells in the corneal response to endotoxin.

A severe keratitis can be produced after the direct injection of bacterial endotoxin, or lipopolysaccharide (LPS), in rabbits. Corneal inflammation can progress to scarring and vascularization within a 2 to 3 week period. Pretreatment with systemic adrenal corticosteroids (triamcinolone) prevents this response. Limbal cellular and vascular events were studied during the first 20 hr after injection of LPS in treated and nontreated rabbits. Perivascular limbal inflammatory cells were counted and limbal vascular permeability was assessed by extravasation of 131I-albumin and 125I-fibrinogen in the cornea. Corticosteroids decreased but did not prevent the early protein extravasation and profoundly altered the inflammatory cell population around blood vessels at the limbus. Mononuclear cells, particularly mononuclear phagocytes, were sharply reduced. It is proposed that these cell types play an important role in the perpetuation and amplification of the inflammatory response in this reaction.

Animals↗
PubMed1982

An adoptive cell transfer system for the evaluation of immunity to Herpes simplex virus in mice.

Lymphocytes adoptively transferred from syngeneic immune donors protect mice against challenge with Herpes simplex virus type 1. Normal mice require transfer 3 x 10(7) spleen cells for protection. Sublethal irradiation (450 rad) decreases the number required five-fold. Lymphocytes from non-immune donors do not protect, and hyperimmunization does not enhance the protection efficiency of donors. The viral LD50 varies through a range 10(5)-fold during the period of recovery from this amount of radiation, but over the same period there is little variation in the number of cells required for protection. Nor is there much variation in this number between strains of mice naturally susceptible (CBA) and resistant (C57) to the virus. We conclude that natural resistance operates at a level of virus handling prior to operation of the lymphocyte system, perhaps at the generation of interferon. As few as 1.3 x 10(6) immune T lymphocytes can protect against challenge provided that they are transferred together with normal spleen cells. We conclude that primed lymphocytes act in co-operation with non-immune cells.

Animals↗
PubMed1982

Aqueous immune complexes in immunogenic uveitis.

A primary immunogenic uveitis was produced in rabbits by the intravitreal injection of bovine plasma albumin or ovalbumin. A secondary or recurrent uveitis was induced by intravenous injection of the specific soluble antigen several months after the cessation of primary inflammation. Aqueous antigen-antibody complexes were studied at times of maximal clinical response in both primary and recurrent forms during resolution of primary immunogenic uveitis, and in a nonspecific protein extravasation induced by aqueous paracentesis. Immune complexes could be demonstrated only during times of clinically evident inflammation in immunogenic uveitis. The results indicate the importance of antigen-antibody complex formation in the pathogenesis of this form of experimental ocular inflammatory disease.

Animals↗
PubMed1980

Lipid A dependence of the ocular response to circulating endotoxin in rabbits.

The effects of bacterial lipopolysaccharides on ocular vascular permeability were measured after their intravenous injection in rabbits. Alterations in ocular vascular permeability were quantitated by the accumulation of 125I-labeled albumin in the enucleated eye compared with that in heart blood (ocular albumin space). Two lipopolysaccharides extracted from Escherichia coli O111:B4, one with high lipid A content and one with high polysaccharide content, were tested initially, and the one with greater lipid A was 200 times more effective in producing an alteration in ocular vascular permeability. Lipopolysaccharide from a rough strain, Salmonella minnesota (R595), containing lipid A primarily, as well as a purified lipid A extracted from +595, were also effective. But an extract of the protein associated with lipid A was without significant effect. In vitro pretreatment of the lipopolysaccharides with polymyxin B, an inhibitor of the biological activity of lipid A through direct binding, could abrogate the ocular response. These results indicate the paramount importance of the lipid A moiety in the ocular response to circulating endotoxin.

Animals↗
PubMed1979

Mouse hybrid cell lines produce antibodies to herpes simplex virus type 1.

A solid-phase radioimmunoassay procedure has been devised for the assay of antibodies produced in the mouse to herpes simplex virus type 1 (HSV-1). It is based on the adsorption of virus to flexible micro-well plates and uses radio-iodine-labelled rabbit antibody against mouse immunoglobulin to assess antibody binding. Using this assay for screening, cell hybrids have been obtained which yield monoclonal antibody to HSV-1. The hybrids are between spleen cells from hyperimmune mice and an immunoglobulin-non-secreting, azaquanine resistant myeloma cell line (NS-1). From 480 hybrid cell lines initially examined, five stable cell lines were obtained which released HSV-1-specific antibody in vitro and in vivo. Mice carrying transplants of these cell lines yield binding titres in serum of up to 1/25000. Both IgG and IgM antibodies were obtained in this way.

Animals↗
PubMed1978

The structural basis of altered vascular permeability following intraocular inflammation.

An immunogenic uveitis was produced in rabbits by the intravitreal injection of bovine gamma-globulin. Four to six months later, an alteration in vascular permeability was determined by greater accumulation of iodinated I 125 serum albumin in the previously inflamed eye than in the normal eye. An altered vascular permeability was found only in eyes with profound structural changes. Possible sites of extravascular protein leakage were: (1) proliferated blood vessels in the posterior chamber and vitreous; and (2) leakage through the disrupted and scarred ciliary epithelium. In eyes without evidence of altered vascular permeability, a persistent chronic inflammation was observed, and gliosis and chorioretinal scarring was prominent.

Animals↗
PubMed1978

The effects of indomethacin on the generalized shwartzman reaction.

The antiflammatory drug indomethacin, an inhibitor of prostaglandin synthesis, prevents the generalized Shwartzman reaction produced in rabbits by two intravenous injections of bacterial endotoxin. Indomethacin has this effect if given before the first but not the second injection of endotoxin. Measurements of circulating white blood cells, platelets, partial thromboplastin time, prothrombin time, fibrinogen, plasminogen, and soluble fibrin were made at several times after either the first or second injection of endotoxin treated and nontreated rabbits. Four hours after the first injection of endotoxin, leukopenia and thrombocytopenia were somewhat greater in treated rabbits and the prolongation of the activated partial thromboplastin time was shortened. Twenty-one hours after injection of endotoxin, leukocytosis and elevation of plasma fibrinogen were not as great in treated animals. Four hours following the second injection of endotoxin a decrease in fibrinogen, prolongation of the prothrombin time, and the elaboration of soluble fibrin were consistently found in rabbits with the generalized Shwartzman reaction. In treated rabbits, none of these changes occurred. Indomethacin prevents the generalized Shwartzman reaction by preventing the development of the prepared state in this endotoxin model.

Animals↗