Journal of biological response modifiers最新文献

{"title":"Alpha-interferon therapy for lymphoproliferative disorders developing in two children following bone marrow transplants.","authors":"M E Trigg,&nbsp;P de Alarcon,&nbsp;S Rumelhart,&nbsp;M Holida,&nbsp;R Giller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Two children developed lymphoproliferative processes following marrow transplantation. One of the two lymphoproliferative processes was documented to be Epstein-Barr virus (EBV)-associated. Both children received an extended course of alpha-interferon and gammaglobulin and responded with the disappearance of the lymphoproliferative process. Side effects from the alpha-interferon were minimal. Previous experience with EBV-associated lymphoproliferative processes following marrow transplantation have been usually fatal. This report further substantiates that alpha-interferon has a role in the treatment of EBV-associated lymphoproliferative processes following marrow transplantation.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"603-13"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13628234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of low doses of interleukin-2 injected perilymphatically and peritumorally in patients with advanced primary head and neck squamous cell carcinoma.","authors":"P Musiani,&nbsp;E De Campora,&nbsp;S Valitutti,&nbsp;F Castellino,&nbsp;C Calearo,&nbsp;G Cortesina,&nbsp;M Giovarelli,&nbsp;C Jemma,&nbsp;A De Stefani,&nbsp;G Forni","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>For 10 days, four patients with advanced squamous cell carcinoma of the head and neck received two daily injections of 100 units of natural IL-2, one around the tumor, the second near the tumor-draining lymph nodes. No side effects were observed. Histologic and ultrastructural examination of tumor and lymph nodes recovered at surgery showed that in many instances neoplastic cells were intermingled with numerous lymphocytes and eosinophils. Lymph nodes displayed hyperplasia of both cortical and paracortical areas and epithelioid venules infiltrated by lymphocytes and granulocytes. In a few cases, a decrease or disappearance of neoplastic lesions was also documented both clinically and histologically.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"571-8"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13742072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct antitumor mechanisms of recombinant interleukin-2 on recombinant interleukin-2-activated killer-sensitive and -resistant murine tumors.","authors":"R Maekawa,&nbsp;T Kitagawa,&nbsp;K Koizumi,&nbsp;K Sato,&nbsp;M Homma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The antitumor mechanism of recombinant human interleukin-2 (rIL-2) was studied using two murine tumor systems. Meth 8 tumor cells were easily lysed in vitro by rIL-2-activated killer (AK) cells, which mainly consisted of Thy1.2+, Lyt2.2+, L3T4- T cells, and asialo GM1+ natural killer (NK) cells; on the other hand, X5563 tumor cells were only slightly lysed in vitro by AK cells under the same conditions. One of these two tumors was inoculated i.d. into C3H/HeN mice and then rIL-2 (5 X 10(4) J.U./mouse/day) was repeatedly injected s.c. For AK-sensitive Meth 8-bearing mice, rIL-2 therapy starting 1 day after tumor inoculation was more effective for the growth than the therapy starting 7 days later and the therapeutic effect was abrogated by in vivo treatment with anti-asialo-GM1 serum. In contrast, for mice bearing AK-resistant X5563 tumor cells, delayed administration starting on day 7 or later was more beneficial than earlier administration on day 1 or 4. This treatment schedule resulted in complete tumor regression in a dose-dependent manner including significant inhibition of metastases in the spleen and/or lymph nodes. These therapeutic effects of rIL-2 on X5563 were not seen in T-depleted mice with anti-mouse thymocyte serum but were found in NK-depleted mice upon treatment with anti-asialo-GM1 serum. The results of these studies showed that the growth of AK-sensitive Meth 8 tumor was inhibited by AK cells, while the growth and metastases of AK-resistant X5563 tumor was inhibited by tumor-specific T cells, which were generated after tumor development and activated by rIL-2 therapy, rather than AK cells.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"676-90"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13742076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cell and interferon-gamma involvement in the adjuvant action of a detoxified endotoxin.","authors":"M A Tomai,&nbsp;A G Johnson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The adjuvant activities of a detoxified derivative of endotoxic lipopolysaccharides, isolated from the outer membrane of gram-negative bacteria, were evaluated in aging mice. This monophosphoryl lipid A (MPL) (Ribi) was capable of enhancing antibody production in vitro in splenic cultures from 2-3-month-old male Balb/c mice as well as cultures from 22-24-month-old Balb/c mice. Separation of spleen cells from MPL and phosphate-buffered saline-injected mice into adherent and nonadherent populations and subsequent mixing of populations and culture with antigen implicated an adherent cell as being involved in the enhancement of antibody formation induced by MPL. However, separation of normal spleen cells into purified populations of adherent cells, T-lymphocytes, and B-lymphocytes, followed by in vitro stimulation of the individual populations with MPL and subsequent transfer into cultures of normal spleen cells, revealed only the T cell as capable of transferring the enhancement of antibody formation. In addition, culture filtrates from MPL-stimulated T cells were able to enhance antibody production by spleen cell cultures from aging mice twofold above that of filtrates from unstimulated T cells. The enhancement of antibody formation induced by such filtrates and also by MPL in spleen cell cultures from young and aging mice was inhibited by a monoclonal antibody (MAb) to recombinant interferon-gamma (rIFN-gamma) as well as antiserum against IFN-alpha, -beta, and -gamma, but not by an antiserum to IFN-alpha/beta. Enhancement of antibody formation correlated well with an increase in interleukin-1 (IL-1) but not with an increase in IL-2 production. Addition of anti-asialo-GM1 MAb plus complement to the effective spleen populations did not diminish the adjuvant action.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"625-43"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13658058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effects of F1 and P1 fractions obtained from a Klebsiella pneumoniae glycoproteic extract (RU 41740) on polymorphonuclear leukocytes.","authors":"A el Abbouyi,&nbsp;J L Paul,&nbsp;M Roch-Arveiller,&nbsp;G Sarfati,&nbsp;J P Giroud,&nbsp;D Raichvarg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>RU 41740 is a glycoprotein extract from Klebsiella pneumoniae described as a macromolecular aggregation of a lipopolysaccharide (LPS)-associated protein (F1 fraction) and a glycoproteic complex (P1 fraction). The human polymorphonuclear (PMN) response was studied after incubation of the cells in the presence of RU 41740, F1 and P1 fractions, or F1-P1 complex. Oxidative metabolism was assessed by chemiluminescence, O2 consumption, O2- generation, and degranulation by beta-glucuronidase release. Results were compared to data obtained with a homologous LPS. RU 41740, F1 fraction, and F1-P1 complex increased the respiratory burst of PMNs stimulated by opsonized zymosan (OZ). N-formylmethionylleucylphenylalanine (fMLP), phorbol myristate acetate, or the calcium ionophore A23187. The beta-glucuronidase release was stimulated by the same compounds when OZ or fMLP were used as stimuli. These effects were dose-dependent. In contrast, P1 fraction was inactive. Addition of polymyxin B resulted in a profound inhibition of both the F1 fraction and LPS activities but only in a partial inhibition of RU 41740 effects. These results strengthen the hypothesis that different biochemical pathways are involved in the enhancement of stimulated neutrophil functions by RU 41740.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"656-64"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13700279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of anti-C5a antibodies on human polymorphonuclear leukocyte function: chemotaxis, chemiluminescence, and lysosomal enzyme release.","authors":"J R Hatherill,&nbsp;K E Stephens,&nbsp;K Nagao,&nbsp;A Ishizaka,&nbsp;L Wilmarth,&nbsp;J C Wang,&nbsp;T Deinhart,&nbsp;J W Larrick,&nbsp;T A Raffin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previous investigation has demonstrated that in vivo complement activation can produce acute lung injury. Complement component C5a has been implicated as a key factor in this damage. In addition, C5a is thought to play a central role in mediating polymorphonuclear leukocyte (PMN) function. Studies suggest that administering antibodies to C5a might play a role in attenuating lung injury in animal models of sepsis. To evaluate further the effects of anti-C5a antibodies, we compared the effects of anti-human C5a des-Arg monoclonal (MAb) and polyclonal (PAb) antibodies on PMN functions including chemotaxis, chemiluminescence, and lysosomal release. PMN chemotaxis was assayed in Boyden chambers using 0.5% zymosan-activated serum (ZAS) as a source of C5a and 0.5% normal human serum (NHS) as a control. PMN chemiluminescence was measured by scintillation counting using ZAS as a stimulant and NHS as control. In addition, the lysosomal marker enzyme beta-D-glucuronidase was spectrophotometrically determined to assess lysosomal release. The PMN chemotactic response to ZAS was completely abolished with MAb and PAb anti-C5a antibodies (p less than 0.01). Control antibodies had no effect on ZAS-stimulated chemotaxis. The anti-C5a MAb markedly inhibited PMN chemotaxis at concentrations ranging from 20 to 0.2 microgram/ml, and was approximately 30 times more potent than the PAb. ZAS-stimulated PMN chemiluminescence was markedly decreased in response to monoclonal antibodies to C5a. In contrast, the control antibody did not inhibit ZAS-stimulated PMN chemiluminescence. Anti-C5a antibodies also significantly attenuated the release of the lysosomal enzyme beta-D-glucuronidase from ZAS-stimulated PMN. Anti-C5a antibody treatment did not cause a significant lytic effect when incubated with PMN, as demonstrated by the absence of the cytoplasmic marker lactate dehydrogenase in the supernatant. These studies suggest that in states of complement activation, MAbs and PAbs may decrease PMN functions including chemotaxis, chemiluminescence, and lysosomal enzyme release.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"614-24"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13742074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretion of tumor necrosis factor during fetal and neonatal development of the mouse: ontogenic inflammation.","authors":"K Yamasu,&nbsp;H Onoe,&nbsp;G Soma,&nbsp;H Oshima,&nbsp;D Mizuno","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Inflammation plays an important role in homeostasis of the body. We therefore can assume that an inflammatory state occurs during ontogenesis of animals. To address this problem, we examined the ability of tumor necrosis factor (TNF), one of the inflammatory mediators, to be secreted by mouse cells during development. We cultured cells prepared from various parts of fetuses (10-19 days of gestation) and postnatal brains by collagenase digestion and assayed the secreted TNF activity by the L-929 cytotoxicity test. We found TNF activity by fetal cells without any stimulation. The spontaneous secretion of TNF was relatively high at around 13-15 days of gestation. The secretion was enhanced by lipopolysaccharide (LPS), showing that fetal cells are in an activated state for TNF secretion. These TNF activities were neutralized completely by rabbit anti-murine TNF antibody. Spontaneous and LPS-enhanced secretion by postnatal brain cells reached a peak around 7 days after birth, and thereafter declined rapidly. This time course was well correlated to the increase in the weight of brain. The producing cells were negative in macrophage marker surface antigen, and heterogeneous in relation to adherence and phagocytic activity, showing that TNF is secreted by various types of cells in the fetal body. These results suggest the presence of an inflammation-like state during ontogenesis. We consider that this \"ontogenic inflammation\" may be the prototype of inflammation, which can regulate homeostasis of the adult body.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"644-55"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13742075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice.","authors":"A L Barsoum,&nbsp;J H Coggin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A tumor/fetal associated antigen, termed oncofetal antigen (OFA), conserved in the tumor and fetal tissue of rodents and humans, was extracted from murine fibrosarcoma cells and tumors and was fractionated on an Ultrogel AcA34 gel filtration column. A monoclonal antibody 115 specific for the OFA identified three peaks of antigenic activity in the eluted fractions, designated fractions (Fr.) I, II, and III, in the molecular weight range of greater than 160, 90, and 44 kDa, respectively. Most of the activity resided in the high molecular weight fraction, Fr. I. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and gel scanning of Fr. I showed multiple bands, one of which, constituting about 5.6% of the total protein bands in Fr. I, was the 44 kDa oncofetal antigen, apparently present in this fraction in a soluble complex form. Lectin binding studies and isoelectric focusing showed that the 44 kDa OFA is a glycoprotein, whose pI is 6.8. Spleen and peritoneal exudate cells of BALB/c mice immunized with Fr. I protected naive syngeneic mice, in adoptive transfer experiments, from developing tumors when challenged with syngeneic fibrosarcoma tumor cells, MCA-1315. Also, immune spleen cells were cytotoxic to the tumor target cells, MCA-1315, in a 51Cr release assay at several different effector to target cell ratios. This is the first description of a conserved, true, oncofetal antigen capable of inducing tumor transplantation resistance in syngeneic rodents in a semipurified form.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 6","pages":"579-92"},"PeriodicalIF":0.0,"publicationDate":"1989-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13742073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous whole blood UltraPheresis procedure in patients with metastatic cancer.","authors":"M R Lentz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sixteen patients with metastatic cancer, each with bidirectionally measurable disease, were treated with a total of 24 membrane UltraPheresis procedures each to remove a low molecular weight (less than 150,000 daltons) plasma fraction. No other oncologic treatment was applied during the 2 months of study. The procedure was generally well tolerated, and no clinically significant adverse effects were observed from the procedure. A consistent tumor-specific inflammatory response was observed following the UltraPheresis procedure and was associated with lymphocytic infiltration of tumor and tumor necrosis that was demonstrated in those patients evaluable by repeat biopsy. In some patients, anergy was reversed and Karnofsky status improved. Six of the 16 patients had reduction of the sum of mean cross-sectional diameters of measureable lesions by 50% or more.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 5","pages":"511-27"},"PeriodicalIF":0.0,"publicationDate":"1989-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13933478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of various interleukins (IL-1, IL-2, and IL-3) on the in vitro radioprotection of bone marrow progenitors (CFU-GM and CFU-MEG).","authors":"V S Gallicchio,&nbsp;B C Hulette,&nbsp;M J Messino,&nbsp;C Gass,&nbsp;M W Bieschke,&nbsp;M A Doukas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Radiation exposure to various systems can result in the development of severe toxicity, known as the acute radiation syndrome, with hematopoietic tissues being acutely susceptible to radiation-induced injury. Usually it is the degree of hematopoietic toxicity that determines the feasibility of further tumor control doses of therapy. Therefore the development of agents capable of protecting hematopoietic tissues could have important clinical applications. The cytokine interleukin-1 (IL-1) has been demonstrated to be an effective agent capable of protecting hematopoietic tissues in vivo from the toxicity associated with radiation exposure. We report here the results of studies designed to further investigate the capability of various cytokines (IL-1 and interleukins-2 and -3) to protect bone marrow-derived hematopoietic progenitors [granulocyte-macrophage and megakaryocyte colony-forming units (CFU-GM and CFU-Meg)] from radiation exposure in vitro. Only IL-1 was effective in protecting CFU-GM and CFU-Meg from radiation-induced toxicity in the range of 1-10 U/ml; however, no protection was observed when the radiation dose was greater than 300 rad. The ability of IL-1 to block radiation-induced toxicity was negated in the presence of an antibody to IL-1. These studies provide further information on the effectiveness of IL-1 in protecting in vitro hematopoietic tissues from toxicity associated with radiation exposure.</p>","PeriodicalId":15063,"journal":{"name":"Journal of biological response modifiers","volume":"8 5","pages":"479-87"},"PeriodicalIF":0.0,"publicationDate":"1989-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13933479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}