c-Fos proto-oncoprotein is a short-lived transcription factor with oncogenic potential. We have shown that it is massively degraded by the proteasome in vivo under various experimental conditions. Other proteolytic systems including lysosomes and calpains, might, however, also marginally operate on it. Although there is evidence that c-Fos can be ubiquitinylated in vitro, the unambiguous demonstration that ubiquitinylation is necessary for its addressing to the proteasome in vivo is still lacking. c-Jun, one of the main dimerization partners of c-Fos within the AP-1 transcription complex, is also an unstable protein. Its degradation is clearly proteasome- and ubiquitin-dependent in vivo. Interestingly, several lines of evidence indicate that the addressing of c-Fos and c-Jun to the proteasome is, at least in part, governed by different mechanisms. c-Fos has been transduced by two murine osteosarcomatogenic retroviruses under mutated forms which are more stable and more oncogenic. The stabilization is not simply accounted for by simple deletion of c-Fos main destabilizer but, rather, by a complex balance between opposing destabilizing and stabilizing mutations. Though mutations in viral Fos proteins confer full resistance to proteasomal degradation, stabilization is limited because mutations also entail sensitivity to an unidentified proteolytic system. This observation is consistent with the idea that Fos-expressing viruses have evolved to ensure control protein levels to avoid high protein accumulation-linked apoptosis. In conclusion, the unveiling of the complex mechanism network responsible for the degradation of AP-1 family members is still at its beginning and a number of issues regarding the regulation of this process and the addressing to the proteasome are still unresolved.

Animals↗

PubMedDate not supplied

Benign breast surgical biopsies: are they always justified?

AIM OF THE STUDY: To evaluate the indications for open surgical biopsy of breast lesions resulting in a benign histologic report. METHODS: A consecutive series of 754 benign breast biopsies was collected from six Italian centers previously participating in a multicenter study on the benign/malignant biopsy ratio. Histologic diagnosis, diagnostic tests performed, final clinical diagnosis and the indication for surgical biopsy were compared. RESULTS: Fibrocystic alterations represented the most frequent histologic type (43.2%), followed by fibroadenomas (34.5%). Atypical hyperplasia, phyllode tumors and cancer-like lesions (radial scar, sclerosing adenosis) accounted for a minority of cases. The diagnostic approach was different among centers, with mammography, ultrasonography or cytology being underused in some of them. Suspicion of cancer was an indication for surgical biopsy in 66.7% of cases. In the remaining cases the final report was negative or benign, but biopsy was advised for growing lesions (11.3%) or for cosmetic (3%) or psychological reasons (8.2%). In 4% of cases surgical biopsy was presumably advised for the concurrent influence of high-risk conditions such as previous breast cancer (0.7%), family history of breast cancer (2%) or contralateral synchronous breast cancer (1.3%). In 6.8% of the cases biopsy was advised elsewhere for unknown reasons. The indications for biopsy differed among centers, with one center having a low rate of suspicious cases (37%) and a high rate of reported "cosmetic" or "psychological" reasons (47%). CONCLUSIONS: Leaving aside differences in diagnostic approach and aggressiveness, two thirds of all lesions were biopsied in order to exclude cancer. The routine use of a more complete diagnostic protocol and/or alternative methods to obtain a histologic diagnosis (e.g. core biopsy) might substantially reduce the need for open surgical biopsy.

Adolescent↗

PubMedDate not supplied

[Otorhinolaryngologic aspects of the Kimmerle abnormality].

Explore the source record for details and available documents.

Adult↗

PubMedDate not supplied

The biological activities of gro beta and IL-8 on human neutrophils are overlapping but not identical.

Gro beta and IL-8 are two members of the small induced secreted (SIS) cytokine family (C-X-C subgroup) with proinflammatory activities on neutrophils. In order to assess whether or not the interaction with their receptors results in similar biological actions, we compared the two cytokines in five different bioassays. Gro beta showed similar biological activities as IL-8 in tests of chemotaxis, induction of the respiratory burst, and induction of interleukin 6 (IL-6) production. However, for two other biological activities: augmentation of the expression of CD11b on the cell surface and rapid elevation of the intracellular calcium concentration, maximal effects required 100 times more gro beta than IL-8. Taken together, these results suggest that the stimulation of the IL-8 or gro beta receptor evokes three similar responses, but that only the activation of the IL-8 receptor and not that of gro beta results in elevated CD11b expression and calcium mobilization in human neutrophils.

Antimicrobial Cationic Peptides↗

PubMedDate not supplied

[Future of immunologic therapy of bronchogenic carcinoma].

The AA. report their experience as to the treatment applied to patients suffering from unremovable bronchial cancers. They can therefore stress the results obtained by chemotherapeutic treatment associated to thymopentin as well as interferon-thymopentin treatment. Elderly patients were subjected to interferon-thymopentin therapy, which helped in improving their life standard and survival.

Adult↗

PubMedDate not supplied

[Comparative evaluation of echography, computerized tomography and magnetic resonance imaging in the diagnosis of hepatocellular carcinoma in cirrhotic patients].

The contribution of US, CT, and MR imaging was investigated in 25 cirrhotic patients with hepatocellular carcinoma. The following parameters were considered: lesion detection, site and size of the lesion, daughter nodules, location and/or infiltration of intrahepatic vessels, patency of portal vein and collateral vessels, signs of chronic liver disease, steatosis, ascitis, and lymphadenopathy. Our results confirm the value of US, which also allowed lesion biopsy in all cases. CT was as accurate as US in detecting the lesion and even superior in demonstrating daughter nodules. MR imaging, with conventional SE and IR sequences, was inferior since it missed 3 lesions due to motion artifacts; moreover, a smaller number of daughter nodules was seen than with CT. The authors conclude that, at present, MR imaging cannot replace US and CT; the latter, if combined with arteriography, using either hydrosoluble or liposoluble contrast agents, gives the best results in the detection of small hepatocellular carcinomas, and especially of daughter nodules which are important factors for planning appropriate therapy.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

[Beta 2 microglobulin in the diagnosis of reflux nephropathy in childhood].

The authors determined beta 2 microglobulin plasmatic and urinary levels in 35 children aged 1 month-14 years; 25 of them were suffering from reflux nephropathy. The results of this study indicate that B2 microglobulin concentrations in plasma and urine can be useful parameters to the clinical diagnosis and evaluation of severity of reflux nephropathy. In presence of reduced glomerular filtration rate B2 microglobulin plasmatic levels resulted significantly out of the normal range (mean = 3318; s.d. = 1184) and proportional to the residual functionality degree (p 0.005); blood B2 microglobulin values demonstrated a higher specificity (76.2%) than creatine clearance. Moreover Bt (B2 microglobulin urinary level), Bs (B2 microglobulin excretion per minute corrected to surface area) and Bf (B- microglobulin excretory fraction) were shown to vary (p 0.025) in relation to the presence and the degree of tubulo-interstitial damage. In particular, Bf values progressively impairing with the severity of the nephropathy, were shown to have a statistically good distribution and the best sensibility (95.2%) and specificity (77.8%) in detecting tubular damage.

Adolescent↗

PubMedDate not supplied