Molecular analysis of HLA DRB1 and DQB1 in Italian patients with pemphigus vulgaris.
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HLA-DQ Antigens↗
Biomedical subjects
A Salerno
Publications and source records attributed to A Salerno.
Control mechanisms of cell-mediated reactions.
One of the most relevant aspects of tumor adoptive immunotherapy is provided by clinical trails on transfer of cytotoxic cells (LAK and TIL). However, LAK cell therapy is effective in a small number (16-22%) of only certain tumors, while therapy with TIL cells is efficient in about 40% of melanomas. Several possibilities have been raised to explain the low efficacy of cytotoxic cells in tumor therapy, amongst which are the poor immunogenicity of tumor and tumor-induced immunodepression. Furthermore, the possibility that cytotoxic cells do not reach the tumor site in adequate numbers has to be considered. We have developed an experimental system to study the ability of antigen-specific T cells to reach the target antigen in the tissues. The results obtained demonstrate that gamma delta cells and IL-4 are required to allow tissue localization of antigen-specific alpha beta cells, thus indicating that their ability to exert certain effect or functions requires cooperation by other cells types. These results may be relevant to the understanding of the mechanisms leading to localization of immunologically active cells at a tumor site.
Animals↗
Biocompatibility studies on glass ionomer cements by primary cultures of human osteoblasts.
Glass ionomer cements (GICs) are materials largely employed in the dental field that have been considered recently as cements in orthopaedic surgery for their proven osteogenic features. The aim of this study was to compare the response of cultured human osteoblastic cells to a number of commercial glass ionomer cements in order to provide indications useful for the further development of formulations that have potential for use as cements or implants in repair and replacement of bone tissue. The GICs tested were: Ketac-Fil Aplicap, lonocem lonocap 1,0, GC Fuji II, GC Fuji II LC and Vitremer 3M. Several features such as plating efficiency, adhesion and morphology of the cells were studied, as well as the only specific biochemical parameter of osteoblastic phenotype, namely osteocalcin production. In addition, the colonisation of materials by osteoblastic cells was verified by means of scanning electron microscopy. Altogether, the results obtained indicate that four of the five glass ionomer cements tested are biocompatible, showing vital cells adhering to the materials, proliferating and expressing the biochemical markers of osteoblastic phenotype, whereas Vitremer 3M, although currently employed in the dental field, exhibits a great cytotoxicity toward the cells. The adverse reaction of this GIC can be attributed to the leaching of at least two components of the polyacidic phase evidenced by protonic magnetic resonance analysis (PMR), namely 2-hydroxyethylmethacrylate (HEMA), and an unidentified acidic species. The addition of pure HEMA at the same concentrations found by means of PMR to cultures of osteoblastic cells resulted in a complete cell death. Our results also show that in vitro methods employing primary cultures of human cells specific to the implant sites of prostheses are appropriate and suitable tools for evaluating biocompatibility of materials. Furthermore, this kind of approach can provide indications useful in the design of novel materials as well as in improving the characteristics of the formulations already available.
Biocompatible Materials↗
Motor evoked potentials (MEPs): evaluation of the different types of responses in amyotrophic lateral sclerosis and primary lateral sclerosis.
We studied different motor evoked potential parameters: cortical threshold (CT), primary response (PR) latency and amplitude and central conduction time (CCT) at rest and after maximal voluntary contraction of the target muscles, silent period (SP) and late muscular responses (LMR) in 21 normal subjects 42- to 75-years old and compared the results to those of 17 patients with motor disease (10 amyotrophic lateral sclerosis, ALS and 7 primary lateral sclerosis (PLS). We report for the first time in patients affected by motor diseases, LMRs were similar to controls. We found abnormalities in both ALS and PLS: enhanced cortical threshold, reduced PR amplitude during maximal voluntary contraction of target muscles compared to rest and shorter SP. CCT was slightly different: in ALS it was normal or undetermined (because of lack of the PR), while it was normal, enhanced or undetermined in PLS. We conclude that except for LMR, additional parameters would be useful for studying motor diseases: CT (reflecting excitability of the central cells), PR amplitudes and SP (disclosing inhibitory pathway disturbances in pyramidal tract diseases).
Adult↗
Interhemispheric facilitation and inhibition studied in man with double magnetic stimulation.
Double magnetic stimulation was used to investigate the influence of a conditioning magnetic shock, applied to the hand motor area, on the size of the EMG response of the first dorsal interosseous (FDI) muscle elicited by magnetic test stimulation, applied to the same area of the opposite hemisphere, in 55 subjects unaffected by neurological disease. Both hemispheres were studied and compared at different intervals between shocks, ranging from 1-15 ms. With short intervals between shocks (1-5 ms), the EMG response to the target muscle of the test shock was increased (facilitation); it diminished after 6 ms (inhibition). Facilitatory effects started at 1-2 ms between shocks and lasted up to 5 ms between shocks. They were mainly present on one side; only 11/35 subjects tested from 1 to 5 ms between shocks had bilateral facilitatory effects. No significant differences between right and left hemispheres and sexes were noted. The conduction time to mediate facilitation between hemispheres was estimated at 8-9 ms. No facilitation occurred when the electrical test shock was conditioned by a magnetic shock, or when the magnetic test shock was conditioned by an electrical shock. We conclude that facilitation takes place at the cortical level since electrical stimulation is known to act on axons and magnetic stimulation on neurons. Facilitation did not occur when the magnetic conditioning coil was moved away from the motor area, suggesting that it requires pathways that link these areas, e.g. the corpus callosum. Facilitation was observed with muscles at rest; it disappeared when the FDI muscle was contracted. Inhibition occurred after 6 ms between shocks. It was noted in both hemispheres, in all subjects tested with no gender differences observed. The depth of inhibition increased with an increase in the interval between shocks. It clearly started at 6 ms between shocks in both hemispheres. The conduction time between hemispheres for inhibitory phenomena was estimated at 13 ms. We concluded that interhemispheric facilitatory and inhibitory phenomena are present in man, as suggested by experimental data in animals. For clinical purposes, we propose an interval of 4 ms between shocks to investigate facilitatory interhemispheric influences and 11 ms for inhibitory effects.
Adult↗
IL-5 enhances in vitro and in vivo antigen-specific IgA production in MHC genetically determined low IL-5 responder mice.
Lymphonode cells from BALB/k mice, but not from BALB/c mice, immunized with picryl chloride (PCl) produce IL-5 when stimulated with the specific antigen in vitro and this correlates with picryl-specific IgA levels in vivo, which are 6 to 10 times higher in BALB/k mice. B lymphocytes from BALB/k mice cultured with PCl-immune T cells from BALB/k produce in vivo anti-PCl-IgA, while B lymphocytes from BALB/c mice, cultured with T cells from BALB/c mice, fail to produce appreciable amounts of anti-PCl IgA, unless IL-5 is added to cultures. B lymphocytes from both strains of mice produce similar amounts of total IgA antibodies when stimulated in vitro with lipopolysaccharide. In vivo administration of IL-5 to BALB/c mice increases significantly PCl-specific IgA levels to those observed in BALB/k mice and a dose-response analysis reveals that 500 units of IL-5 was the minimal effective dose, although a small increase in PCl-specific IgA levels was observed with 100 units of IL-5. Total IgA levels were increased in both strains of mice following in vivo injection of IL-5, but no significant difference in the values was observed. Our results therefore indicate that IL-5 in vivo enhances antigen-specific IgA production in MHC-determined low IL-5 responder mice and suggest an explanation for IgA deficiency in humans.
Animals↗
Release of arachidonic acid metabolites by human fetal membranes: interrelationship between leukotriene B4 and prostaglandin E2.
The objective of this study was to ascertain whether human fetal membranes metabolize arachidonic acid preferentially through the lipoxygenase rather than the cyclooxygenase pathway before labor and whether an interaction between lipoxygenase and cyclooxygenase products is present in these tissues. Reflected fetal membranes were obtained from 8 healthy women at term gestation who were delivered by elective repeat cesarean section before the onset of labor. Tissues were cultured either in the presence or in the absence of the calcium ionophore A23187 for 60 minutes. Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were measured in culture medium by radioimmunoassays. Moreover, the effect of different concentrations of exogenously added LTB4 on PGE2 release was evaluated. The basal and stimulated output of LTB4 by tissues was significantly higher than that of PGE2. Addition of LTB4 significantly decreased PGE2 release by tissues. These findings suggest that in the above tissues: 1) the arachidonate lipoxygenase pathway is highly active before labor; 2) LTB4 might play a role in the regulation of PGE2 production.
Arachidonic Acid↗
Interleukin-2 in human amniotic fluid during pregnancy and parturition: implications for prostaglandin E2 release by fetal membranes.
The potential role of interleukin 2 (IL-2) in human pregnancy was investigated by evaluating the following. (1) The presence and concentrations of IL-2 in amniotic fluid (AF) in 24 women at 16-18 weeks' gestation (Group 1) and in 27 women at term pregnancy, either before the onset of labor (Group 2, n = 10) or during spontaneous active labor (Group 3, n = 17). (2) The production of IL-2 by fetal membranes at term gestation (n = 7). (3) The release of prostaglandin E2 (PGE2) by the above tissues after stimulation with IL-2 (n = 10) or phytohemagglutinin (PHA) (n = 8). Immunoreactive IL-2 was detected only in AF samples obtained from women of Groups 1 and 3; the higher concentration was found in Group 1 samples; IL-2 was not detected in AF samples from women of Group 2. Tissues did not release IL-2. Both IL-2 and PHA exerted a significant stimulatory effect on PGE2 release by tissues. IL-2 stimulated PGE2 release by chorion tissue, but not by amnion tissue. The following conclusions can be drawn: (a) AF IL-2 might play a role in the maternal-fetal immune relationship during early pregnancy and, perhaps, during labor; (b) fetal membranes would not seem to represent a source of AF IL-2 in the absence of labor; (3) IL-2 might influence arachidonic acid metabolism through the cyclooxygenase pathway in the chorion tissue.
Amniotic Fluid↗
Stimulation of macrophages with IFN gamma or TNF alpha shuts off the suppressive effect played by PGE2.
PGE2 has been shown to be able to interfere with various lymphocyte and macrophage functions, but its effects on macrophage activation are still unclear. In this study, carried out on peritoneal macrophages obtained from healthy, tumour-bearing and Corynebacterium parvum-treated mice, we demonstrated that PGE2 is involved in the down-regulation of macrophage activation, but it cannot exert its inhibiting effect when macrophages are further stimulated with activating cytokines, such as IFN gamma and TNF alpha. Our findings provide new insight into how macrophage tumoricidal activity may be induced and maintained even in presence of significant levels of PGE2.
Animals↗
A rapid and safe method to fix india ink on specimen resection margins.
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Carbon↗
Major histocompatibility complex control of the class of the immune response to the hapten trinitrophenyl.
This paper investigates major histocompatibility complex (MHC) regulation of the class of the immune response given in vitro and in vivo following immunization of the congenic BALB/k (H-2k) and BALB/c (H-2d) mice with the hapten trinitrophenyl (TNP). TNP-immune lymph node cells from BALB/k mice produced high levels of interferon-gamma (IFN-gamma), interleukin-5 (IL-5) and IL-2 when stimulated with TNP-antigen-presenting cells (APC) in vitro, while TNP-immune lymph node cells from BALB/c mice produced very low levels of these cytokines. No significant difference was found in antigen-specific production of IL-3, IL-4 and tumour necrosis factor-alpha (TNF-alpha). There was a strong correlation between the pattern of cytokine production in vitro and the secondary antibody production in vivo. Sera from BALB/k mice had anti-TNP IgG2a, IgG2b and IgG3 levels threefold greater, and anti-TNP IgA levels eightfold greater, than BALB/c mice. The level of specific IgG1 and IgE was only marginally raised in BALB/k mice. In contrast to these strain differences in cytokine and antibody production, there was no difference in two measures of cellular immunity: contact sensitivity in vivo and antigen-specific lymphocyte response in vitro. Our results suggest that there is a good correlation between the production of cytokines in vitro and antibody response in vivo, but not with measures of cellular immunity. Moreover, this MHC control of the class of the immune response to TNP does not fit into the T-helper type-1 (Th1)-Th2 paradigm.
Animals↗
Interleukin-4 is a critical cytokine in contact sensitivity.
This study demonstrates an essential role for interleukin-4 (IL-4) in the delayed hypersensitivity reaction, as illustrated by contact sensitivity (CS) to trinitrochlorobenzene (TNCB). Injection of mice with monoclonal antibody to IL-4, but not with control antibody, reduced CS after active immunization by 75%, as judged by ear swelling. The histological alterations of CS were also reduced. IL-4 was essential to the effector stage, as inhibition of its production or action blocked the passive transfer of CS. In particular, treatment of immune lymph node cells with antisense oligonucleotide to IL-4 inhibited the systemic transfer of CS. Transfer was also inhibited by monoclonal antibody to IL-4 given to the recipient. The present results indicate that IL-4 is an essential cytokine at the effector stage of the CS reaction.
Animals↗
Intraductal papillary-mucinous neoplasm of the pancreas. A clinicopathologic entity.
AIMS: The main clinicomorphologic findings from two new cases of intraductal papillary-mucinous neoplasm of the pancreas were analyzed and discussed. METHODS: Formalin-fixed pancreatic tissues from the more representative areas were routinely stained. An electron microscopic examination was performed in case 2 on glutaraldehyde-fixed tissue fragments. RESULTS: Both patients had a long history of symptoms that was suggestive of chronic pancreatitis. At endoscopic retrograde pancreatography a dilatation of the main duct was observed. Ultrasonography revealed cystic dilatations that were interpreted as pseudocysts. The patients underwent total pancreatectomy. The gross appearance showed no mass, but the pancreas was enlarged and diffusely hard. The cut surface showed micromacrocysts filled with soft friable tissue and mucus. Histological examination revealed diffuse neoplastic papillary proliferations within ectatic and cystically dilated ducts. The lesions exhibited varying grades of atypia and foci of in situ carcinoma. No clear evidence of invasion or lymph node metastases were observed. The nontumorous pancreas showed diffuse and multiple hyperplastic papillary changes in the ductal tree. CONCLUSION: The main clinicopathologic findings of intraductal papillary-mucinous neoplasm of the pancreas have been reported. Our study favors the hypothesis that chronic pancreatitis and/or ductal epithelial papillary hyperplasia may play a role in the pathogenesis of this tumor. We have emphasized the cystic appearance and mucinous features of this neoplasm, and so we suggest the use of the term intraductal papillary-mucinous neoplasm.
Cystadenoma, Mucinous↗
IL-4 is essential for the systemic transfer of delayed hypersensitivity by T cell lines. Role of gamma/delta cells.
Hapten (trinitrophenyl)-specific T cell lines were obtained by repeated stimulation of lymph node cells from immune mice with Ag in vitro. These T cell lines show phenotypic properties and a pattern of cytokine production typical of Th1 cells and consisted of more than 90% V beta 8.2+ T lymphocytes and 6 to 9% gamma/delta + T lymphocytes. The lines mediate a local passive transfer of DTH when injected at the site of Ag challenge but fail to mediate a systemic passive transfer of DTH when injected i.v. However, a successful systemic passive transfer of DTH was observed when IL-4 was given to recipient mice together with the T cell lines or when the T cell lines were incubated in vitro with IL-4. IL-4 enables systemic, specific passive transfer of DTH at a dose of 10 pg/ml in vitro and at a dose of 10 pg/mouse in vivo; it is effective when injected 4 h before cell transfer but not when given 1 to 5 days earlier. Cytofluorimetric analysis shows that the gamma/delta + cells and not the V beta 8.2+ cells of the line express IL-4R and a good systemic transfer of DTH is observed when gamma/delta + cells are incubated in vitro with IL-4 and then injected together with V beta 8.2+ cells into recipient mice. In contrast, injection of V beta 8.2+ cells treated with IL-4 together with gamma/delta + cells fails to transfer DTH. Overall, the present results show that IL-4 is an important mediator in the DTH reaction and that gamma/delta + cells are one of the targets of its action.
Animals↗
Induction of graft versus host disease in SCID mice by MRL/lpr cell transfer.
We have investigated the graft versus host (GvH) disease induced in immunodeficient SCID (H-2d) mice by intravenous (iv) or intraperitoneal (ip) transfer of either spleen or lymph node cells from autoimmune (MRL/lpr and MRL/++ mice, H-2k) and normal (CBA, H-2k) mice. Rapid and lethal GvH disease was observed when cells from MRL/lpr or MRL/++ were iv transferred into SCID mice, while spleen cells from nonautoimmune CBA donors were partially tolerized into SCID recipients and induced only lower levels of GvH reaction. No GvH reaction (complete tolerance) was observed when CBA lymph node cells were iv transferred into SCID recipients. In contrast, the ip injection of MRL/lpr or CBA spleen cells induces similar levels of GvH. The development of GvH disease in SCID recipients was due to the expansion of alloreactive CD8+ cells displaying significant cytotoxic activity against H-2d, but not against autologous targets. Also, a significant decrease of CD4/CD8 ratio was observed in the course of GvH caused by the iv transfer of cells from MRL/lpr mice. Altogether, these data support the hypothesis that lymphocytes from the MRL/lpr mice may escape tolerance in the GvH reaction.
Animals↗
[Value of a rapid method to determine muscle fiber density in amyotrophic lateral sclerosis].
We shortened single fiber electromyography examination by evaluating fiber density, jitter and block numbers in the 10th and the 20th different needle positions in the extensor digitorum communis. The results obtained in 15 normal subjects and 12 amyotrophic lateral sclerosis patients were comparated. There were no significant differences with the 10th and 20th needle positions in normal subjects or in patients. This method diminished patient discomfort and shortened the examination time.
Adult↗
Analysis of the adoptive transfer of delayed hypersensitivity and T cell repertoire in severe combined immunodeficiency mice reconstituted with human lymphocytes.
The functional capacity of human T cells to passively transfer delayed hypersensitivity (DH) was analysed in severe combined immunodeficiency (SCID) mice. The tissue distribution of human peripheral blood lymphocytes (PBL) was analysed by 51chromium labelling 1 and 24 h after intravenous cell injection. Labelled PBL from purified protein derivative (PPD)-positive healthy individuals mainly localize in the spleen, liver and lungs, with no arrival in the peripheral lymphoid organs and at the site of antigen challenge (footpad). According to such defective distribution, human PPD-immune cells failed to passively transfer PPD-specific DH to SCID recipients when cells were injected either intravenously or intraperitoneally (systemic transfer). On the contrary, PPD-immune cells were able to transfer DH to PPD when injected directly into the footpad (local transfer). Both memory (CD45RA-) and naive (CD45RA+) enriched subsets were equally able to transfer local DH. The long-term reconstitution of the human immune system in SCID mice was analysed after intraperitoneal PBL transfer (hu-PBL-Scid) by phenotypic analysis, immunoglobulin level, and human DNA detection. Moreover, the reconstitution of the V beta T cell receptor (TCR) repertoire in SCID mice was analysed by anchored polymerase chain reaction (PCR) showing that all the 22 V beta families were expressed in the spleen of hu-PBL-SCID mice. Moreover, scanner analysis of Southern blotting revealed the selective expansion of distinct V beta families (V beta 3, V beta 6, V beta 8, V beta 13.1, V beta 14, V beta 17), suggesting that human lymphocytes could recognize specific antigens or superantigens in the SCID environment.
Animals↗
[Somatosensory evoked potentials in amyotrophic lateral sclerosis and primary lateral sclerosis].
Somatosensory evoked potentials (SEPs) were studied in 21 cases of amyotrophic lateral sclerosis (ALS) and 7 cases of primary lateral sclerosis (PLS). Despite the lack of clinical sensory abnormalities, SEPs showed abnormalities in both diseases: lack or delay of some components. In ALS these abnormalities indicate widespread sensory disturbance. In PLS only, the Brodmann area 4 seems to be affected.
Adult↗