摘要:

SummaryThe effects of endotoxin treatment on host metabolism in tumour‐bearing investigated. Metabolism in control rats (non‐tumour‐bearing) was slightly altered by endotoxin treatment, whereas in tumour‐bearing rats a number of biochemical parameters that were intially perturbed by the presence of the tumour had returned to normal at 48 h post‐treatment. The beneficial effects included increased blood glucose and insulin concentrations, and decreased ketone body, triglyceride and lactate concentrations. Potentially non‐beneficial effects of endotoxin observed in both tumour‐bearing and control rats included decreased plasma cholesterol, and increased plasma phosphate, potassium and alkaline phosphatase levels.Endotoxin caused haemorrhaging in the encapsulated tumour, and this was associated with histological evidence of endorhelial damage, red cell infiltration into surrounding tumour tissue and a marked decrease in cell viability. Thein vivouptake of glucose by the tumour, measured by 2‐deoxy [U‐14C]glucose uptake, was decreased by 96% following endotoxin treatment, and this was associated with a two‐fold increase in glucose uptake by muscle. It is concluded that endotoxin treatment has major effects on cell viability and the integrity of vasculature in the tumour, which limits glucose uptake by the tumour and thereby decreases the energy and substrate requirements of the tumour, thus benefiting the host. It is suggested that tumour cytotoxicity and intra‐tumour haemorrhage are the result of endotoxin stimulating cytokine release from macrophages that are already activated by the presence of the tumour. While the effects of endotoxin on metabolism in tumour‐bearing rats appeared to be primarily the result of anti‐tumour activity, other findings, particularly the raised plasma alkaline phosphatase activity that was observed in endotoxin‐treated control and tumourbearing rats, indicate possible side effects that may need to be considered in any treatment strategy.

ISSN:0004-945X    

DOI:10.1038/icb.1992.1

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryNinety patients with rheumatic heart disease and 50 age‐ and sex‐matched healthy human volunteers representing a North Indian population were typed for the B cell alloantigen D8/17 using a monoclonal antibody and a single step immunofluorescence technique. This alloantigen was expressed in 66.44% patients with RHD as compared with 14% of the normal population. A high relative risk (RR = 11.13) indicated a strong association of D8/17 B cell alloantigen with rheumatic heart disease. Increase in the frequency of the marker was observed with increasing age up to the fifth decade (40–49 years) in these patients. However, the frequency of this alloantigen, in the present study, in North Indian patients with rheumatic heart disease is lower than that reported in the American population.

ISSN:0004-945X    

DOI:10.1038/icb.1992.2

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe supernatants of peripheral blood lymphocytes cultured in interleukin‐2 (IL‐2) for 4 days contained tumour necrosis factor (TNF) and interleukin‐1 (IL‐1). Addition of cisplatin (CP) or FK‐565 to these cultures increased the level of both of these cytokines in culture supernatants. Furthermore, when the LAK cells induced by culture with IL‐2 in the presence or absence of CP/FK‐565 were co‐cultured with tumour cells, the production of these cytokines was significantly enhanced. The level of enhancement depended on the ratio of LAK cells to tumour cells used and the length of coincubation of the two cell types. Culture supernatants of LAK cells and LAK cells stimulated by tumour cells were also cytotoxic to MCF‐7 and U937 cells in 72 h cytotoxic assay, and antibodies specific for TNF and IL‐1 inhibited the supernatant‐mediated cytotoxicity. These results suggest that, in addition to the up‐regulation of IL‐2‐induced LAK activity, treatment of PBL with CP/FK‐565 leads to enhanced production of various cytokines with potential antitumour and immunoregulatory activity.

ISSN:0004-945X    

DOI:10.1038/icb.1992.3

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThein vitroantileishmanial activity of sodium stibogluconate (SSG) and pentamidine in peritoneal macrophages from three different groups of animals (i.e. normal,Leishmania donovaniinfected and drug‐treated BALB/c mice) is reported. Peritoneal macrophages were extracted from all these animals and infectedin vitrowithL. donovanipromastigotes. After 24 h, the infected macrophages (with amastigotes) were exposed to various concentrations of SSG (10–90 μg/mL) and pentamidine (0.1–5.0 μg/mL). Thein vitroinfection could he cured readily with 80 μg/mL of SSG and 4 μg/mL of pentamidine in macrophages from normal animals. But even higher dosages of these drugs addedin vitrocould not reduce the amastigote loads in macrophages from infected animals. In contrast, incubationin vitroof infected macrophages with very low dosages of these drugs (40 μg/mL of SSG and 1.0μ/mL of pentamidine) could eliminate the parasites present within macrophages obtained from drug‐treated animals. This was probably because the macrophages from drug‐treated animals tackled the parasites themselves by their microbicidal mechanisms and thein vitroinfection was tackled by the drugin vitro.This implies that a well‐developed specific immunity in leishmaniasis helps in the antileishmanial activity of these drugs.

ISSN:0004-945X    

DOI:10.1038/icb.1992.4

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryLymphocyte and macrophage/dendritic cell populations in the oral cavity of the rat were studied by immunohistochemistry. Furthermore, the reactivity of the oral mucosa towards antigen and its position in the mucosal immune system was investigated by staining antibody‐forming cells and comparing serum and saliva antibody titres. Although numerous lymphocytes and non‐lymphoid cells were present in the oral mucosa, organized lymphoid tissue could not be found. The majority of the lymphocytes are T cells, particularly of the T‐helper phenotype. Macrophages were found only in the connective tissue, whereas dendritic cells also occurred in the epithelium. The possible functions of the cells in the different sites of the oral mucosa are discussed. Antibody‐forming cells were mainly detected in the draining superficial and posterior cervical lymph nodes and in the submandibular glands. The roles of the various compartments of the oral mucosal immune system are discussed with particular reference to the epithelium and connective tissue as induction sites, the draining lymph nodes as sites of proliferation and differentiation, and the submandibular glands as effector sites.

ISSN:0004-945X    

DOI:10.1038/icb.1992.5

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryCell‐mediated immunity is thought to be important in the resistance of chickens to infection by coccidia, and it has been demonstrated that sporozoites ofEimeria tenellaare very sensitive to superoxide ions. Therefore an investigation into the cellular responses in naive specific pathogenfree and hyperimmune birds was carried out with particular attention to their ability to produce reactive derivatives of oxygen. Leucocytes were isolated from the blood, spleen and caecal mucosa of chickens infected withE. tenellaand assessed for their ability to release H2O2‐ Leucocytes obtained from the blood and spleen of hyperimmune birds 1 day after challenge showed an elevated ability to produce reactive oxygen intermediates. In contrast, the ability of leucocytes from naive chickens to produce these molecules was transiently depressed after challenge. Prior to challenge, mucosal leucocytes from immune chickens were also able to release heightened levels of H2O2when compared with cells from naive chickens.

ISSN:0004-945X    

DOI:10.1038/icb.1992.6

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThere is convincing evidence for the imposition of self‐tolerance by means of the clonal deletion of self‐reactive T cells within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post‐thymically. To test this, we have used transgenic technology to direct expression of a‘non‐self gene, H‐2Kb, to the insulin‐producing β cells of the pancreas in mice. These‘RIP‐Kb’transgenic mice were specifically tolerant of H‐2Kb‐bearing skin grafts. To test the fate of potentially reactive H‐2Kb‐specific T cells in these tolerant mice, the RIP‐Kbmice were mated to a second series of transgenic mice with rearranged T cell receptor (TCR) genes encoding an H‐2Kb‐specific TCR to produce‘double transgenic’offspring. The TCR was detectable by a clonotype‐specific antibody. Although there was some evidence of intrathymic deletion of those T cells that expressed the highest density of the H‐2Kb‐specific TCR, lower density cells were present in the periphery. These may have been either indifferent to the H‐2Kbmolecule expressed on the p cells or functionally silenced by it. Further experiments are planned to determine which of these two situations exists.

ISSN:0004-945X    

DOI:10.1038/icb.1992.7

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryConstitutive lymphokine production by cells isolated from mice injected with keyhole limpet haemocyanin (KLH) or from mice undergoing an acute graftvshost reaction (GVHR) was very low, but could be markedly increased by T cell receptor (TCR) ligation. This suggested thatin vivolevels of lymphokine production are much lower than those induced byin vitrostimulation. Serum lymphokine titres were consistent with this possibility, and analysis of lymphokine mRNA levels using S1‐nuclease protection demonstrated thatin vitro‐stimulated cells from normal, KLH and GVHR mice all had markedly increased levels of lymphokine transcripts relative to levels foundin vivo.A novel method combining limiting dilution analysis with polymerase chain reaction amplification of cDNA was developed that showed that these differences in levels of lymphokine production were due at least in part to differences in the frequencies of lymphokine mRNA‐containing cells. Studies of the means by which differential lymphokine production is achieved demonstrated that CD4+, CD8+and cytotoxic T lymphocyte (CTL) clones all express a common, restricted set of lymphokines in response to a definedin vitrostimulus, but that individualin vivoprimed cells can express at least seven distinct patterns of lymphokine production.

ISSN:0004-945X    

DOI:10.1038/icb.1992.8

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryHuman adenovirases can cause persistent infections in man. The strategies of C type adenoviruses (types Ad2 and Ad5) to evade immune recognition are many, but all involve single early genetic regions (E3). Gene(s) within E3 have been shown to allow the adenovirus to avert cytokine‐mediated apoptosis. Furthermore, the E3 region controls the cytotoxic T cell epitope (a major histocompatibility complex [MHC] class I molecule with an adenovirus‐derived peptide) on the cell surface of infected cells. On the one hand the E3 gene product 19 kDa can bind to nascent class I MHC in the endoplasmic reticulum and thus prevent its transport to the cell surface, and on the other hand the E3 region down‐regulates the Ela gene product, the immunodominant cytotoxic T cell determinant.

ISSN:0004-945X    

DOI:10.1038/icb.1992.9

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryMutant group C adenoviruses defective in expression of the E3 transcription unit were found to overexpress E1a proteins relative to wild‐type adenoviruses. This result suggests that one or more proteins encoded in the E3 region (present in wild‐type viruses) down‐regulate E1a expression. This interpretation was confirmed by transfection experiments in which a plasmid expressing the E3 region reduced expression of E1a in 293 cells. Experiments to examine the molecular basis of this down‐regulation of E1a suggest that E3 protein products interfere with the translation of viral mRNA molecules.

ISSN:0004-945X    

DOI:10.1038/icb.1992.10

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY