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Biomedical subjects

M Nuti

Publications and source records attributed to M Nuti.

At least 19 recordsLinked to original sources
PubMed2006

Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short- and long-term therapeutic management of non-reconstructable lower critical limb ischemia?

AIM: The aim of this study was to evaluate the capacity of transcutaneous partial pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to pharmacological treatment in short- and long-term follow-up of unreconstructable critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic and therapeutic algorithm able to define the possibility of prostanoid therapy in unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs) considered unreconstructable after peripheral angiography and with a history of type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3 weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non-reconstructable CLI treated with Iloprost divided patients into 2 groups: early responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who underwent a second cycle of Iloprost within a few months of the first, TGM further divided the patients into another subgroup of late responders (LR) with TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after pharmacological treatment failure, should undergo eventual surgical re-timing and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS: In the short-term follow-up of CLI, a marked reduction in supine/dependent TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot proved to be significant predictors of major amputation risk. In the long-term follow-up period, TGM showed that, in ER and in LR, the favourable effect of pharmacological therapy observed in the first 6 months will disappear over the next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid therapy repeated every year. In NR treated with surgical and/or alternative therapies who did not undergo major amputations, prolonged instrumental TGM will provide a constant evaluation of metabolic parameters, thus providing the possibility to save the limb with additional pharmacological therapy.

Aged↗
PubMed2003

Modulation of blood circulating immune cells by radiofrequency tumor ablation.

Tumor ablation by radiofrequency (RFA) is an appealing therapeutical strategy for the treatment of liver tumors (hepatocarcinoma and metastatic lesions) to be used as valid alternative to the surgical resection that often is appropriate and feasible in only a minority of patients. RFA induces the localised and controlled disruption of the tumor by heating the tissue causing its coagulative necrosis. Such therapy results as a pathogenic "noxa" for the body, inducing a strong inflammatory response. We wanted to ascertain whether the inflammatory response induced by RFA was similar in patients with hepatocarcinoma and in patients with liver metastasis. We considered body temperature, leucocyte counts at different time points as inflammatory parameters. We observed that RFA treatment produced the inflammatory systemic effects as expected (fever, increase of neutrophils) only in the patients with liver metastasis, while no such effect could be seen in the HCC patients. On the other hand the circulating monocytes increased after RFA in both groups of patients. These preliminary results suggest that RFA tratment can exert different effects on the immune system depending the etiopathogenesis of the treated neoplastic liver lesions.

Body Temperature↗
PubMed2002

Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease.

BACKGROUND: It is unclear whether the extent of duodenal gastric metaplasia is due to Helicobacter pylori and/or acid. AIMS: To investigate the role of Helicobacter pylori eradication in the regression of duodenal gastric metaplasia in patients with duodenal ulcer maintained in acid suppression conditions. METHODS: . Duodenal (anterior, superior inferior walls of first part of duodenum) and gastric antrum biopsies were obtained from 44 Helicobacter pylori positive duodenal ulcer patients. Helicobacter pylori infection was diagnosed by rapid urease test, histology and 13C-Urea Breath Test. Patients were treated with 20 mg omeprazole tid associated with 250 mg clarithromycin and 500 mg amoxycillin four times daily for 10 days and maintained with 20 mg omeprazole daily for 18 weeks. Control endoscopies were performed at 6 and 18 weeks after beginning treatment. RESULTS: Duodenal gastric metaplasia regression was observed in all (32/32) patients in whom Helicobacter pylori was eradicated, but in only 3 out of 6 patients in whom eradication was not achieved (p<0. 001). CONCLUSIONS: . The present results suggest that Helicobacter pylori eradication associated with prolonged acid suppression may represent a good therapeutic strategy to achieve duodenal gastric metaplasia regression and highlight the combined role of acid and Helicobacter pylori in the pathogenesis of duodenal gastric metaplasia.

Adult↗
PubMed2001

Effects of granulocyte-colony-stimulating factor and granulocyte/macrophage-colony-stimulating factor administration on T cell proliferation and phagocyte cell-surface molecules during hematopoietic reconstitution after autologous peripheral blood progenitor cell transplantation.

Thirty-four ovarian and breast cancer patients received autologous peripheral blood progenitor cell transplantation after high-dose myeloablative chemotherapy and either granulocyte-colony-stimulating factor (G-CSF) or granulocyte/macrophage-colony-stimulating fictor (GM-CSF) in the immediate post-transplant period. The recovery of T cell functionality was monitored by a three-color flow-cytometric approach using carboxyfluorescein diacetate succinimidyl ester, a probe the fluorescence intensity of which halves at each round of cell replication, in conjunction with CD3 and CD25 monoclonal antibodies. There was no significant difference between the two treatments on days 12, 20, and 40, T cell proliferation always being considerably lower than that of control cultures from healthy donors. At day 80, a significantly higher proportion of mitogen-stimulated T cells from GM-CSF-treated patients expressed interleukin-2 receptor, and a higher proportion of these T cells were actively proliferating. This phenomenon did not reflect any difference in the relative proportion of various lymphocyte subsets (T cells, CD4 and CD8+ T cells, CD45RA+ and CD45RO- T cells, and natural killer cells). At the end of follow-up (1-1.5 years) T cell proliferation had returned to values typically observed in healthy individuals in both groups of patients. Soon after transplantation (day 12), neutrophils from G-CSF-treated patients had a more elevated Fcgamma receptor I density and monocytes from GM-CSF-treated patients had a more elevated Fcgamma receptor II and MHC class II molecules density. The up-modulation of Fcgamma receptor II was maintained until day 40. Thus, administering G-CSF and GM-CSF in the post-transplant period affects T lymphocyte proliferation and phagocyte membrane molecules differently.

Adult↗
PubMed2001

The role of growth factor administration and T-cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G-CSF and GM-CSF.

BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival. RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G-CSF and GM-CSF series. Conversely, significantly higher T-cell counts were observed in G-CSF-treated patients during the early and late posttransplant follow-up. Patients who received G-CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G-CSF-treated patients encourages the use of G-CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM-CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT.

Adult↗
PubMed2000

Transfected human dendritic cells to induce antitumor immunity.

Dendritic cells are professional antigen-presenting cells able to prime naive T lymphocytes and regulate steadily the delicate balance between tolerance and activation during the immune response. In past years several reports have shown that genetically engineered dendritic cells (DCs) can be a powerful tool for inducing an antigen-specific immune response. The use of such modified antigen-presenting cells is a real working hypothesis in preclinical studies and in clinical vaccination approaches for cancer treatment. The definition of optimal transfection conditions for preserving DC survival and functionality is necessary to design a correct immunotherapeutic protocol. Different lipid-based transfection compounds were studied for their effects on DC survival, phenotype and functional properties. All the transfection procedures were able to select DCs with a higher expression of activation and costimulatory molecules (ie MHCII-DR, CD83, CD86, CD25) than the untreated DCs. However, only two compounds (LipofectAMINE PLUS and FuGENE 6), preserved or even increased the immunopotency of DCs as antigen-presenting cells. These protocols were applied to modify DCs in order to express an epithelial tumor-associated antigen, MUC1, and such cells were able to induce in vitro a specific immune response in healthy donors.

Cancer Vaccines↗
PubMed1999

Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads.

The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3 weeks. B cell culture supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.

Adult↗
PubMed1996

Human antibodies against the polymorphic epithelial mucin in ovarian cancer patients recognise a novel sequence in the tandem repeat region.

The humoral immune response to the polymorphic epithelial mucin (PEM) was studied by characterising the reactivity of human antibodies generated by EBV-immortalised B-cells from tumour-draining lymph nodes of ovarian cancer patients. All the human antibodies, selected in ELISA for their reactivity to the protein tandem core repeat sequence, reacted with PEM-expressing tumour cells. Aberrant glycosylation of the peptide core of the PEM molecule in cancer cells leads to the exposure of peptide epitopes that can be considered tumour specific. The epitope mapping of six human antibodies revealed that only one of them contained the PDTR sequence, shown to be the immunodominant epitope in the mouse. Four of the six human antibodies recognised a novel common immunogenic sequence (APPAH) in the tandem repeats. The binding of these human antibodies did not appear to be modulated by the length of the carbohydrate side chains, as shown by O-glycosylation inhibition studies. These results indicate that distinct sequences within the tandem repeat of PEM are target for a humoral immune response in humans. The presence of antibodies directed against different epitopes within the same antigenic region may modulate the antigen presentation process and the ongoing immune response. This data may help in clarifying the mechanisms of the immune response to PEM in cancer patients for the development of PEM-based immunotherapy.

Antibodies, Neoplasm↗
PubMed1993

Human B-cell immune response to the polymorphic epithelial mucin.

Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor-draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients.

Adult↗
PubMed1993

Infections in an Alpine environment: antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia burgdorferi in defined Italian populations.

From 1987 to 1991, a seroepidemiologic survey for antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia was conducted in selected Italian population groups. In the mountainous areas of northeastern Italy, the prevalence of antibody to hantaviruses, as detected by indirect immunofluorescent antibody (IFA) assay, was 7.1%, 4.8%, 4.3%, and 4% in 265 forestry workers, 82 rangers, 395 farmers, and 75 hunters, respectively. Among 299 Alpine soldiers, the prevalence was lower (0.7%). Of those with Hantaan antibody, the reactivity pattern using Hantaan, Puumala, and Fojnica viruses suggested a prevalence of antibody to Hantaan virus, with titers reaching levels of 128. The presence of leptospiral antibodies (by microagglutination test), which included the prevalence of antibodies to Leptospira icterohaemorrhagiae, L. bratislava, and L. saxkoening serotypes, was observed in 10-12% of the farmers and forestry workers in these Alpine mountain regions. Only a few sporadic clinical cases of leptospirosis have been reported from these regions. Antibodies to Borrelia burgdorferi (by IFA) were observed in 19% of the rangers and forestry workers, with lower values in farmers (10%) and hunters (8%). These data suggest the presence of a large number of asymptomatic infections with B. burgdorferi and the leptospires in the densely wooded areas of the Alpine Italian regions. Furthermore, the recent identification of a case of Hantaan acute nephropathy in a man living in the mountainous northeastern area of Italy confirms the presence of hantavirus in the Italian Alpine zones, especially those near the Slovenian border.

Adult↗
PubMed1993

Sample preparation for bivariate flow cytometric analysis of breast tumor specimens.

The availability of monoclonal antibodies (MAbs) raised against functional or phenotypic cell markers can improve the suitability of flow cytometry (FCM) in assessing and validating prognostic parameters of human neoplasia. The major problems encountered in this type of study, when performed on solid tumors, are the recovery of a large and representative number of tumor cells and the possibility of performing a DNA analysis on antigen-selected populations. A panel of MAbs was chosen on the basis of the recognized membrane antigens important to the biologic characterization of human breast cancer cell populations. The possibility of performing bivariate FCM analysis of cell surface antigens and DNA content was investigated on 4 breast tumor cell lines and 10 fresh breast biopsies. Different fixations and tumor disaggregation procedures were considered. The results indicate that ethanol fixation is the most effective procedure for performing biparametric FCM analysis and that a combined enzymatic-mechanical disaggregation procedure applied on breast tumor specimens allows great recovery of intact cells without affecting antigen detection or DNA distribution.

Antibodies, Monoclonal↗
PubMed1992

Seroprevalence of antibodies to hantaviruses and leptospires in selected Italian population groups.

A study of hantaviral and leptospiral antibodies in selected population groups was performed. Among high risk subjects in the Rome area, Hantaan antibody was found in mammalogists (10%) and dialysis patients (6%), while none of the trappers, oarsmen, river policemen and firemen studied tested positive for antibodies to hantaviruses. In occupationally-exposed subjects (farmers, rangers, lumbermen, hunters) from rural and densely forested areas of northern Italian regions, the prevalence of Hantaan antibody ranged from 3.3% to 8.8%. In the positive cases the comparative antibody titration using different hantaviruses showed a predominance of Hantaan virus (titer 1:128) compared to Puumala virus (titer 1:32); no reactivity was observed with Seoul or Prospect Hill viruses. In Rome, leptospiral antibodies were found in trappers (21%) and oarsmen (5%) at a titer of 1:50 or more, with a predominance for the L. icterohaemorrhagiae serotype (85%). In the Alpine areas the leptospiral antibody prevalence was 12% and L. icterohaemorrhagiae and L. bratislava were the predominant serotypes. The presence of hantavirus infections, suspected after the first epidemiological survey conducted in central Italy, is now supported by the new data obtained in northern Italian regions. Furthermore, the recent observation of one case of Hemorrhagic Fever with Renal Syndrome (HFRS) in the Udine area, not far from the Yugoslavian border, strongly confirms the presence of one or more hantaviruses in Italy.

Adult↗
PubMed1992

Immunohistochemical analysis of the distribution of a breast tumor associated antigen recognized by a monoclonal antibody.

A new monoclonal antibody (MoAb), MM 1-80, recognizing a tumor associated epitope of a breast high molecular weight mucin molecule was tested, using the avidin biotin immunoperoxidase method on normal and pathological mammary tissues. The normal mammary ducts and lobules were negative. Fibroadenomas showed a strong intracytoplasmic staining. In apocrine metaplasia, adenosis, and papillomatosis, scattered cells showed intracytoplasmic, luminal border or secretion reactivity. In lobular and ductal hyperplasia the cells showed intracytoplasmic immunoreactivity which, however, became more intense and homogeneous in atypical lesions, i.e. lobular and ductal in-situ carcinomas. The infiltrating carcinomas of different histotype expressed positivity on 98% of the cases (113/115) and axillary metastatic lymph nodes were always positive (20/20). The MoAb was tested on 175 human neoplasias of different origin which were in the majority of the cases negative with the exception of adenocarcinomas of the lung, ovary and bladder. MM1-80 appears to react preferentially with mammary cells undergoing hyperplastic, metaplastic and neoplastic processes. The 1-80 epitope distribution is different in these lesions starting with a predominant luminal expression in benign lesions and becoming strong and cytoplasmic in the malignant breast cell.

Adult↗
PubMed1992

N-methylformamide effects on cell proliferation and antigenic pattern in HT-29 colon carcinoma cell line.

The effects of the differentiating agent N-methylformamide (NMF) on cell proliferation and antigenic pattern of HT-29 colon carcinoma cells have been investigated. The cell line was cultured in the presence, or absence, of 1% NMF and tested for the above mentioned characteristics, both in vitro and after injection into nude mice. The percentage of cells in the various cell cycle compartments was estimated by flow cytometry. The presentation on the cell surface of molecules such as tumour associated antigens (TAAs), HLA class I molecules and epidermal growth factor receptor (EGF-R) was analysed by ELISA, flow cytometry and immunohistochemistry. Results demonstrate that NMF impairs HT-29 cell proliferation with a remarkable accumulation in the G0/G1 phases, as well as inducing a modification of the membrane antigenic pattern. The presence of NMF in the culture medium decreases the TAAs and EGF-R whereas HLA antigen maintains the same level of positivity in the two cell lines. These alterations are consistent with a different behaviour in vivo of the tumours originated from NMF treated and untreated cells. Tumours derived from NMF treated cells show a delay in the appearance and low levels of immunodetectable carcinoembryonic antigen (CEA) molecules.

Animals↗