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Objectives: The aim of this study was to analyse the long-term result after reconstruction of the medial orbital wall with a flexible, biodegradable material (Ethisorb ®). Materials and methods: During a period of almost 8 years, 31 patients with a medial orbital wall fracture were analysed retrospectively. Inclusion criteria were patients with a maximum size fracture of the orbital medial wall measuring 1.5-2 cm. Exophthalmos, enophthalmos, bulbus motility, diplopia and skin sensation were investigated over a period of 6 months. In all patients, the medial orbital wall was reconstructed with Ethisorb ® patches. Results: No significant intraoperative complications were detected. No postoperative infection, abscess or seroma was found in any of the patients receiving an Ethisorb ® patch. Conclusions: The advantage of the semiflexibility of the Ethisorb ® patch is that it supplies an anatomically correct fit to the orbital medial wall but does not require fixation by screws or the use of sutures. Clinical relevance: The low rate of reported bulbus motility disturbance, diplopia, exophthalmos and enophthalmos demonstrates acceptable results after medial orbital wall reconstruction using the Ethisorb ® patch. [ABSTRACT FROM AUTHOR]

Lymphoid tissue from newborn rabbits was examined using fluorochrome conjugated goat antisera to rabbit γ, μ and α heavy chain and mixed light chain. Unimmunizcd newborn rabbits examined at intervals up to 20 days of age revealed a very low background of approximately one in 105 cells which stained with either the anti-μ, anti-γ or anti-L chain reagents. Newborn rabbits, immunized intrapcritoncally on the day of birth with S. paralyphi B (4, 5, 12:b), showed a 1000-fold increase in the number of stained cells; μ heavy chain containing cells were found 16 hours after immunization, and γ heavy chain containing cells were found 20 hours after immunization in the rabbit spleen tissue. The numbers of μ containing cells and γ containing cells were approximately equal at 5 days of age in tile immunized groups. No α heavy chain containing cells were found in any of tile rabbits studied. All cells which stained with the anti-μ or γ heavy chain reagent were also stained with the anti-light chain reagent. The cellular response of the immunized newborn rabbits could be inhibited by passive antibody to S. paralyphi B, either given at the time of immunization, or passively acquired from the doc. Specificity of inhibition was indicated by the failure of sheep red blood cells (SRBG) stroma to be inhibited in animals so suppressed. The range of cellular morphology of the γ chain containing and the μ chain containing cells was indistinguishable. The earliest cell to be stained with either anti-γ or anti-μ was a large blast-like cell with a thin rim of cytoplasm and a large nucleus. A full range of forms between this and typical plasma cells appeared later in each case. These findings present a paradox since γG antibody to this antigen does not appear in the serum of stroll animals following γM class in the usual sequence characteristic of adult animals. Possible explanations of this paradox arc explored. [ABSTRACT FROM AUTHOR]

The effect of age on the proliferative response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) was examined using peripheral blood lymphocytes from 185 adults. TPA-induced DNA synthesis measured by cellular 3H-thymidine incorporation was found, like the responses of cells activated by PHA and Con A, to markedly diminish with advancing age. The presence of indomethacin (1 μ/ml) or Ro 20-5720(10 μg/ml) in TPA activated cell cultures, unlike PHA stimulated cultures, did not result in augmentation of ³H-thymidine incorporation by cells from elderly individuals. These results demonstrate that prostaglandin synthesizing suppressor cells are not responsible for the age-related depression of cellular immune function observed in TPA activated cells and confirm the observation that decreased production and/or utilization of soluble mediators, such as IL-2, may account for the diminished mitogen responsiveness of lymphocytes from elderly individuals. [ABSTRACT FROM AUTHOR]

The effect of age on the in vitro generation of immunoglobulin-secreting cells in pokeweed mitogen-stimulated cultures was examined using a staphylococcal protein A plaque assay. Although there was no statistically significant decrease with age in the numbers of plaque-forming cells, subjects whose cells failed to produce immunoglobulin were four times more common amongst individuals over 55 years of age. Simultaneously-measured I and B lymphocyte numbers, 3H-thymidine incorporation by mitogen-stimulated cultures, and serum immunoglobulins were comparable in both the young and the aged. [ABSTRACT FROM AUTHOR]

Groups of 6-week-old female C57B1/6 mice were fed a normal diet with recommended levels of all vitamins Dr a vitamin-deficient (VD) diet containing half of the recommended level of each vitamin. At different time periods (1-11 weeks) after the initiation of diets, basal natural killer (NK) activity, interleukin-2 (IL-2) and concanavalin A (Con A)-induced cytotoxic activity, Con A-induced IL-2 production and levels of allospecific cytotoxic T cell activity generated in a mixed lymphocyte culture (MLC), were studied in spleen cells derived from control and VD mice. Results indicated that: (i) spleen NK activity remained normal until 2 weeks after the initiation of VD diet, fell steeply to tow levels at the 4 and 5 week time points and remained depressed thereafter; (ii) IL-2- and Con A-induced levels of cytotoxic activity in spleen cells derived from VD mice declined at 4 weeks alter the institution of VD diet, and then remained low throughout the study; (iii) the capacity of spleen cells from VD mice to generate IL-2 in response to Con A and cytotoxic T cells in response to allogeneic spleen cells, was normal at 1 and 4 weeks alter initiation of the VD diet and was markedly depressed at the 6 and 9 week time points. These results suggest that partial combined deficiencies of dietary vitamins strongly influence assays of immune function. [ABSTRACT FROM AUTHOR]

Our previous work has shown that antibody-coated mouse spleen cells express enhanced cytotoxic activity against some Fc-receptor-bearing target tumour cells by a mechanism which appears to be similar to an antibody-dependent cell-mediated cytotoxicity (ADCC) reaction with reversed polarity of the antibody bridge (R-ADCC). In this report we have shown that (i) the levels of basal natural killer (NK), ADCC and R-ADCC cytotoxic activities in mouse spleen cells are strongly correlated with each other, (b) simultaneous induction of ADCC and R-ADCC reactions does not result in an additive cytotoxic response, and (iii) YAC cells which do not bear Fc receptors and are highly sensitive to lysis by NK cells, can specifically and competitively inhibit the ADCC and R-ADCC reactions. These results suggest that the R-ADCC reaction may be mediated by the same effector cell population as mediates NK and ADCC reactions against tumour target cells. [ABSTRACT FROM AUTHOR]

Concanavalin A (Con A)-induced cytotoxic activity, interferon (IFN) and interleukin-2 (IL-2) levels in cultures of spleen cells from young (2-3 months) and old (22-24 months) C578L/6 female mice were studied. Con A-activated spleen cells from old mice attained significantly higher cytotoxic activity compared with activated spleen cells from young mice. Activated spleen cells from old and young mice showed differences in their ability to lyse different types of target cells. Both could lyse P 815 cells, neither could lyse K562 cells, and only activated cells from old mice could lyse EL-4 cells. Cytotoxic spleen cells from the old mice were more sensitive to anti-asialo-GM-l and anti-Lyt-2.2 plus complement (C) treatment. While levels of IL-2 produced by spleen cells from young mice were higher, the addition of exogenous IL-2 had no effect on cytotoxic activity of the spleen cells from old mice. Exogenous IL-2, however, could lower cytotoxic activity of Con A-activated spleen cells from young mice. Activated spleen cells from old mice generated higher levels of IFN-γ while the addition of an anti-IFN-γ antibody boosted the level of cytotoxicity by Con A-activated spleen cells from young mice. These results suggest that IFN-γ may act as a feedback inhibitory signal regulating the levels of cytotoxicity induced in spleen cells from young mice in response to Con A. The cytotoxic activity generated in Con A-activated spleen cells from old mice reflects a defect in this feed-back regulation. [ABSTRACT FROM AUTHOR]

PurposeTo assess the combined diagnostic power of frequency-doubling technique (FDT)-perimetry and retinal nerve fibre layer (RNFL) thickness measurements with spectral domain optical coherence tomography (SDOCT).MethodsThe study included 330 experienced participants in five age-related groups: 77 'preperimetric' open-angle glaucoma (OAG) patients, 52 'early' OAG, 50 'moderate' OAG, 54 ocular hypertensivepatients, and 97 healthy subjects. For glaucoma assessment in all subjects conventional perimetry, evaluation of fundus photographs, FDT-perimetry and RNFL thickness measurement with SDOCT was done. Glaucomatous visual field defects were classified using the Glaucoma Staging System. FDT evaluation used a published method with casewise calculation of an 'FDT-score', including all missed localized probability levels. SDOCT evaluation used mean RNFL thickness and a new individual SDOCT-score considering normal confidence limits in 32 sectors of a peripapillary circular scan. To examine the joined value of both methods a combined score was introduced. Significance of the difference between Receiver-operating-characteristic (ROC) curves was calculated for a specificity of 96%.ResultsSensitivity in the preperimetric glaucoma group was 44% for SDOCT-score, 25% for FDT-score, and 44% for combined score, in the early glaucoma group 83, 81, and 89%, respectively, and in the moderate glaucoma group 94, 94, and 98%, respectively, all at a specificity of 96%. ROC performance of the newly developed combined score is significantly above single ROC curves of FDT-score in preperimetric and early OAG and above RNFL thickness in moderate OAG.ConclusionCombination of function and morphology by using the FDT-score and the SDOCT-score performs equal or even better than each single method alone. [ABSTRACT FROM AUTHOR]

Sorted OKT4+ cells treated with pokeweed mitogen (PWM) and subsequently X-irradiated were used as a source of helper T cells to examine human T and B cell function. PWM-induced immunoprotein synthesis by human peripheral blood lymphocytes was the model used to study cellular interactions. PWM was shown to induce helper T cell function which caused non-PWM treated B cells to secrete immunoglobulin. PBL from certain individuals could not be induced by PWM to secrete Ig therefore allogeneic co-cultures of helper T cells and B cells were examined to define the defective cell population. Ig synthesis allogeneic cultures of T and B cells was always greater than that observed in autologous cultures when cells from responders were assayed. However, when allogenic cultures were initiated using B cells from a responder and PWM treated T cells from a non-responder and examined for Ig synthesis, the B cell responses were markedly lower than seen in the autologous responder cultures. In addition, PWM activated helper T cells from a responder induced a significantly higher Ig synthesis by B cells from a non-responder. These observations indicate that PBL from individuals who do not respond in a PWM driven Ig synthesis assay have relatively normal B cell function but are deficient in helper T cell function. [ABSTRACT FROM AUTHOR]

Previous studies have shown that exogenous IL-2 does not correct the reduction in phytohaemagglutinin (PHA)-induced proliferation of lymphocytes from HIV-1 infected (HIV+) individuals. We investigated the mechanism of this reduction to determine if reduced expression of the complete IL-2 receptor (IL-2R) was responsible. In a series of experiments, PH A-stimulated lymphocytes from a total of 89 HIV- and 93 HIV+ homosexual men from the Baltimore Multicentre AIDS Cohort Study (MACS) were studied to determine the expression of messages for the α and β subunits of the IL-2R, the binding of 125I-IL-2 to high affinity IL-2R, and the effect of IL-2 on cell proliferation. Compared to HIV- donors, PHA-stimulated lymphocytes from most HIV+ donors demonstrated (i) a reduction in high affinity IL-2R expression that correlated with the reduction in the IL-2-induced proliferative response; and (ii) a reduction in expression of both IL-2R α- and jβ-chain mRNA which may be responsible for decreased high affinity IL-2R expression. However, lymphocytes from some HIV+ individuals had borderline low IL-2-induced proliferation despite normal or elevated expression of high affinity IL-2R. These results suggest that decreased expression of IL-2R may account, at least in part, for the lower proliferative response of cells from HIV+ donors. [ABSTRACT FROM AUTHOR]

High affinity interleukin 2 receptors (HA-IL-2R) on mitogen-or antigen-stimulated T cells have been shown to efficiently bind interleukin 2 (IL-2) and to transduce the activation signal(s) that facilitate proliferation. This study was initiated to determine whether the impaired proliferative response of T cells from elderly individuals can be attributed to the defective expression of HA-IL-2R. While cells from both young and old individuals had statistically insignificant differences in the number of HA-IL-2R per membrane IL-2R-positive cell and these receptors displayed similar binding affinities with 125-IL-2, there were consistently fewer cells and fewer cells expressing HA-IL-2R in the cell cultures from elderly individuals. The magnitude of the age-associated impairment in cell proliferation was decreased, but remained present, when Percoll fractionated lymphoblasts, as compared to peripheral blood lymphocytes (PBL), were cultured in the presence of exogenous interleukin 2 (IL-2). The results demonstrate that a significantly larger percentage of lymphocytes from elderly individuals do not respond to mitogenic stimulation and, probably due to stimulus stress, die in culture. As a consequence there are fewer functionally competent cells expressing the HA-IL-2R in cultures from elderly individuals, which in turn contributes to the age-related defect in the lymphocyte proliferative response. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells mediate host defense against infections and are regulated by interleukin 2 (IL-2) and other factors. We studied NK cell function in burn patients using a 51Cr release assay with K562 target cells. We found that peripheral blood lymphocytes from burn patients had depressed NK activity (target cell lysis = 22.0 ± 3.1% vs 39.8 ± 3.2% in healthy volunteers, P < 0.001) and also a lower response to IL-2 (28.9 ± 3.8% vs 53.2 ± 4.3%, P < 0.001). Thirteen burn patients were randomly assigned lo receive either standard therapy or 5 days of intravenous polymyxin B in addition fo standard therapy. After 2 weeks, the patients not receiving polymyxin B had a significant decline in peripheral blood NK activity (P < 0.01) and response to IL-2 (P < 0.05), white no decline in NK cell activity was seen in patients who received polymyxin B. Sera from burn patients was found to suppress the NK activity of lymphocytes from healthy adults by 5-75%. After using affinity chromatography to remove endotoxin, the sera from burn patients no longer suppressed NK cell activity. Circulating endotoxin appears to be involved in the suppression of NK activity in burn patients. [ABSTRACT FROM AUTHOR]

Current models of T cell activation implicate increases in intracellular free Ca2+ concentration and activation of the Ca2+ and phospholipid dependent enzyme protein kinase C (PKC) as important early events leading to interieukin 2 (IL-2) production, interleukin 2 receptor (IL-2R) expression, and subsequent cell proliferation. The present study examined the age-related defect in T cell proliferation to determine if the signals that activate PKC and increase intracytosolic free Ca2+ concentration might be defective. Using phorbol myristate acetate (PMA), which directly activates PKC, and Ca2+ ionophore A23187, which increases intracellular cytoplasmic free Ca2+ concentration, the induction of IL-2 secretion, IL-2R expression and cell proliferation were studied. The results demonstrate that following stimulation with PMA and A23187, purified T cells from elderly subjects demonstrate low levels of IL-2 production, IL-2R expression and cell proliferation. Exogenous purified human IL-2 did not fully correct the low proliferative responses of T cells from old donors, however, did markedly boost the response. While it appears that the inability of T cells to express IL-2 Rand respond to IL- 2, along with a lower endogenous IL-2 production are limiting factors in cell proliferation, the inability of PMA and A23187 to correct this defect suggests that the early phases of signal transduction per se are probably not a primary cause of the immunodeficiency seen in ageing. [ABSTRACT FROM AUTHOR]

Human peripheral blood T lymphocytes were treated with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) activity, and with the calcium ionophore A23187. The resulting accumulation of specific mRNA for interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R), as well as IL-2 secretion and membrane IL-2R expression were examined. At low concentrations (0.1 μM), A23187 synergized maximally with PMA to induce proliferation, to increase IL-2R mRNA levels and the expression of membrane IL-2R, and to produce a low but sufficient accumulation of IL-2 mRNA and IL-2 secretion. A high concentration of A23187 (1.0 μM) did not show any synergism for the accumulation of IL-2R mRNA, membrane IL-2R expression and inhibited the proliferation of PMA co-stimulated T cells. It did, however, induce maximum accumulation of IL-2 mRNA and IL-2 secretion. [ABSTRACT FROM AUTHOR]

Four specific interleukin-2 (IL-2) surface binding proteins can be detected by covalent cross-linking of [125I]IL-2 to rat spleen cells that have been activated with various stimuli including concanavalin A (Con A), phytohaemagglutinin (PHA), calcium ionophore, and phorbol dibutyrate (PDB) with or without calcium ionophore. These four cross-linked proteins could not be demonstrated in either unstimulated T cells or in activated T cells when binding was performed in the presence of a 20-100- fold excess of unlabelled IL-2. The molecular weights of the four cross-linked proteins, after subtraction of the molecular weight contribution of IL-2 are: 53,000,70,000,90,000 and 118,000. The 53,000 MW protein was identified as the rat 11-2 receptor (IL-2R) 2-chain by immune precipitation. Additionally, results suggest that the rat LL-2R α-chain is tightly complexed to both the 118,000 and 90,000 MW IL-2 binding proteins. Purification of surface labelled proteins from activated cells using IL-2 affinity chromatography yields four proteins with similar molecular weight to those identified by cross-linking plus an additional non-ligand cross-linked protein of 46,000 MW. The 46,000 MW band may be a non-binding associated protein since it was not seen following [125I]IL-2 binding cross- linking. Tryptic digests and two-dimensional separation of the affinity-isolated proteins indicate that unique peptide maps are generated for the 46,000. 53,000 and 70,000 MW proteins and excludes the possibility that the bands identified by cross-linking represents cross-linking of multiple ligands to the 53,000 MW subunit. However, the 90,000 and 118,000 MW bands yield peptide maps that closely resemble each other suggesting that these binding proteins may be related. These results suggest that at least four IL-2 surface binding proteins may constitute the rat IL-2R system. [ABSTRACT FROM AUTHOR]

Although, major histocompatibility complex (MHC) class H antigen expression in allografts is thoroughly studied, regulation of the genes for these antigens is not fully understood. The graft-specific MHC class II genes are potentially important in determining the immunogenicity of graft but their detection in a mixed-cell `population such as in the allograft would require unambiguous differentiation of graft-specific class II expression from those in host lymphoid cells. With an oligonucleotide probe that specifically hybridizes to I-Ab mRNA from He2k haplotype mice, we have studied I-A gene expression in cardiac allografts heterotopically transplanted from B10.Br (H2k) to B10.D2 (H-22) mice. Normal B10.Br hearts do not have appreciable I-Ab transcripts as determined with this probe, but 4 days after allografting, a substantial increase in I-Abk messenger RNA (mRNA) content was noted in the allografted hearts which persisted for the next 2 days and then decreased concomitant with destruction of the heart. The increase in I-Abk mRNA preceded the expression of surface lak antigens on dendritic and endothelial cells in the allograft. These data indicate increased transcription of the 1-Ab gene in cells of graft origin suggesting that transcriptional regulation is the initial mechanism for expression of class II genes in allografts. The sustained rise in grail-specific class 11 mRNA also seen in these allografts suggests that increased mRNA stability may be another mechanism for the increased density of class II antigens in allografts undergoing rejection. [ABSTRACT FROM AUTHOR]