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Biomedical subjects

E W Jeffes

Publications and source records attributed to E W Jeffes.

35 records · Page 2Linked to original sources
PubMed1990

Recombinant human cytokines stimulate neutrophil adherence to IgG autoantibody-treated epithelial basement membranes.

We investigated the ability of the purified recombinant human cytokines: tumor necrosis factor-alpha (rTNF), granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin-1 beta (rIL-1), interleukin-3, and tumor necrosis factor-beta (rTNF-beta) to stimulate neutrophil adherence (NA) to basement membranes (BMs) of stratified squamous epithelia pretreated with autoantibodies (ABM) specific for the BM matrix protein, type-VII collagen. rTNF, rGM-CSF, rIL-1, and rTNF-beta, but not IL-3, stimulated NA and stimulation was ABM- and cytokine-concentration-dependent. Stimulation was cytokine-specific and not due to endotoxin since it was significantly inhibited by cytokine-specific antibodies but not by polymyxin B (PB). rTNF and rGM-CSF were the most potent stimulators, were effective at concentrations less than 0.067 ng/ml, and stimulated NA greater than 600%. Relative potency was: rTNF = rGM-CSF greater than rTNF-beta greater than rIL-1. Stimulation by rTNF was due to a rapid, time-dependent effect on the neutrophil, and NA appeared to be dependent, in part, on the low-affinity neutrophil receptor for IgG, Fc(gamma)RIII, because it could be specifically inhibited by monoclonal antibody (3G8) to Fc(gamma)RIII. These results suggest that rTNF, rGM-CSF, rIL-1, and rTNF-beta may contribute individually or in combination to immune-mediated inflammation and tissue injury by stimulating immune adherence of neutrophils to tissue-bound autoantibodies and immune complexes.

Antibodies, Monoclonal↗
PubMed1990

Identification of TNF-LT blocking factor(s) in the serum and ultrafiltrates of human cancer patients.

Human serum ultrafiltrate (UFS) obtained from cancer patients contains material(s) which inhibit the cytolytic activity of tumor necrosis factor (TNF-alpha) and lymphotoxin (LT-TNF-beta) in vitro. These factors are found in UFS from patients with different types of cancers and are not detected in the sera of normal donors. Results from molecular sizing studies demonstrated that their molecular weights are over 30 kD. They appear to block by interfering with the early stages of cell lysis. It is not clear whether or not these TNF-LT blocking factor(s) are the same molecules. These factors may have adverse effects on the biological activities of TNF and LT in cancer patients.

Clinical Trials as Topic↗
PubMed1989

The presence of antibodies to lymphotoxin and tumor necrosis factor in normal serum.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines that probably play a role in several autoimmune diseases. In this report, we describe the detection, in normal nonimmune serum, of naturally occurring antibodies that bind to recombinant human LT and TNF. The naturally occurring antibodies that bind to LT and TNF could explain why normal immunoglobulin is effective therapy in idiopathic thrombocytopenic purpura and Kawasaki syndrome.

Animals↗
PubMed1989

Adjuvant therapy of bullous pemphigoid with dapsone.

Thirteen patients with recurrent severe widespread recalcitrant bullous pemphigoid (BP) were studied. These patients had been initially treated with prednisone and azathioprine, and clinically responded. However, they frequently continued to have flare-ups or activation of the disease while still on treatment with high doses of these drugs. The addition of dapsone, as an adjuvant to the treatment, helped to produce a complete clinical remission in 12 patients (92%). In addition, there was a statistically significant difference in the median dose of prednisone, before and after the institution of dapsone, and in the maintenance dose of prednisone. Patients were tapered off prednisone more easily than before and did not flare at lower doses of prednisone as previously. It is suggested that, in patients with severe, recalcitrant, recurrent disease, the addition of dapsone to the existing regime of corticosteroids and/or immunosuppressive drugs, may be beneficial. This may be especially valuable to patients in whom corticosteroids have been used for prolonged periods and in whom increasing the corticosteroid dose further may be associated with significant side-effects.

Adult↗
PubMed1989

Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines.

The expression of lymphotoxin (LT) mRNA and cytokine in human tonsillar B cells and B cell lines was examined by Northern blots and cytotoxicity assays, respectively. In tonsillar B cells, phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan l (SAC) alone induced low levels of LT mRNA accumulation. However, SAC and anti-mu were strongly synergistic with PMA in this induction. Peak LT mRNA expression in tonsillar B cells stimulated by PMA plus SAC occurred between 48 and 72 h and was approximately half as much as that in PMA plus anti-CD3-stimulated T cells. Cyclosporine A was not effective in inhibiting LT mRNA accumulation by stimulated tonsillar B cells. A number of B cell lines could also be stimulated by PMA to express LT mRNA. Peak accumulation of LT mRNA in the cell line RPMI 1788 stimulated with PMA peaked about 8 h. A23187 in combination with PMA caused this accumulation to increase slightly and to peak earlier. The cytotoxic effects in the supernatants of stimulated B cells were contributed mostly by LT. The results indicate that tonsillar B cells are important in LT production and that there are important differences in the stimulation requirements for LT production and in LT mRNA expression kinetics between tonsillar B cells and B cell lines.

B-Lymphocytes↗
PubMed1987

Purified native and recombinant human alpha lymphotoxin [tumor necrosis factor (TNF)-beta] induces inflammatory reactions in normal skin.

These studies report findings that demonstrate that human alpha lymphotoxin (LT) induces local, visible, and microscopic inflammatory reactions in normal skin. Skin sites in rabbits, when inoculated with a single injection of native or recombinant human alpha lymphotoxin, demonstrated erythema, swelling, and warmth within 5 hr. Erythema peaked between 24 and 48 hr had resolved by 72 hr. Histologic studies of skin sites injected with native LT revealed polymorphonuclear neutrophil (PMN) infiltration and edema beginning as early as 3 hr posttreatment. Individual skin sites that received three daily injections of native LT exhibited persistent erythema and swelling. Palpable induration was evident 24 hr after the second injection in the series. Histologic examination revealed the presence of many PMNs with associated focal dermal destruction, in the form of microabscesses, and scattered mononuclear cells. In contrast, control materials and recombinant human tumor necrosis factor (TNF-alpha) did not induce visible skin reactions in the rabbit. Several additional controls excluded endotoxin as being the agent responsible for the inflammatory skin reactions observed. The ability of LT to induce inflammation may have a role in its antitumor activity and it may be an important endogenous mediator in other immunologic reactions.

Animals↗
PubMed1987

Human alpha lymphotoxin (LT): studies examining the mechanism(s) of LT-induced inflammation and tumor destruction in vivo.

Recent information from our laboratories indicates that human alpha lymphotoxin (LT) is a powerful mediator of tumor necrosis, and inflammation. Our studies indicate that LT induced effects in vivo are complex and involve multiple mechanisms(s). The data presented here suggests that LT induced tissue destructive and inflammatory reactions mediated by cytolytic and antigen reactive lymphocytes may have a role in a much broader variety of inflammatory processes than had been appreciated.

Animals↗
PubMed1984

Lymphotoxin detected in the blister fluid of bullous pemphigoid patients.

The role of lymphocytes in the pathogenesis of bullous pemphigoid was examined by assaying the blister fluid obtained from bullous pemphigoid patients for the presence of the lymphokine, lymphotoxin. Blister fluids from six bullous pemphigoid were assayed on L-929 target cells for the presence of cytolytic molecules in the standard lymphotoxin assay. Three of six blister fluids obtained from bullous pemphigoid patients and one linear IgA bullous dermatosis patient contained significant levels of cytolytic activity. Control blister fluids from suction blisters, herpes, pemphigus, and toxic epidermal necrolysis patients did not contain cytolytic activity. Serum from five bullous pemphigoid patients also had no cytolytic activity. Neutralization studies using rabbit anti-alpha-lymphotoxin demonstrated that 54 to 88% of the cytolytic activity found in bullous pemphigoid blister fluid was due to alpha-lymphotoxin. These results indicate that lymphotoxin is locally released in the skin of bullous pemphigoid lesions and is detectable in blister fluids.

Antibodies↗
PubMed1984

Acantholysis produced in vitro with pemphigus serum: hydrocortisone inhibits acantholysis, while dapsone and 6-mercaptopurine do not inhibit acantholysis.

Many studies have shown that human skin in organ cultures containing pemphigus antibody undergoes acantholysis, the histologic hallmark of pemphigus vulgaris. This in vitro organ culture system provides a good model to determine if drugs used to treat pemphigus inhibit the effect of pemphigus antibody after it is produced. In this study we determined if hydrocortisone, dapsone, and 6-mercaptopurine (6-MP) could inhibit acantholysis observed in human skin organ cultures containing high constant levels of pemphigus plasma. In six experiments we demonstrated that hydrocortisone (10(-3) and 5 X 10(-4) M) present at the start of organ culture inhibited acantholysis induced by pemphigus sera. Thus, this study raises the possibility that the large doses of steroids used to treat acute pemphigus could act directly on the skin, inhibiting acantholysis in the presence of high titers of pemphigus antibody. Other effective immunosuppressive drugs, such as dapsone and 6-MP, probably do not act directly on the skin.

Acantholysis↗
PubMed1976

Relationship of CIF, LT, and PIF released in vitro by activated human lymphocytes. II. A further functional comparison of LT and PIF activities on HeLa and L-929 target cells.

Lymphotoxin (LT), and proliferation inhibition factor (PIF) activities found in 5-day supernatants of mitogen-activated human lymphocytes (SAL) were further compared. In agreement with previous results, the activities could not be distinguished functionally. Quantitative differences in the amount of activity detected in the SAL could be accounted for on the basis of target cell differences, concentration of the lymphocyte effector molecules in the supernatant, and the parameter employed to assess cell function. Growth inhibitory activity detected at high supernatant dilutions was completely reversible, whereas the cytotoxic activity detected at low supernatant dilutions was irreversible. When the active medium was fractionated on DEAE, two peaks of inhibitory activity were detected. Depending upon the amount of activity and target cell, both peaks of activity were growth inhibitory or cytotoxic. Since both peaks of material affected HeLa and L-929 cells, the materials were not species specific. Thus, it appears that cloning inhibitor factor, LT, and PIF activities may actually be measures of the same stable materials found in 5-day activated lymphocyte supernatants.

Cell Line↗
PubMed1975

Relationship of cloning inhibition factor, "lymphotoxin" factor, and proliferation inhibition factor release in vitro by mitogen-activated human lymphoctes.

Human lymphocytes were stimulated in vitro with mitogens, phytohemagglutinin and concanavalin A to secrete proliferation inhibitory factor (PIF), cloning inhibitory factor (CIF), and lymphotoxin (LT). These three activities were demonstrable in the same supernatant, moreover, the particular effect observed was shown to depend on the concentration of the medium and the type of target cell employed. In general, the medium effects on target cells were: a) cytotoxic at high concentrations, b) growth inhibitory at intermediate concentrations, and c) only temporarily growth inhibitory at low concentrations. The absolute concentration producing a certain effect varied, depending on the target cell type employed. In addition, the sensitivity of the target cells to LT parallels the sensitivity of the cell to each of the other activities, PIF and CIF, and no species specificity was observed.

Adenoids↗
PubMedDate not supplied

Therapy of pemphigus.

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Adjuvants, Immunologic↗
PubMedDate not supplied

Methotrexate.

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Administration, Oral↗
PubMedDate not supplied

Actinic keratosis. Current treatment options.

Actinic keratoses are hyperkeratotic skin lesions that represent focal abnormal proliferation of epidermal keratinocytes. Some actinic keratoses evolve into squamous cell carcinoma of the skin, while others resolve spontaneously. The conversion rate of actinic keratosis to squamous cell carcinoma is not accurately known, but appears to be in the range of 0.25 to 1% per year. Although there is a low rate of conversion of actinic keratoses to squamous cell carcinoma, 60% of squamous cell carcinomas of the skin probably arise from actinic keratoses. The main cause of actinic keratoses in otherwise healthy Caucasians appears to be the sun. Therapy for actinic keratoses begins with prevention which starts with sun avoidance and physical protection. Sunprotection with sunscreens actually slows the return of actinic keratoses in patients already getting actinic keratoses. Interestingly, a few studies are available that demonstrate that a high fat diet is associated with the production of more actinic keratoses than is a low fat diet. One of the mainstays of therapy has been local destruction of the actinic keratoses with cryotherapy, and curettage and electrodesiccation. A new addition to this group of therapies to treat individual actinic keratoses is photodynamic therapy with topical aminolevulinic acid and light. In patients who have numerous actinic keratoses in an area of severely sun damaged skin, therapies which are applied to the whole actinic keratosis area are used. The goal of treating such an area of skin is to treat all of the early as well as the numerous clinically evident actinic keratoses at the same time. The classical approaches for treating areas of photodamaged skin without treating actinic keratoses individually include: the use of topically applied fluorouracil cream, dermabrasion, and cutaneous peels with various agents like trichloroacetic acid. Both topically as well as orally administered retinoids have been used to treat actinic keratoses but retinoids alone are probably not an optimal monotherapy. Photodynamic therapy with topical aminolevulinic acid and light is a new therapy for actinic keratoses. Aminolevulinic acid is a precursor of protoporphyrin IX (PpIX) which is synthesized in the actinic keratosis when it is treated with aminolevulinic acid, and the PpIX photosensitizes the actinic keratosis so that light exposure can lead to its destruction. Photodynamic therapy with topical aminolevulinic acid is approved in the US to treat multiple individual actinic keratoses on the face and scalp and has similar cure rates to those reported for cryotherapy and fluorouracil therapy.

Humans↗