Experimental radioinduction of chromosomal variants in man.
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Biomedical subjects
Publications and source records attributed to A Antonelli.
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FRTL-5 rat thyroid cells were either surface-labeled with 125I or biosynthetically labeled with [3H]N-acetylglucosamine, solubilized by lithium diiodosalicylate and immunoprecipitated after sequential exposure to bovine thyrotropin and anti-bovine thyrotropin. Autoradiography of polyacrylamide gels run under denaturing conditions and in the presence of a reducing agent revealed two prominent bands with approximate molecular weights of 66-70 kDa and 47 kDa. Immunoprecipitation of the same radiolabeled and solubilized membrane preparations with a Graves' disease IgG having thyroid stimulating but no thyrotropin-binding inhibiting activity revealed only one major band, migrating near the 47 kDa component reactive with thyrotropin. No bands were immunoprecipitated in control incubations using normal human IgG or substituting radiolabeled, solubilized membranes from a rat thyroid cell line with no thyrotropin receptor activity. Thin layer chromatography of Folch extracts of the [3H]-N-acetylglucosamine-labeled immunoprecipitates obtained by either procedure indicated that a specific thyroid ganglioside was coprecipitated with the immunoprecipitated proteins in both cases.
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Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long-term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding-inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone-iodine-induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.
L-Asparaginase (ASNase), a drug widely used in the treatment of acute lymphoblastic leukemia, has been reported to decrease serum T4-binding globulin (TBG) levels, while results of serum albumin determinations were conflicting. This effect in vivo has been attributed to depressed liver protein synthesis, but this hypothesis has not been proved. To investigate this problem, human hepatoma (Hep G2) cells were continuously labeled for 4 h with 100 microCi/ml [35S]methionine in the absence or presence of graded amounts of ASNase (from 0.1 nM to 0.1 mM). Media and cell lysates were collected, immunoprecipitated with antialbumin or anti-TBG serum and protein A, and submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were sliced, and the radioactivity was counted in a beta-counter. A dose-dependent inhibition of TBG and albumin biosynthesis (as well as of total protein synthesis) was demonstrable, but TBG appeared to be more sensitive to the action of the drug. In fact, TBG biosynthesis was reduced by 8% with 0.1 nM ASNase, while an effect on albumin was observed only at 1 nM ASNase; 50% inhibition was obtained with 30 nM ASNase in the case of TBG and with 800 nM in the case of albumin. At the highest concentration (0.1 mM), TBG biosynthesis was reduced by 94%, and albumin biosynthesis by 75%. ASNase also proved to have a time-dependent effect, as assessed by the measurement of radioimmunoassayable TBG in the media from Hep G2 cells grown in the presence of 10 nM ASNase for 1-4 days. The TBG concentration was progressively reduced, by 40% after 1 day to 85% after 4 days. In pulse-chase experiments, a reduction of total (intracellular plus secreted) immunoprecipitable TBG and, to a lesser extent, albumin was observed, suggesting that the drug also affected the catabolism of newly synthesized proteins. These results provide the first in vitro evidence that ASNase actually inhibits TBG biosynthesis. This effect is not specific for TBG, but this protein appears to be more susceptible than albumin to ASNase action. This can explain why in patients treated with ASNase for leukemia, a decrease in serum TBG concentrations has not always been associated with a reduction in serum albumin levels.
This paper presents the results of two experiments on evoked otoacoustic emissions (EOAEs). The first experiment was conceived to study in the same subjects the temporal stability of the response waveforms, over a period of about four years. A second experiment studied the influence of the relative position between the head and the body on the responses. The generation of EOAEs is then discussed on the base of a first approximation model of the cochlea.
In the present study we examined cells from several patients clinically diagnosed as having ataxia-telangiectasia (AT), for the capacity of their cells to inhibit DNA synthesis following exposure to gamma irradiation, and for the rate of spontaneous or bleomycin-induced chromosomal aberrations. Cells from two patients showed normal inhibition of DNA synthesis and levels of induced chromosomal aberrations intermediate between normal and AT cells. These two patients had only minimal immunologic impairment. These findings appear to define one distinct subset of AT.
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Endoscopy was used over a five-year period to determine the cause of acute or chronic gastrointestinal (GI) tract bleeding in 46 patients receiving long-term hemodialysis. Nine (19%) of the patients were found to be bleeding from telangiectasias. We observed the occurrence of such lesions in the stomach, the small bowel, and the colon. Endoscopic cauterization of the lesions in three patients and jejunal resection in another stopped previously recurrent GI tract bleeding.
Cytogenetic investigations performed on lymphocytes from a 29-year-old woman with no severe anomalies, allowed us to recognize a mild form of Roberts syndrome. The proposita's metaphases showed a consistent centromere splitting, especially affecting chromosomes 16, 19, 21, and 22. This centromere separation sequence seems to be unique to Roberts syndrome cells. The experiments also showed that no diffusible factor, involved in the mechanism of sister chromatid pairing-disjunction, exists.
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Short latency (10 ms post-stimulus-time) auditory evoked potentials are a useful tool for assessing the hearing integrity at different frequency bands, especially if frequency-specific stimuli, like tone bursts, are used. However, a proper interpretation of the evoked potentials should rely upon the understanding of the single auditory nerve units activity patterns and their relations with the gross potentials, under the same stimulating conditions. In this paper, the basic properties of the burst evoked PST histograms of single units are explained with the aid of a model for the cochlear events. The relationships between single units activity and the gross potentials are then analysed on this ground, in particular for what concerns the Action Potential input-output latency curve, the off-response rising at the burst offset and the growth of N2.
The Rate-linked modifications observed in the Auditory Brainstem Responses (A.B.R.) in normal subjects are now well known. On the other hand they are a subject of controversy among groups studying multiple sclerosis (M.S.). 49 patients were observed in parallel studies in Milan and Creteil. The A.B.R. obtained for slow stimulus rates (11-21 Hz) were compared to fast ones (51 Hz). The A.B.R. were not significantly modified in 32% of the cases (deterioration: 21%, improvement: 11%). The variations don't seem to depend on the kind of curves involved. This phenomena can be explained by a frequency linked block of conduction of the pathological fibres, either partial or total. These data seem to be specific to demyelinating diseases. A research project is being conducted to study their specificity.
20 normal subjects and 39 patients with multiple sclerosis were the control and the test groups. Auditory brainstem potentials to 60 dB nHL, 11/s clicks, were recorded under ipsilateral broad-band noise masking at S/N ratio of + 60 dB (unmasked condition), + 20 dB, + 10 dB and 0 dB. In the control group the ABP were absent only in 1 subject at S/N = 0 dB. In the group of 16/39 patients with definite multiple sclerosis, 11 had no ABP at S/N = 0 dB, 6 at S/N = + 10 dB and 5 at S/N = + 20 dB. The ABP waveform per se, in the same subjects, was abnormal in 7 and doubtful in 5. These results are discussed in terms of sensitivity, specificity and efficiency of the test to be applied. The best predictive value is achieved by combining a strict morphological criterion with the results of the ipsilateral masking. Moreover, the ipsilateral masking test positive findings are equally distributed in the group of patients with and without signs of neurological involvement of the brainstem.