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Biomedical subjects

I Green

Publications and source records attributed to I Green.

At least 19 recordsLinked to original sources
PubMed1992

Rhinovirus 39 infection in allergic and nonallergic subjects.

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Humans↗
PubMed1992

Cloning, expression and characterization of ovine interleukins 1 alpha and beta.

Ovine interleukin 1 alpha (IL-1 alpha) c-DNA, obtained by polymerase chain reaction, has been cloned into pTZ18R and pTZ19R. The resulting DNA sequence shows close homology with the bovine sequence. The derived amino-acid sequence shows conserved motifs similar to those observed in all species studied so far. No signal peptide is seen. Northern blots of RNA from lipopolysaccharide (LPS)-stimulated ovine alveolar macrophages show IL-1 beta m-RNA to be produced earlier than and to be more transient than IL-1 alpha m-RNA. c-DNAs coding for the IL-1 alpha proprotein and IL-1 alpha and IL-1 beta mature proteins have been cloned and expressed in the yeast Ty-VLP system as fusion proteins. The resultant IL-1 protein preparations, cleaved from their fusion partners by the action of activated coagulation Factor Xa, are 80-95% pure and show biological activity in standard thymocyte co-mitogen and cartilage degradation assays for IL-1. Some species specificity is observed in that sheep thymocytes are more responsive to ovine rIL-1 than are mouse thymocytes. The presence of a Factor Xa cleavage site in the IL-1 alpha proprotein suggests that Factor Xa may be involved in the processing of ovine IL-1 alpha to its mature form.

Amino Acid Sequence↗
PubMed1991

Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer.

Levamisole has been used in a wide array of clinical research and treatment settings over the past two decades, ranging from such diseases as helminthic infestations to various autoimmune diseases. Numerous preclinical evaluations and clinical trials with levamisole in the cancer arena have been sponsored by the National Cancer Institute and other agencies worldwide with the hopes of demonstrating anticancer activity. Trials in advanced breast cancer, lung cancer, colorectal cancer, melanoma, and lymphoproliferative diseases have generally been negative or inconclusive. However, there is some indication that levamisole may be useful by itself as an adjuvant therapy for resected melanoma; recently it has been shown to be effective in combination with fluorouracil (5-FU) as adjuvant therapy for tumor-node-metastasis (TNM) stage III (Dukes' C) colon carcinoma. In the aggregate, the past 20 years of clinical experience with levamisole has resulted in as many questions as answers. However, further testing of the anticancer activity of levamisole can be expected in clinical research trials over the next few years. Hopefully, these future trials will include studies of the mechanisms of action of this agent.

Animals↗
PubMed1989

Preferential proliferation of immature B lineage cells in long-term stromal cell-dependent cultures with IL-4.

IL-4 influences the cellular composition of stromal cell dependent long term cultures. In bone marrow-derived long term lymphoid cultures initiated in presence of IL-4, the majority of cells exhibited a more immature phenotype than is usually seen in lymphoid cells grown in Whitlock-Witte type cultures. This immature cell population, lacking the B220 Ag, was purified by cell sorting. When transferred to mixed stromal layers used in conventional lymphoid long term cultures, these cells differentiated into B lineage cells that could be identified by expression of the B220 Ag and surface IgM. Abelson murine leukemia virus-transformed cell lines resulting from this immature cell population express a DJH rearrangement and contained RNA that hybridized with a VJ558 probe, suggesting transcription of germ-line V genes. A culture modification allowed selective proliferation of a non-transformed cell population with characteristics of very immature B lineage cells. The proliferation of these cells was supported by a homogeneous stromal cell line that was propagated with horse serum in presence of IL-4. The lymphoid cells proliferating under those culture conditions expressed the Ag detected by the BP-1 and 6C3 mAb and were Fc gamma RII and Ia-positive. However, more mature B cell markers were lacking. DNA analysis of these cell lines revealed JH rearrangement without evidence for deletion of any member of the DSP-2 family. These cell lines retained their immature phenotype after transfer to mixed stromal layers of Whitlock-Witte type. The mechanisms providing these unique culture conditions initiated by IL-4 in bone marrow stromal cells are discussed.

Abelson murine leukemia virus↗
PubMed1989

Interleukin-4 induces a substance in bone marrow stromal cells that reversibly inhibits factor-dependent and factor-independent cell proliferation.

Bone marrow-derived stromal cell monolayers pretreated with recombinant interleukin-4 (IL-4) inhibit the growth of hematopoietic cells. This was demonstrated by inhibition of fresh bone marrow-derived, IL-3-induced soft agar colonies as well as by inhibition of proliferation of IL-3-dependent cell lines and of a Friend virus-transformed erythroleukemic cell line. Pretreatment of stromal cells with IL-4 for five to seven days induced the inhibitory activity. IL-4 could then be removed before "plating" the bone marrow cells in soft agar, indicating that the inhibitory activity did not depend on the action of IL-4 on the precursors of the soft agar colonies. The inhibitory activity appears to be mediated by a soluble factor since inhibition was achieved even if the stromal cell layer was separated from the colony forming cells by an "empty" agar layer. However, supernatants of IL-4-induced stromal cell layers had no detectable inhibitory activity. The inhibitory action of the IL-4-pretreated stromal cell lines was not the result of killing of the precursor cells since it could be reversed if the agar layer containing the colony-forming cells was removed from the stromal cell layer and cultured with IL-3. Hydrocortisone (HC) blocked the inhibitory effect if added either in the IL-4 preincubation phase or during the colony formation stage, implying that HC blocked both induction of the inhibitory activity and its release or its effector function. A homogenous long-term stromal cell line could not be induced to exert the inhibitory activity; partial inhibition could be achieved with pure macrophages stimulated with IL-4 and CSF-1, suggesting that the inhibitory activity induced by IL-4 in mixed stromal cell layers may depend on a complex mechanism involving more than one cell type. Northern analysis of RNA from IL-4-induced and uninduced stromal cells indicated that IL-4 did not upregulate expression of CSF-1 or transforming growth factor-beta (TGF-beta) and only modestly increased expression of tumor necrosis factor, suggesting that these cytokines were not responsible for the inhibitory activity. The capacity of IL-4 to induce inhibitory activity in stromal cell layers suggests that IL-4 may play a role in the regulation of hematopoiesis.

Animals↗
PubMed1988

Multifocal extraosseous eosinophilic granuloma of the head and neck.

Multifocal eosinophilic granuloma (Hand-Schüller-Christian disease) confined to soft tissues in the head and neck region is described in a man, 32 years of age. The lesions were detected at varying time intervals within a period of 14 months. They were located in the gingivae, the submaxillary salivary glands, the thyroid gland, and in the dermal lining of the external auditory meatus. Clinical, histologic, ultrastructural, and immunohistochemical findings are presented and discussed. Some of these findings go along with the tenet that the typical proliferating histiocyte in eosinophilic granuloma is a pathologic Langerhans' cell, or a close kindred to it.

Adult↗
PubMed1988

Modulation of endothelial cell synthesis of von Willebrand factor by mononuclear cell products.

Von Willebrand factor (vWf:Ag) is an important product of endothelial cells whose major known functions are coagulation and platelet adhesion. It appears to behave as an acute-phase reactant, levels being elevated in the plasma in a wide variety of inflammatory disorders and in the extravascular compartment in at least some of them. To determine if products of mononuclear cells, activated as part of these disease processes, may directly influence the synthesis and or release of this substance, confluent human umbilical vein endothelial cells were cultured in the presence of supernatants of mononuclear cells undergoing a mixed lymphocyte reaction, and a variety of other purified or recombinant mediators including interleukin-1 (IL-1), interleukin-2, gamma-interferon and prostaglandin E2. The endothelial cell supernatants were then assayed for vWf:Ag levels using a sensitive enzyme-linked immunoassay. The results of this study demonstrate that supernatants of a mixed lymphocyte reaction increase the synthesis and or release of vWf:Ag from endothelial cells in culture by about 100-150%. As these supernatants did not cause any increase in the release of radioisotope from 51Cr-labeled endothelial cells, it appears very unlikely that this increase was simply due to the passive release of this material from dead and dying cells. Increased vWf:Ag release was also demonstrable with purified IL-1 but not with any of the other mediators tested. These results suggest that IL-1 is able to increase the release of vWf:Ag from endothelial cells largely by an increase in synthesis and indicate at least one mechanism whereby mononuclear cells, activated during the course of an inflammatory response, may be able to influence coagulation and platelet function.

Cells, Cultured↗
PubMed1987

Role of B cell stimulatory factor 1/interleukin 4 in clonal proliferation of B cells.

B cell stimulatory factor 1 (BSF-1)/interleukin 4 (IL-4) has striking effects on colony formation in soft agar by small resting B lymphocytes. BSF-1 alone induces colony formation in this cell population, presumably in costimulation with a mitogenic substance present in bacto-agar. In costimulation with anti-IgM antibodies, BSF-1 caused initial proliferation of 8 to 10% of B cells, resulting in a large number of cell clusters (10 to 40 cells/clone) after 3 to 4 days of incubation. However, substantial number of colonies (greater than 40 cells/clone) developed only from these clusters when IL-1 was added to the cultures. Using a modified immunoperoxidase staining technique for the determination of IgM allotype, evidence was obtained that B cell colonies stimulated with BSF-1 are derived from a single progenitor cell. Neutralization of BSF-1 with 11B11 after a culture period of 1 to 4 days inhibits further proliferation of B cell colonies, indicating that the action of BSF-1 extends for several cell generations beyond initial stimulation from the resting state. Furthermore, it is demonstrated that the synergistic action of IL-1 with BSF-1 is confined to the late culture period, indicating a growth-promoting effect by IL-1 for activated B cells.

Animals↗
PubMed1987

Whole ricin and recombinant ricin A chain idiotype-specific immunotoxins for therapy of the guinea pig L2C B cell leukemia.

The therapeutic efficacy of whole ricin, or recombinant ricin A chain, coupled to a monoclonal antibody that reacts with the idiotype of the surface IgM expressed on guinea pig L2C lymphoblasts, was assessed. In vitro studies were done to characterize the immunotoxins (IT) and to demonstrate their specificity before use in vivo. The concentration of whole ricin IT (M6-Ricin) that inhibited protein synthesis by 50% (IC50) in L2C cells was 1.4 X 10(-9) M, in a 5-hr assay, in the presence of lactose to block non-antibody-directed toxicity. M6-Ricin did not inhibit protein synthesis in two control guinea pig cell lines that did not express the idiotype, nor did a whole ricin IT prepared with an isotype-matched monoclonal antibody of irrelevant specificity inhibit protein synthesis in L2C cells. Two recombinant ricin A chain IT, which differed from one another by a factor of 2 to 3 in the number of A chains conjugated per antibody molecule, were less effective in vitro than M6-Ricin (IC50 of greater than 5 X 10(-8) M). For in vivo experiments, the IT were given by the i.p. route 24 hr after the i.p. inoculation of 1 X 10(5) L2C cells. The highest doses of M6-Ricin and M6-Ricin A chain IT tested, 30 micrograms/kg and 3000 micrograms/kg, respectively, were within fourfold to fivefold of their maximum tolerated doses; no deaths or ill effects due to ricin toxicity were noted. These doses increased the median survival time of L2C-bearing guinea pigs to 31 to 34 days, compared with 15 days for untreated animals. This magnitude of increase in survival indicates that 99.999% (5 logs) of injected tumor cells were eliminated, thus accounting for the 12% long-term survival rate obtained. Median survival times for guinea pigs treated with 30 micrograms/kg of the A chain IT were 18 and 21 days for the two conjugates tested, and the median survival for guinea pigs treated with 3000 micrograms/kg of unconjugated antibody was 18 days. Our data demonstrate that recombinant A chain IT are active in vivo and that the B chain of ricin can potentiate IT activity in vivo. Although the potency differs by 100-fold, the therapeutic index of the intact ricin IT is similar to that of the ricin A chain IT.

Animals↗
PubMed1987

Generation of lymphokine-activated killer cells in strain 2 guinea pigs and their use in the therapy of L2C, an acute B-cell leukemia.

Lymphokine-activated killer (LAK) cells were induced by incubating strain 2 guinea pig splenocytes or lymph node-derived cells in recombinant human interleukin-2 (IL-2) for 3-5 days. These effector cells had the morphology of lymphoblasts and were able to lyse murine P815 tumor cell targets. Fresh, unstimulated, guinea pig effectors were not capable of lysing these targets. The therapy of the L2C leukemia, an acute B-lymphoblastic leukemia of strain 2 guinea pigs, using LAK cells and recombinant IL-2 was examined. Antitumor effects were demonstrated by premixing LAK and tumor cells prior to intradermal injection in Winn type assays and then measuring the growth of local tumor and survival of the animals. In further experiments i.p. administration of LAK cells, 4 h following tumor cell inoculation by the i.p. route, prolonged the survival of treated animals. The best results in this i.p. therapy model were obtained with a 10-fold excess of LAK cells over tumor cells plus additional treatment with 1000 units of IL-2 for 20 days. This resulted in a 10-day increase in median survival of treated animals. Despite these in vivo antitumor effects, lytic activity of LAK effector populations against L2C targets could not be demonstrated in vitro. The potential synergy between LAK cells, IL-2, and a monoclonal antibody directed against the idiotype of the neoplastic cell surface immunoglobulin was also investigated. In these experiments enhanced survival of the combined treatment group, beyond that of either singly treated group, was not found. This study shows that LAK cells are useful agents in the therapy of a widely disseminated, aggressive, B-cell lymphoblastic leukemia. The use of such effectors, even in cases where in vitro lysis of the target tumor cell cannot be demonstrated, is encouraged by these results.

Animals↗
PubMed1987

Effect of a hypoglycaemic agent M&B 39890A on glucagon secretion in isolated rat islets of Langerhans.

Administration of the compound M&B 39890A lowered serum glucose levels significantly (p less than 0.001) in genetically obese mice, while no effect on serum insulin levels was observed. In in vitro experiments with isolated rat islets of Langerhans M&B 39890A inhibited arginine-stimulated glucagon release at all concentrations tested (0.5, 5.0 and 50 mumol/l). Insulin secretion was not inhibited by M&B 39890A (0.5 and 5.0 mumol/l), but was slightly decreased at 50 mumol/l. M&B 39890A (5 mumol/l) also inhibited glucagon secretion in vitro in the presence of 2 mmol/l, 6 mmol/l and 20 mmol/l glucose, while exerting no effect on insulin secretion. These results suggest that the hypoglycaemic action of M&B 39890A may be due to its direct and selective effect on glucagon secretion; this appears to operate by a mechanism different to that of glucose.

Animals↗
PubMed1987

Fever and increased serum IL-1 activity as a systemic manifestation of acute phototoxicity in New Zealand White rabbits.

Ultraviolet (UV) radiation is a significant environmental hazard for humans and animals. Although the clinical effect of an acute UV exposure such as cutaneous inflammation, malaise, somnolence, chills, and fever have been appreciated for many years, the underlying mechanisms mediating these effects are poorly understood. Since chills and fever are the most dramatic systemic sequelae after a prolonged exposure to UV, we specifically examined the effect of whole-body UV irradiation on core body temperature and serum endogenous pyrogen activity of New Zealand White rabbits, correlating this with serum interleukin 1 (IL-1) activity and alterations of serum divalent cation levels. We found that an acute dose of UV irradiation (Westinghouse FS-40 lamps, 0.2 mJ/cm2/s X 8 h) resulted in a significant increase in the core body temperature 2 h post UV (0.8 degree C), peaking 5 h post UV (1.8 degree C), and returning to normal 24 h post UV. Likewise, the sera from the UV-irradiated rabbits had significant endogenous pyrogen activity when transferred into naive recipient animals, causing an increase in core body temperature within 45 min (0.65 +/- 0.12 degree C), decreasing over the next 2 h, and returning to normal 6 h post injection. No endotoxin contamination was detected in any serum samples. This post-UV febrile response was accompanied by a prolonged increase in serum IL-1 activity (5-10 X) and a significant alteration in serum divalent cation levels, with the rabbits becoming euthermic even as the serum IL-1 levels remained elevated. These findings provide new information concerning the pathogenesis and kinetics of these systemic effects after an acute dose of UV irradiation.

Acute Disease↗
PubMed1987

Paraganglioma of the supraglottic larynx.

Supraglottic paraganglioma is described in an 80-year-old woman who presented with a small shiny-red mass at the posterior aspect of the left aryepiglottic fold. Histological examination revealed the typical 'zellballen' pattern of extra-adrenal paragangliomas. The tumor was locally excised and did not recur at 24 months follow-up.

Aged↗
PubMed1987

Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells.

B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7-20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors.

Animals↗
PubMed1986

Expression of specific binding sites on Candida with functional and antigenic characteristics of human complement receptors.

Receptors for C3 degradation fragments (CR1, CR2, and CR3) are present on many human cells including phagocytes and lymphoid cells and may be critical in the attachment of invading microorganisms. In these studies Candida were found to mimic the human CR by binding erythrocytes coated with specific human C3 fragments. Yeast forms of Candida species were adhered to glass slides and were allowed to germinate. Sheep erythrocytes (E) were coated with IgM (EA) and human complement components to prepare EA, EAC14, EAC3b, EAC3bi, and EAC3d. These test cells were then examined for adherence to the organism. Antibodies to human CR1, CR2, and CR3 were used to evaluate their potential for blocking adherence of the test erythrocytes to Candida. Fluorescein-labeled antibodies to human complement receptors were also used to characterize the binding sites. EAC3bi and EAC3d, but not E, EA, or EAC14, bound extensively to the germ tubes and pseudohyphae of Candida albicans and C. stellatoidea. EAC3b bound infrequently. Other Candida species, generally considered less pathogenic, bound significantly fewer specific test erythrocytes than C. albicans. Monoclonal antibodies to human CR1 and CR3 (3D9, 1B4, C511, 2B6, anti-B2, Mo1, and anti-Mac-1), in general, did not block adherence of test erythrocytes. Blocking of adherence of EAC3bi and EAC3d test erythrocytes coated with small quantities of C3 fragments occurred with high concentrations of monoclonal (anti-CR2) HB-5 and polyclonal (anti-CR2) anti-GP 140. Immunofluorescence studies demonstrated binding of Mo-1 to the germinated forms of the organism, whereas binding of the other antibodies was not seen. These studies suggest a surface constituent on the organism similar to CR on human cells. Additional studies are necessary to further define the molecular nature of the binding site. The ability of organisms to mimic human CR may be more generalized than previously known and may serve as a mechanism for modification of the inflammatory and immune response.

Antibodies, Monoclonal↗