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The onset of resistance to drug-induced apoptosis of tumour cells is a major problem in cancer therapy. We studied a drug-selected clone of promyelocytic HL-60 cells, called HCW-2, which display a complex resistance to a wide variety of apoptosis-inducing agents and we found that these cells show a dramatic increase in the expression of heat shock proteins (Hsps) 70 and 27, while the parental cell line does not. It is known that stress proteins such as Hsps can confer resistance to a variety of damaging agents other than heat shock, such as TNF- α, monocyte-induced cytoxicity, and also play a role in resistance to chemotherapy. This elevated expression of Hsps is paralleled by an increased activity of mitochondrial metabolism and pentose phosphate pathway, this latter leading to high levels of glucose-6-phosphate dehydrogenase and, consequently, of glutathione. Thus, the apoptotic-deficient phenotype is likely because of the presence of high levels of stress response proteins and GSH, which may confer resistance to apoptotic agents, including chemotherapic drugs. Moreover, the fact that in HCW-2 cells Hsp70 are mainly localised in mitochondria may account for the increased performances of mitochondrial metabolism. These observations could have some implications for the therapy of cancer, and for the design of combined strategies that act on antioxidant defences of the neoplastic cell. [ABSTRACT FROM AUTHOR]

Apoptosis plays a crucial role in immunosenescence, as also evidenced by the increased expression of Fas in lymphocytes from aged people. However, little is known about the genetic regulation of Fas and its ligand, FasL. We have studied their polymorphisms in 50 centenarians and 86 young donors living in Northern Italy. The first Fas polymorphism, at position -670, has in Caucasian a heterozigosity of 51%; the second, at -1377 position, has the wild type allele (G) with a very high frequency (83%) respect to the mutant allele. Genotype and allele distribution for both polymorphisms were similar in controls and centenarians. Similar results were found as far as two FasL polymorphisms (IVS2nt-124 and IVS3nt169) are concerned. On the whole, our data suggest that Fas and FasL polymorphisms, as well as their haplotypes, are unlikely to be associated with successful human longevity. [ABSTRACT FROM AUTHOR]

Since 1988 in the referral area of the Neurosurgical Unit of Cesena, Italy, a protocol for prevention of deterioration in minor head injury was adopted. Adult patients admitted to any hospital with a GCS score of 15 and 14 (transient) without neurological deficit are submitted to skull x-ray: if a fracture is present the patient is sent for CT to the nearest regional Center. In children skull x-ray is not routinely performed and the patients are admitted for observation to the nearest regional hospital. To assess the effects of such a protocol on morbidity and mortality of extradural haematoma (EDH), from June 1989 to September 1991 a consecutive series of 95 patients harbouring a significant acute EDH was collected. Mean age was 31 years; in 70% trauma was caused by a road traffic accident. The patients were divided into 3 categories: If we compare these results with those of a previous study of our group done in 1980-86, there is a statistically significant difference concerning both mortality and morbidity. Our protocol proved therefore to be adequate in preventing most deaths that occurred following clinical deterioration in an apparently low risk patient. [ABSTRACT FROM AUTHOR]

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Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)