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Biomedical subjects

B Bonetti

Publications and source records attributed to B Bonetti.

At least 37 records · Page 2Linked to original sources
PubMed1995

Astrocytes upregulate glial fibrillary acidic protein (GFAP), but not insulin-like growth factor-I (IGF-I) during experimental autoimmune neuritis (EAN).

T cell-mediated autoimmune neuritis produces rapid activation of spinal cord microglia. To determine whether this microglial response upregulates astrocytic expression of IGF-related proteins, we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein (GFAP), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGFR-I) and IGF binding protein-2 (IGFBP-2). Relative levels of GFAP mRNA and peptide were highest in the lumbar spinal cord 4-10 d following T cell transfer and significant GFAP elevations were still present after three weeks. The astrocytes expressing GFAP mRNA and peptide were localized around motoneurons which were related topographically to axons in peripheral nerve inflammatory lesions. In the nucleus gracilis, where terminals of dorsal root ganglion neurons are located, astrocytic levels of GFAP mRNA and peptide rose later and did not reach their highest levels until 21 d after T cell transfer. Even though microglia were activated in both locations 2-4 d after transfer, astrocytic levels of IGF-I, IGFR-I and IGFBP-2 mRNA and peptide did not differ significantly from those observed in controls. The dissociation of GFAP and IGF-I expression in EAN suggests that these astrocytic responses may be independently regulated. We also suggest that the type and severity of remote neuronal injury are probably more important inducers and regulators of these astrocytic responses than microglial cell activation.

Animals↗
PubMed1994

Premature translation termination mutations are efficiently suppressed in a highly conserved region of yeast Ste6p, a member of the ATP-binding cassette (ABC) transporter family.

The requirements for efficient translation termination are incompletely understood. Since the local context surrounding stop codons can influence the efficiency of translation termination, premature termination codons introduced by random mutation may not always terminate at the optimal efficiencies expected of naturally occurring stop codons. To investigate whether this could result in physiologically significant levels of read through, we examined the suppression of premature translation termination mutations within a sequence motif of the yeast Ste6 protein (Ste6p) that is highly conserved among members of the ATP-binding cassette (ABC) transporter family. The human cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in individuals with the disease cystic fibrosis, is also a member of this protein family. The mutations examined in Ste6p were chosen because a premature termination codon at the corresponding residue of CFTR has previously been reported to cause less severe pulmonary involvement than some missense mutations, suggesting that low level suppression of this stop codon could be occurring. Our results indicate that these premature stop codons in Ste6p can be suppressed at frequencies as high as 10%. Characterization of this phenomenon using a beta-galactosidase read through assay system showed that a limited sequence context surrounding this site contained information that was sufficient to cause suppression of translation termination. Amino acid sequence analysis of the full-length translation products produced by read through of an amber codon demonstrated that termination suppression was mediated by near-cognate tRNA mispairing that resulted in the insertion of tyrosine, lysine, or tryptophan.

ATP-Binding Cassette Transporters↗
PubMed1994

Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy.

We studied the frequency and clinical correlates of different IgM specificities in 75 patients with neuropathy associated with IgM monoclonal gammopathy. Patients were tested for IgM reactivity with the myelin-associated glycoprotein, P0, neurofilaments, and tubulin by immunoblot; with GM1, asialo-GM1, GM2, GD1a, GD1b, sulfatide, and chondroitin sulfate C by enzyme-linked immunosorbent assay; and with brain and nerve glycolipids by overlay high-performance thin-layer chromatography. Forty-two patients (56%) had high titers of IgM antibodies to MAG; 4 (5%), to sulfatide (1 also to myelin-associated glycoprotein); 4 (5%), to the 200-kd neurofilament (2 also to myelin-associated protein); and 1 each, to GD1b and chondroitin sulfate C. No reactivity was found in 26 patients (35%). More patients with anti-myelin-associated glycoprotein IgM (62%) than with unknown IgM reactivity (31%) had a predominantly sensory neuropathy (p < 0.025). Nerve conduction findings were consistent with a demyelinating neuropathy in 77% of patients reactive to myelin-associated glycoprotein and 24% with unknown reactivity (p < 0.0001) and the mean conduction velocity of peroneal nerve was lower in the former group (22.9 m/sec) than in the latter group (39.6 m/sec) (p < 0.000001). Patients with anti-sulfatide IgM had a sensorimotor neuropathy with morphological evidence of demyelination while anti-neurofilament IgM was not associated with homogeneous findings. Patients with anti-GD1b or anti-chondroitin sulfate C IgM had a predominantly motor impairment. The frequent occurrence of anti-neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.

Adult↗
PubMed1994

Expression of insulin-like growth factor-I and related peptides during motoneuron regeneration.

The regulation of insulin-like growth factor-I (IGF-I) and related peptides during motoneuron regeneration was examined in the facial nerve following facial nerve transection. One to 39 days after axotomy, the mRNAs and peptides of IGF-I, type-I insulin-like growth factor receptor (IGFR), insulin-like growth factor binding proteins 1-5 (IGFBP-1-5), and glial fibrillary acidic protein (GFAP) were assayed in brain stem sections by in situ hybridization and immunohistochemistry. Relative mRNA levels of IGF-I, IGFR, IGFBP-2, and GFAP in the ipsilateral facial nucleus were highest 4-7 days after transection and declined thereafter. Double immunostaining experiments showed that both IGF-I and IGFBP-2 were localized in GFAP-positive astrocytic processes, many of which were perineuronal. Peak staining intensity was found 4-7 days after transection and immunoreactivity still was present after 21-35 days. IGFR mRNA was found in some regenerating neurons; however, IGFR peptide was not detected in these neurons or in any other cells in the facial nucleus. Our findings suggest that astrocytic production of IGF-I and IGFBP-2 may accompany regeneration of neurons undergoing retrograde changes induced by axotomy.

Animals↗
PubMed1994

Increased serum levels of ICAM-1, ELAM-1 and TNF-alpha in inflammatory disorders of the peripheral nervous system.

Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-alpha were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms.

Adult↗
PubMed1993

Human peripheral nerve macrophages in normal and pathological conditions.

We investigated, by immunocytochemistry and immune electron microscopy, the immunophenotype, morphology and functional properties of human peripheral nervous system (PNS) macrophages (M phi) under normal and pathological conditions. Endoneurial M phi disclosed an elongated, ramified morphology, with the main processes oriented along the major axis of nerve fibers; they shared several lineage-related and functional markers with monocyte/macrophages and central nervous system (CNS) microglia, including CD4, CR3, CR4 and FcRIII. In addition, basal expression of HLA-DR antigens was exclusively confined to M phi in normal PNS. In the course of unrelated pathological conditions, resident M phi underwent activation with transformation to hypertrophic cells or foamy phagocytes and up-regulation of the markers expressed in normal conditions; new expression of a macrophagic antigen was detected on activated M phi. In different neuropathies, HLA-DR expression was also detected on non-myelin forming Schwann cells with ultrastructural features indicative of denervation. The present results demonstrate that the human PNS is provided with an intrinsic population of immunocompetent and potentially phagocytic M phi, which represent the peripheral counterpart of CNS microglia.

Adolescent↗
PubMed1992

AZT-induced mitochondrial myopathy.

Histochemical, electron microscopy and biochemical studies were performed on muscle biopsy specimens from 11 AIDS patients treated with zidovudine. A peculiar association of structural abnormalities and mitochondrial dysfunction was found. Focal cytochrome c oxidase (COX) deficiency was evident in muscle sections from 9 patients, 8 of whom had received long-term treatment while one had been treated for 1 month only. Electron microscopy showed changes in number, size and structure of mitochondria. Biochemical studies proved partial COX and succinate cytochrome c reductase (SCR) deficiency in 4 patients; one patient had only reduced SCR activity. Our data confirm that AZT therapy can cause toxic myopathy with mitochondrial dysfunction.

Adult↗
PubMed1992

Complement neoantigen and vitronectin are components of plaques in amyloid AL neuropathy.

We studied three patients with late onset, chronic sensorimotor and autonomic neuropathy in course of plasma cell dyscrasia with Bence Jones proteinuria. Histopathological findings of nerve biopsies consisted in diffuse loss of myelinated and unmyelinated fibers associated with perivascular deposits of amorphous material with physico-chemical and ultrastructural features of amyloid. By immunohistochemistry, light chains of the same type as Bence Jones protein, components of the classic and lytic pathways of the complement and vitronectin were detected at the level of amyloid nodules. The colocalization of complement neoantigen and vitronectin suggests that this complex derives from the circulation. The elucidation of the chemical composition of amyloid might shed some light in the pathogenesis of these disorders.

Amyloidosis↗
PubMed1992

Inherited neuroaxonal dystrophy in C6 deficient rabbits.

We report the occurrence of a progressive neurological syndrome clinically characterized by subacute motor neuropathy in offspring of C6 deficient rabbits. On the basis of the pedigree analysis, the disease appears to be genetically transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: 1) severe axonal degeneration in the sciatic nerve system involving mainly motor fibers; 2) occasional peripheral axonal enlargement closely associated with axonal degeneration; 3) presence of structured abnormal material in normal-size myelinated fibers of central nervous system (CNS) and peripheral nervous system (PNS); and 4) widespread occurrence of dystrophic axons and axonal spheroids in the gray matter of CNS. By ultrastructural examination, dystrophic axons are filled with tubulovesicular material, stalks of parallel membranes and dense bodies similar to what is described in human neuroaxonal dystrophies (NAD). The disease manifested by C6 deficient rabbits may represent an animal model of primary human NAD.

Animals↗
PubMed1992

[Exclusive radiotherapy in the treatment of carcinoma of the portio cervicis, stage IIB FIGO].

From January 1970 through December 1987, 135 patients with cervical cancer in stage IIB (FIGO criteria) were treated by means of exclusive radiotherapy in the Istituto del Radio of the Brescia University. Thirty cases were treated by exclusive external-beam radiotherapy (RTT), 39 by brachytherapy (CU) plus external-beam radiotherapy, 24 by combined RTT and CU, 41 by RTT + CU + RTT, and 1 case by CU alone. Crude survival at 5 years is 52.4%, and NED survival is 50%. The differences between the values of crude and NED survival by radiotherapy technique were statistically significant (p 0.05), ranging from 69.8% in the RTT + CU group to 35.5% in the RTT alone group. Twenty-four cases (18%) failed to obtain complete remission, and 24 more cases recurred in the pelvis. Sequelae were evaluated by the French-Italian glossary; they were present in 62 cases (46%), but in 12 cases only (9%) they were severe. The incidence of sequelae was highest in the groups of patients treated with the combined techniques (RTT and CU) which allowed best disease control.

Adenocarcinoma↗
PubMed1990

Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy.

We investigated the role of complement in the pathogenesis of the demyelinating polyneuropathy that occurs in some patients with IgM monoclonal gammopathy. Seven patients with chronic sensorimotor polyneuropathy and IgM monoclonal gammopathy were examined. In six patients, the monoclonal protein recognized an epitope shared by myelin-associated glycoprotein and two peripheral-nerve glycolipids, whereas in one patient, IgM bound to an unidentified myelin antigen. Direct and indirect immunofluorescence and immunoperoxidase assays showed colocalization along the myelin sheaths of peripheral-nerve fibers of monoclonal protein with complement components C1q, C3d, and C5. In addition, terminal-complement complex that was not associated with S protein was detected in myelin sheaths. It appeared that alterations in myelin geometry caused by the separation of myelin lamellae corresponded to sites at which terminal-complement complex was deposited. We conclude that demyelination in polyneuropathy associated with IgM monoclonal gammopathy may be mediated by complement.

Aged↗
PubMed1990

AIDS--associated predominantly sensory neuropathy. The role of herpes viruses.

Three patients with predominantly sensory neuropathy in course of HIV-1 infection are reported. In all cases ultrastructural examination showed herpes virus-like particles in the axoplasmic matrix of myelinated fibers and in endoneurial macrophages. In 2 cases clinical patterns of posterior column involvement were observed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Exclusive radiotherapy of stage Ib cervix carcinoma].

From January 1st 1970 to December 31 1987, 178 consecutive cervical cancer Ib patients were treated at the Istituto del Radio, University of Brescia, by means of radiotherapy alone. In spite of the negative selection of the patients (advanced age, poor general conditions, associated pathologies) the results were good: 5-year cumulative survival was 86.5%, with a total failure rate of 13.5% (24 failures: 18 in the pelvis, 3 metastases and 3 both). The incidence of major complications (G2-G3-G4 of the Italian-French glossary) was 20% (36 patients): 19 G2, 15 G3 and 2 G4. The results in terms of survival and complications were related to the prognostic factors of the tumor (histology, grading, tumor size), of the patient (age, Karnofsky scale, associated pathologies, number of erythrocytes and hemoglobin rate) and treatment modalities (total dose, fractionation, combination of intracavitary brachytherapy and external beam).

Adult↗
PubMed1988

[Radiotherapy in T1 epidermoid carcinomas of the vocal cords].

In the last years radiotherapy has become the methodology of choice in the treatment of initial T1a and T1b glottis neoplasias, the reason being-it is as successful in controlling the disease as demolition surgery, but it saves the phonation function. Our experience in the "O. Alberti" Institute of "Spedali Civili" di Brescia from January 1, 1970 to December 31, 1984 is here reported. Out of the total figure of 195 patients treated with radiotherapy, 154 were T1a, and 41 T1b. Global survival rate after 5 years is 76,25%. Loco-regional relapses were on the whole 28: 24 on T, and 4 on N. Saving therapy allowed the retrieval of 15 patients (62,5%) with relapse on T. The total dose administered (greater than 60 Gy or 60 less than Gy), TDF values (greater than 95 or less than 95 on minimum), and field dimensions (greater than 5 x 5 cm2 or less than 5 x 5 cm2) were considered, in order to evaluate the chance of relapse. The only statistical data concerning the significant difference between the two groups of patients irradiated with fields less than 5 x 5 cm2 and more than 5 x 5 cm2, both with a total dose of more than 60 Gy. In the group of patients irradiated with smaller fields, the percentage of relapses is lower. This is probably due to the fact that the patients had more superficial lesions. The treatment had no severe side-effects, and never affected the quality of the voice. In order to obtain a high recovery-rate, in the meantime reducing side-effects and keeping a good phonation function, small fields and dose ranging between 64 and 68 Gray with 32-34 fractions, 5 per week, are thought to be the best. It is necessary, however, to watch out for penumbra and inaccuracy by immobilizing the patient with containing systems.

Carcinoma, Squamous Cell↗
PubMed1988

[Significance of preventive radiotherapy of the neck in clinically N0 tumors of the larynx].

The role of precautionary radiotherapy of the neck in laryngeal cancers (except T1-T2 glottic and some T1 supraglottic cancers) N0 at the clinical staging was investigated. Two-hundred and fifty-three patients were examined: 143 were irradiated only on T, and 110 also on the neck. Radiotherapy of the neck in the latter group was performed either by means of two large opposed fields of photon beams including T and N, or by means of fields of photon beams on T and electron beams (8 x 12 cm2 average) on the neck, to quite exclude any risks for the spinal cord. The dose was 45-50 Gy (2 Gy/fraction/day; 5 fraction/week) in 4-5 weeks. A comparison of the results obtained in the two groups, in terms of survival-rate and relapse-free time, indicates that radiotherapy reduces the change of relapses on N (6.1% vs. 14.62% at 3 years; p = 0.04) and improves the patient's survival chances (82.5% vs. 68.4% at 3 years; and 80.8% vs 63.4% at 5 years). Our data were then compared with literature data on the importance of N field size in radiation treatment. As a rule, some authors enlarge the field to be treated to a total nodal neck irradiation, but their results are not significantly different from those we obtained with 8 x 12 cm2 field size.

Cobalt Radioisotopes↗
PubMed1986

Parenteral nutrition of injured patients.

Injured patients treated with fructose 1,6-diphosphate (1 millimole of phosphate per kilogram per day) together with parenteral nutrition had a better nitrogen balance than patients treated with isocaloric nutrition and an inorganic source of phosphate. Excretion of 3-methylhystidine was similar while tyrosine and alanine output from the extremities was lower in the group of patients given fructose 1,6-diphosphate. The data indicates that the protein sparing action of fructose 1,6-diphosphate is exerted through an increased protein synthesis.

Abdominal Injuries↗
PubMedDate not supplied

[Rhinopharyngeal carcinoma. Clinical prognostic factors].

The authors report the results of the retrospective analysis of 306 patients with nasopharyngeal carcinoma. All patients had received high-dose radiation therapy. First, overall results were analyzed, and then the prognostic value of the patients' data (age and sex) and of tumor features (histology, local spread, lymph node involvement). Crude actuarial survival rate is 42.9% (+/- 2.9) at 5 years; loco-regional control at the end of treatment was obtained in 16.8% of cases; 53.6% of them (126 patients) had relapses, especially on T and M. Cumulative relapse rate was 51.1% (+/- 3.3) at 5 years. Mean relapse-free interval was 10 months. All the clinical factors we examined had prognostic value; especially local tumor spread, with a worse prognosis for tumors with extra-nasopharyngeal spread (5-year survival: 38.3% +/- 6.9 for T3 and 33.9% +/- 4.8 for T4), and especially for tumors with neurological deficits (5-year survival: 19.9% +/- 6.3). Regional lymph node metastases were an important factor too, with a special emphasis on size (5-year survival: 26.4% +/- 6.5 in the cases with adenopathies with phi greater than 6 cm), and fixed adenopathies (5-year survival: 23.9% +/- 4.6). These prognostic factors are considered only in part in the current TNM 1987 staging system, which calls for its partial revision.

Adolescent↗