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There is growing evidence that metal ions can accelerate the aggregation process of several proteins. This process, associated with several neuro-degenerative diseases, has been reported also for non-pathological proteins. In the present work, the effects of copper and zinc ions on the denaturation and aggregation processes of beta-lactoglobulin A (BLG-A) are investigated by differential scanning calorimetry (DSC), fluorescence, electron paramagnetic resonance (EPR) and optical density. The DSC profiles reveal that the thermal behaviour of BLG-A is a complex process, strongly dependent on the protein concentration. For concentrations 0.13 mM an exothermic peak also appears, above 90 degrees C, related to the aggregation of the denaturated BLG-A molecules. The thioflavin T fluorescence indicates that the thermally induced aggregates show fibrillar features. The presence of either equimolar Cu(2+) or Zn(2+) ions in the protein solution has different effects. In particular, copper binds to the protein in the native state, as evidenced by EPR experiments, and destabilizes BLG-A by decreasing the denaturation temperature by about 10 degrees C, whereas zinc ions probably perturb the partially denaturated state of the protein. The kinetics of BLG-A aggregation shows that both metal ions abolish the lag phase before the aggregation starts. Moreover, the rate of the process is 4.6-fold higher in the presence of copper, whereas the effect of zinc is negligible. The increase of the aggregation rate, induced by copper, may be due to a site-specific binding of the metal ion on the protein.

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The aim of this study was to evaluate the effectiveness of a recently developed radiolabelled somatostatin analog (111In-pentetreotide) for the detection and localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and to compare the results obtained with the results of 99mTc(V)-DMSA, and radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9 patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9 patients with known lesions of carcinoid tumor. It gave a negative result in 2 MTC patients with high levels of calcitonin but with no evidence of disease at conventional diagnostic modalities. The scintigraphic results were comparable with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the modifications of calcitonin levels brought about by the acute administration of octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients studied.

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Thirty-one children examined for gastroesophageal (GE) reflux were studied with both barium meal X-ray and gastroesophageal scintigraphy. The study was performed with a double-blind method. The children with negative findings at both tests were submitted to intraluminal esophageal pH probe test. Barium X-ray detected GE reflux in 17/27 patients, whereas radionuclide scintigraphy was positive in 24/27 (positivity: 63% versus 89%; p less than 0.05). Their combined use provided positive findings in 26/27 cases. Scintigraphy appeared to be a safe and reliable screening test to detect GE reflux. Moreover, scintigraphy was superior to barium X-ray study for it had higher diagnostic accuracy, it could be easily performed on young patients, and delivered smaller radiation doses.

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Gallbladder and cystic duct agenesis is a rare malformation with frequent familial occurrence. We report a case in a girl, diagnosed by nonoperative means, and a second case in her brother, discovered with a screening in the same family, operated with ultrasonography.

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In the last years, total bone scan has gained an important place in the staging of the neoplasms of the lung. Out of 271 patients with lung cancer who underwent a bone scan in the period october 1979-october 1980. 10 showed an increased fixation of the isotope with a linear pattern along the diaphysis of the limbs. These findings, clinically silent, suggested the diagnosis of hypertrophic osteoarthropathy, which has been subsequently confirmed radiologically. The different pathogenetic theories and the evolution of the scintigraphic picture after therapy of the primary disease are briefly discussed.

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Out of 874 patients undergoing radiotherapy for carcinoma of the uterine cervix, 31 cases (3.5%) of second primary malignant tumour in another site were encountered. Half the cases preceded and half followed uterine cancer. The data are analysed and discussed.

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