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Biomedical subjects

M Bestagno

Publications and source records attributed to M Bestagno.

16 recordsLinked to original sources

A motion correction algorithm for an image realignment programme useful for sequential radionuclide renography.

The correction of organ movements in sequential radionuclide renography was done using an iterative algorithm that, by means of a set of rectangular regions of interest (ROIs), did not require any anatomical marker or manual elaboration of frames. The realignment programme here proposed is quite independent of the spatial and temporal distribution of activity and analyses the rotational movement in a simplified but reliable way. The position of the object inside a frame is evaluated by choosing the best ROI in a set of ROIs shifted 1 pixel around the central one. Statistical tests have to be ful-filled by the algorithm in order to activate the realignment procedure. Validation of the algorithm was done for different acquisition set-ups and organ movements. Results, summarized in Table 1, show that in about 90% of the simulated experiments the algorithm is able to correct the movements of the object with a maximum error less or equal to 1 pixel limit. The usefulness of the realignment programme was demonstrated with sequential radionuclide renography as a typical clinical application. The algorithm-corrected curves of a 1-year-old patient were completely different from those obtained without a motion correction procedure. The algorithm may be applicable also to other types of scintigraphic examinations, besides functional imaging in which the realignment of frames of the dynamic sequence was an intrinsic demand.

Algorithms

Monoclonal antibodies to human DNA topoisomerase I and the two isoforms of DNA topoisomerase II: 170- and 180-kDa isozymes.

Several monoclonal antibodies of different isotypes specific to human DNA topoisomerase I, to 170- and 180-kDa DNA topoisomerase II isozymes, were produced and characterized. The specificity of monoclonal antibodies was confirmed by comparison with polyclonal antibodies by Western blot, by immunoprecipitation of enzyme activity, and by immunoprecipitation of DNA topoisomerases with characterized polyclonal antisera. Morphological studies performed by immunofluorescence indicate that the three groups of monoclonal antibodies (MoAbs) stain the nucleus with characteristic patterns, which can be compared with those obtained with polyclonal antibodies. In particular the MoAbs to the 100-kDa DNA topoisomerase I stain the nucleolus and the nucleoplasm; the MoAbs to 170- and 180-kDa DNA topoisomerase II give completely distinct intranuclear patterns: those to the 170-kDa protein stain mainly the nucleoplasm, whereas those to the 180-kDa protein stain only the nucleolus. The two DNA topoisomerase II isozymes clearly exhibit fluctuations in their expression during cell growth: the 170-kDa isozyme is more abundant during the logarithmic phase of growth, while the 180-kDa isozyme is mainly present during the plateau phase of growth.

Antibodies, Monoclonal

Treatment of advanced neuroblastoma with I-131 meta-iodobenzylguanidine.

From February 1986 to December 1988, 31 children with advanced pretreated neuroblastoma were treated with 131-I meta-Iodobenzylguanidine (131-MIBG). Thirteen children had been resistant to first-line therapy, three had suffered a local relapse, and fourteen had suffered a disseminated relapse without over bone marrow infiltration. One child was treated initially because of resistance to first-line therapy, and subsequently for a local relapse. A total of 72 courses of 131-MIBG was administered, with doses ranging from 2.8 to 6.0 GBq (median, 3.7 GBq). One child received five courses, two four courses, 13 three courses, four two courses, and 12 one course of 131-MIBG. The most common toxic effect was thrombocytopenia, with a platelet level of less than 50,000/cmm occurring after 19 of 60 evaluable courses. A leukocyte count less than 1000/cmm was seen only once. There were six major responses (two complete) lasting 4 to 9 months, and two minor responses lasting longer than 38 and 44 months. Responses were seen more commonly in children whose only lesion was a residual primary tumor and in children who had not been pretreated who experienced disseminated relapse. Further studies of the role of 131-I meta-Iodobenzylguanidine in treatment of neuroblastoma are needed.

3-Iodobenzylguanidine

Synthetic and natural factors promoting production of murine and human monoclonal antibodies.

Human endothelial culture supernatant (HECS) contains factor(s) which promote the growth and the stability of hybridoma cells, and in these respects is superior to the commonly used feeder cells. In particular: HECS increases the recovery of hybridomas after fusion as compared to that in the presence of feeder cells; HECS can substitute feeder cells supporting the growth of hybridomas at the single-cell level under limiting dilution conditions; HECS prolongs the stability of human-mouse hybridomas producing human immunoglobulins (Ig). The active principle which is present in HECS can be different from IL-6. Furthermore the effects of a polyamine derivative, carboxyethyl gamma-aminobutyric acid (CEGABA), were studied on the growth of hybridomas and Epstein-Barr Virus-transformed cell lines. CEGABA enhances the growth of hybridomas through all the steps of hybridoma technology and induces the formation of a large number of EBV-transformed lymphocytes, when added to the culture medium immediately after EBV infection. However, CEGABA shows only a moderate effect on the stability of EBV-transformed cell lines over time, and does not effect the growth of stabilized cell lines. It is possible that CEGABA acts on cells other than EBV-transformed lymphocytes (in fact, after EBV infection all types of mononuclear cells from the blood are present in the culture) and indirectly promotes the growth of EBV-transformed lymphocytes.

Animals

Therapeutic possibilities of 131I-MIBG in metastatic carcinoid tumors--preliminary report.

The poor results of traditional therapy in advanced carcinoid tumors and the well-proven uptake of 131I-MIBG shown by some of these tumors induced us to attempt a radiometabolic approach. We selected for the treatment 5 patients (3 men and 2 women) who showed progression of disease, a fairly good uptake of 131I-MIBG with severe related symptoms, and a poor response to traditional therapy. A cumulative radioactivity of 5.5-29.6 GBq was given. Acute side effects after 131I-MIBG administration or late radiation-induced damages were not observed. Symptoms increased during the first 2-4 weeks in 2 patients: in one of these relief was achieved with drugs. Results concerning objective remission of the disease were unsatisfactory. In contrast, definite improvement of symptoms was shown in 2 of 5 patients, resulting in a better quality of life.

3-Iodobenzylguanidine

Antibodies from patients with rheumatoid arthritis and systemic lupus erythematosus recognize different epitopes of a single heterogeneous nuclear RNP core protein. Possible role of cross-reacting antikeratin antibodies.

Antibodies to recombinant heterogeneous nuclear RNP core protein A1 were detected in sera from 27 of 58 patients with rheumatoid arthritis (RA) and from 7 of 31 patients with systemic lupus erythematosus, by immunoblotting and enzyme-linked immunosorbent assay. Protein A1 consists of 2 distinct domains: The N-terminal sequence is identical to a single-stranded DNA binding protein termed UP1, and the C-terminal domain shows a partial homology with keratin. All 7 A1-positive systemic lupus erythematosus sera reacted with UP1, whereas 9 of the 27 A1-positive RA sera did not. In RA, anti-A1 activity was significantly associated with antikeratin antibodies (AKA); these antibodies were present in 23 of 27 A1-positive sera and 10 of 31 A1-negative sera (P less than 0.01). Immunoabsorption with recombinant protein A1 resulted in a significant reduction of AKA titers in 6 of 10 RA sera tested, suggesting that AKA from RA patients may cross-react with the C-terminal portion of the heterogeneous nuclear RNP protein A1.

Adolescent

[131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Forty-two children with advanced neuroblastoma who either failed with first-line therapy or relapsed after achieving a complete remission, were considered for treatment with [131I]metaiodobenzylguanidine (131I-MIBG). We subdivided 42 cases into 5 groups, in accordance with the stage of disease at diagnosis, response to first-line therapy and relapse. A total of 99 courses of 131I-MIBG were administered with doses ranging from 2.8 to 6.0 GBq. One child received six courses, 3 four courses, 18 three courses, 6 two courses and 15 one course of 131I-MIBG. The total delivered dose in single measurable lesions ranged from 286 to 1691 cGy with an uptake factor ranging from 3% to 10%. We obtained a major response in primary tumors, and a long-term response was observed in 5 cases, lasting more than 2 years without further chemotherapy.

3-Iodobenzylguanidine

Results of [131I]metaiodobenzylguanidine treatment in metastatic malignant phaeochromocytoma.

The results obtained with [131I]metaiodobenzylguanidine (131I-MIBG) treatment in 6 patients affected by metastatic phaeochromocytoma are reported. Single doses of 3.7-7.4 GBq were given, in 1-6 courses, up to cumulative doses of 5.4-37.8 GBq. Objective responses were observed in 5 patients (2 tumour shrinkages, even if small; 5 lowering of blood pressure), which were only temporary in 3 patients and stable in 2. Complete disappearance of pain was obtained in 2/2 patients. No adverse side-effects were observed. The problem of treatment strategy in situations of stable disease deserves further study.

3-Iodobenzylguanidine

Results of [131I]metaiodobenzylguanidine treatment in metastatic carcinoid.

The results obtained with [131I]metaiodobenzylguanidine (131I-MIBG) treatment in 6 patients affected by metastatic carcinoid are reported. 131I-MIBG was given in single doses of 3.7-8.0 GBq, reaching a maximum cumulative dose of 29.5 GBq in 4 courses. Objective responses were not observed, but in 4 cases an apparent stabilisation of the disease for more than 1 year was obtained. A subjective response regarding the carcinoid syndrome was observed in 4 cases. No response was seen in 2 cases. No adverse side-effects of any importance were observed, usually being prevented by a mild medication.

3-Iodobenzylguanidine

Anti-SSB/La antibodies in Sjögren's syndrome and related autoimmune diseases. Results of a quantitative immunoassay using a highly purified antigen.

A quantitative immunoassay using a highly purified antigen from HeLa cells has allowed us to detect antibodies to SSB/La in 11/20 patients with primary Sjögren's syndrome (SS), 15/33 with SLE, and 11/35 with progressive systemic sclerosis (PSS). However, positive results were found in only 2/12 patients with idiopathic Raynaud's disease and 2/20 with rheumatoid arthritis, including 4 with secondary SS. Anti-SSB/La were associated with extraglandular manifestations in primary SS, and with a diffuse sclerodermic pattern in PSS. In SS, SLE and PSS, a positive anti-SSB/La test was strongly associated with nodal or spleen enlargement and with an increased level of gamma-globulins. A direct association was also found with positive tests for rheumatoid factors, anti-SSA/Ro and anti-Scl 70. An inverse relationship was however found with anti-nRNP +/- Sm and anticentromere antibodies. Our data suggest that anti-SSB/La antibodies can be regarded as a marker of B-lymphocyte activation in patients with either primary SS, SLE or PSS.

Antibodies, Antinuclear