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A Bonomo

Publications and source records attributed to A Bonomo.

At least 19 recordsLinked to original sources
PubMed2005

Linking immunity and hematopoiesis by bone marrow T cell activity.

Two different levels of control for bone marrow hematopoiesis are believed to exist. On the one hand, normal blood cell distribution is believed to be maintained in healthy subjects by an "innate" hematopoietic activity, i.e., a basal intrinsic bone marrow activity. On the other hand, an "adaptive" hematopoietic state develops in response to stress-induced stimulation. This adaptive hematopoiesis targets specific lineage amplification depending on the nature of the stimuli. Unexpectedly, recent data have shown that what we call "normal hematopoiesis" is a stress-induced state maintained by activated bone marrow CD4+ T cells. This T cell population includes a large number of recently stimulated cells in normal mice whose priming requires the presence of the cognate antigens. In the absence of CD4+ T cells or their cognate antigens, hematopoiesis is maintained at low levels. In this review, we summarize current knowledge on T cell biology, which could explain how CD4+ T cells can help hematopoiesis, how they are primed in mice that were not intentionally immunized, and what maintains them activated in the bone marrow.

Animals↗
PubMed2005

Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.

Animals↗
PubMed2005

[Staging role of micrometastatic sentinel lymph nodes in breast cancer].

AIM: Axillary dissection may be avoided in patients with breast cancer and negative sentinel lymph node (SL); not all metastatic SL patients show metastasis on the remaining axillary lymph nodes. The purpose of this study was to evaluate the possible presence of metastases in the remaining axillary lymphatic glands, the so called not-SL, in patients with SL either macro- or micrometastatic, and to try to locate a subgroup of patients in which metastases are present only in SL. METHODS: A retrospective study was conducted in 91 patients who from March 2000 to June 2003 underwent a biopsy of SL and dissection of the axillary cavity (23 patients with micrometastatic SL and 68 with macrometastatic SL). A multivariate analysis evaluated the statistic association with not-SL metastases of almost 22 prognostic factors. RESULTS: Of the 68 patients affected by macrometastatic SL, 32 (47%) showed metastases of the not-SL; of the 23 patients with micrometastatic SL, 7 (30%) showed metastases of the not-SL. In the last 2 years, among all those patients with micrometastatic SL, the probability of disease at the not-SL reached the null percentage. During year 2000, 3 (50%) patients out of 6 with micrometastatic SL showed metastases at the not-SL; during years 2002/2003 no patients out of 8 with micrometastatic SL showed metastases at the not-SL. A multivariate analysis showed only 2 factors significantly associated to the metastatic not-SL: age (cut off 60 years) OR 4.6, P 0.003 and histological examination of the SL OR 2.8, P 0.003. CONCLUSIONS: The average frequency of disease of not-SL in patients with either micro- or macrometastatic SL is not so different than values observed in literature. The predictive disease value of the remaining axillary lymphatic glands of the micrometastatic SL reached the null percentage in the last 2 years, therefore at seems to depend on the operators experience in SL biopsy technique. Among patients with metastatic SL (micro and macro), it was not possible to detect a subgroup in which not-SL are not metastatic with reasonable certainty. Nevertheless, a multivariate analysis showed the histological factor of the SL, to be significantly associated to not-SL metastases, as well as to the age-factor.

Adult↗
PubMed2003

Bone marrow stroma inhibits proliferation and apoptosis in leukemic cells through gap junction-mediated cell communication.

Normal and leukemic blood cell progenitors depend upon the bone marrow (BM) stroma with which they communicate through soluble and membrane-anchored mediators, adhesive interactions and gap junctions (GJ). Regarding hematopoiesis, it is believed that it can be influenced by connexin expression, but the exact role of GJ in cell death and proliferation is not clear. Using flow cytometry, we monitored the division rate of leukemic cell lines, communicating and not communicating with stromal cell line through GJ. We found that GJ-coupled cells (i) did not proliferate; (ii) were kept in G0; and (iii) were protected from drug-induced apoptosis when compared to either total or uncoupled cell population. We conclude that GJ coupling between stroma and leukemic lymphoblasts prevents proliferation, keeping cells in a quiescent state, thus increasing their resistance to antimitotic drugs. Since GJ are particularly abundant in the sub-endosteal environment, which harbors blood stem cells, we also asked which cells within the normal human BM communicate with the stroma. Using a primary BM stroma cell culture, our results show that 80% of CD34+ progenitors communicate through GJ. We propose that blood cell progenitors might be retained in the low-cycling state by GJ-mediated communication with the hematopoietic stroma.

Antigens, CD34↗
PubMed2003

T-lymphocyte function from peripheral blood stem-cell donors is inhibited by activated granulocytes.

BACKGROUND: PBSC transplant provides 10 times more T cells than BMT However, the incidence and severity of acute GvHD is similar among recipients of both types of transplants. Studies in mouse models suggest that the similar clinical outcome in BMT and PBSCT is due to differences in the lymphokine profiles. METHODS: PBMC, PBMC from G-CSF mobilized donors (G-PBMC)and BM mononuclear cells (BM-MC) were analyzed by flow cytometry and ELISA to detect gamma-IFN and IL-4 production. Hematoxylin and eosin staining was used to identify morphology and annexin/propidium-iodide was used for apoptosis assays. RESULTS: We show decreased production of gamma-interferon (85%) and IL-4 (60%) in G-PBMC when compared with either PBMC or BM-MCT cells on ex vivo assays. Surprisingly, 85% of fresh G-PBMC is composed of low-density granulocytes (LDG), which undergo apoptosis after 48 h in culture. At this same time, gamma-IFN production from G-PBMC T cell was reverted. In vitro, G-CSF converts granulocytes into LDGs, able to inhibit T-cell function by H2O2 production, and not through immune-deviation towards a Th2-type phenotype. DISCUSSION: We show that the estimated numbers of Th1 and Th2 cells infused in BMT and PBSCT do not differ significantly. These findings are discussed with reference to the relatively low incidence of acute GvHD in PBSCT shown in the literature. We suggest that these results might depend on the high number of granulocytes and progenitors infused. The potential use of granulocytes as immunosupressive short-term therapy is now being investigated by our group using a mouse experimental model.

Annexin A5↗
PubMed2002

Serum levels of cobalt and chromium in a complex modular total hip arthroplasty system.

There is concern that modularity in a total hip arthroplasty system increases serum cobalt and chromium ion levels. This study measures the serum cobalt and chromium levels in patients with an Oxford Universal Hip (Corin, Cirencester, United Kingdom), which has a modular sliding mechanism; patients with a similarly manufactured hip with no sliding mechanism; and a control group. Loosening was excluded clinically and radiologically. Arthroplasty patients had statistically higher levels of serum cobalt and chromium than controls, but there was no significant difference in levels between the implanted groups.

Arthroplasty, Replacement, Hip↗
PubMed2001

Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity.

Programmed cell death by apoptosis of unnecessary or potentially harmful cells is clearly beneficial to multicellular organisms. Proper functioning of such a program demands that the removal of dying cells proceed without an inflammatory reaction. Phosphatidylserine (PS) is one of the ligands displayed by apoptotic cells that participates in their noninflammatory removal when recognized by neighboring phagocytes. PS ligation induces the release of transforming growth factor-beta (TGF-beta), an antiinflammatory cytokine that mediates the suppression of macrophage-mediated inflammation. In Hydra vulgaris, an organism that stands at the base of metazoan evolution, the selective advantage provided by apoptosis lies in the fact that Hydra can survive recycling apoptotic cells by phagocytosis. In unicellular organisms, it has been proposed that altruistic death benefits clonal populations of yeasts and trypanosomatids. Now we show that advantageous features of the apoptotic process can operate without death as the necessary outcome. Leishmania spp are able to evade the killing activity of phagocytes and establish themselves as obligate intracellular parasites. Amastigotes, responsible for disease propagation, similar to apoptotic cells, inhibit macrophage activity by exposing PS. Exposed PS participates in amastigote internalization. Recognition of this moiety by macrophages induces TGF-beta secretion and IL-10 synthesis, inhibits NO production, and increases susceptibility to intracellular leishmanial growth.

Animals↗
PubMed1999

Extramedullar B lymphopoiesis in liver schistosomal granulomas: presence of the early stages and inhibition of the full B cell differentiation.

Inflammatory granulomatous reactions in liver elicited by schistosomal infection have been shown to function as active extramedullar myelopoietic sites, producing potentially all the myeloid lineages. We have now addressed the question of the extramedullar B lymphopoiesis in these sites. We have shown the presence of early B cell precursors (pro-B cells) in the granulomas by immunophenotyping. Their total number in the liver was equivalent to the pro-B cells in the bone marrow of one femur. In agreement with their phenotype, the RT-PCR analysis showed that these cells expressed RAG-1 and lambda5 genes. However, the conversion of the pro-B to pre-B cells was not observed and no clonogenic B cell precursors could be detected in semi-solid cultures stimulated by IL-7. The granulomatous stroma was shown to produce IL-7 and express c-kit, and was able to sustain the full B lymphopoiesis in vitro. Conversely, the granuloma supernatant was shown to inhibit actively the development of B lymphocytes. We conclude that the granuloma environment elicits homing and proliferation of totipotent hematopoietic precursors, and that it is permissive for early commitment to the B cell lineage, but the full extramedullar production of B cell is abrogated by soluble factors produced inside the granulomas.

Animals↗
PubMed1999

Does arthritis progress in the retained compartments after 'Oxford' medial unicompartmental arthroplasty? A clinical and radiological study with a minimum ten-year follow-up.

We determined the outcome of 56 'Oxford' unicompartmental replacements performed for anteromedial osteoarthritis of the knee between 1982 and 1987. Of these, 24 were in patients who had died without revision, one was lost to follow-up and two had been revised. Of the remaining 29 knees, 26 were examined clinically and radiologically, two were only examined clinically and one patient was contacted by telephone. The mean age of the patients was 80.3 years. At a mean follow-up of 11.4 years (10 to 14) the measurements of the knee score, range of movement and degree of deformity were not significantly different from those made one to two years after operation, except that the range of flexion had improved. Comparison of fluoroscopically-controlled radiographs at a similar interval of time showed no change in the appearance of the lateral compartments. The retained articular cartilage continued to function for ten or more years which suggests that anteromedial osteoarthritis may be considered as a focal disorder of the knee. This justifies continued efforts to develop methods of treatment which preserve intact joint structures.

Aged↗
PubMed1997

Involvement of laminin and its receptor in abrogation of heart graft rejection by autoreactive T cells from Trypanosoma cruzi-infected mice.

Extracellular matrix ligands and receptors have been identified as determining in vivo lymphocyte positioning and activation, including effector functions in alloreactive responses. Herein we evaluated the involvement of laminin and its receptor, the very late antigen 6 (VLA-6) integrin, in CD4+ T cell-dependent autoreactivity, using a transplantation model for the autoimmune myocarditis occurring in mice chronically infected with Trypanosoma cruzi. Previous work showed that syngeneic mouse hearts grafted in the ears of chronic chagasic recipients were rejected through a CD4+ T cell-dependent mechanism. Rejection also occurred when cells from chagasic animals were transferred adjacent to hearts transplanted into naive recipients. Here, we observed the formation of a thick laminin network during rejection, with donor-derived CD4+ T cells concentrated in the laminin-rich areas. Most importantly, anti-laminin as well as anti-laminin receptor Ab inhibited the rejection of syngeneic hearts by T cells from chagasic animals. Our results suggest that interaction of the VLA-6 molecule with laminin is involved in triggering the antimyocardial autoreactive process by driving the influx of CD4+ T cells to the heart. They also support the concept that an Ag-specific T cell response, even an autoreactive one, can be modulated by in vivo interactions involving extracellular matrix ligands and receptors. In this regard, our study represents, to our knowledge, the first in vivo evidence for laminin-mediated T cell echotaxis, with simultaneous experimental demonstration of ligand and receptor involvement. Lastly, our findings indicate that treatment with anti-VLA-6 Abs can be effective in suppressing autoimmune disease activity.

Animals↗
PubMed1997

[Cystic dilatation of the choledochus associated with stenosis of the hepatic duct bifurcation. An analysis of a clinical case].

The authors report a case of cystic dilatation of the choledochus associated with narrow stenosis at the confluence of the left and right hepatic ducts which was found to be inflammatory on histological examination. This pathology is becoming an increasingly more commonplace clinical finding. The case reported here is particularly interesting owing to the onset of the disease and the way in which it was treated. An attempt was made to treat the patient using a simple operation which was to the least radical possible. The authors take this opportunity of reviewing the literature on the subject.

Aged↗
PubMed1997

[Access to the rectum via a posterior route and via a combined abdominal-posterior route: when and why].

The authors report their experience of the posterior rectal access route. They used this route to operate 7 patients with rectal carcinoma during the period February 1989-October 1994; 3 patients were affected by villous adenoma, 3 by adenocarcinoma, and 1 by pelvic recidivation. Of the 3 patients suffering from adenocarcinoma, two underwent palliative treatment owing to their poor general conditions and the systemic nature of the base pathology, consisting in the exeresis of the tumour using a posterior route. The third patient was treated using a combined abdominal-posterior route; the site of the tumour and the presence of a narrow pelvis would in fact have made an "ultra low" front resection highly risky, whereas coloanal anastomosis (pull through) might have jeopardized efficacious anal continence. On the basis of their experience the authors indicate the posterior access route as a therapeutic possibility in the treatment of medium-low rectal tumours at an early or very advanced stage. The posterior approach is only justified in other forms if combined with laparotomic access. An oncologically correct operation is therefore guaranteed in full respect of sphincteric function.

Adenocarcinoma↗
PubMed1996

[Hepatic amebiasis. Apropos of two cases].

The authors report 2 cases of amebic hepatic abscess, through to their observation with a little interval of time one from another and both coming from the same small town. Transmission modalities, the diagnostic approach and the therapeutic possibilities are discussed on the basis of personal experience.

Adult↗
PubMed1995

Pathogenesis of post-thymectomy autoimmunity. Role of syngeneic MLR-reactive T cells.

Thymectomy of 3-day-old mice results in the development of multi-organ-specific autoimmune diseases. The disease process is mediated by CD4+ T cells and is characterized by an inflammatory infiltrate in the affected organ(s) and the presence of autoantibodies. Our analysis of the phenotype of the CD4+ T cells that remain in the 3-day thymectomized animal revealed that the majority (approximately 80%) of the CD4+ lymph node cells express an activated (MEL-14low) phenotype and a smaller percentage expressed the T cell activation Ag CD69 and IL-2R alpha-chain. Thymectomized animals also had an increase in the frequency of mitogen-induced CD4+ IL-4 producers and significantly higher levels of total serum IgG. Functional studies demonstrated that lymph node T cells from 3-day thymectomized mice had an enhanced response in the syngeneic MLR and appeared to preferentially respond to syngeneic dendritic cells. To determine whether the syngeneic MLR-reactive T cells were involved in the pathogenesis of the organ-specific disease, we developed a model that mimicked the 3dTx model by grafting neonatal thymi to adult nu/nu recipients followed by removal of the thymus graft on day 3 or 4. When compared with mice transplanted with an untreated thymus, nu/nu mice transplanted with adult APC-containing thymi demonstrated a decrease in the incidence and severity of gastritis, a marked decrease in the titer of anti-parietal cell Ab, and a decrease in total serum IgG. Thus, intrathymic tolerization to complexes of self-peptides and MHC class II on adult APC prevents organ-specific autoimmune disease.

Animals↗
PubMed1995

Post-thymectomy autoimmunity: abnormal T-cell homeostasis.

Thymectomy of 3-day-old mice induces organ-specific autoimmune disease, which is characterized by the presence of autoantibodies and T-cell infiltrates in the affected organs. Here, Adriana Bonomo and colleagues propose a new model for the pathogenesis of this syndrome, which integrates many of the homeostatic mechanisms of the immune system, including central and peripheral tolerance, T-cell maturation and exportation from the thymus, as well as lymphocyte recirculation and homing.

Animals↗
PubMed1995

[Malignant tumors of the pancreas and periampullary area. Our experience].

The authors analyse and evaluate the clinical records of 45 patients treated in the last 4 years for pancreatic cancer and neoplasm of the bilioduodenapancreatic area, comparing the results with data available in the literature. In the group of patients treated with resection (12 cases), postoperative morbidity and mortality were respectively 28% and 6%, and three-years survival was 22%. The authors discuss particularly about reconstruction ways after duodenopancreatectomy, showing good results after reconstruction by Y loop sec. Roux and pancreato-jejunal anastomosis.

Adenocarcinoma↗
PubMed1994

Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.

Animals↗