Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996-2005.

BACKGROUND: In 1997, a Monograph from the International Agency for Research on Cancer (IARC) classified occupational exposure to crystalline silica as carcinogenic to humans. Large amounts of epidemiological data have been published subsequently. METHODS: We conducted a systematic review of epidemiological investigations on silica exposure and lung cancer risk published after the IARC Monograph, including 28 cohort, 15 case-control and two proportionate mortality ratio (PMR) studies. These were identified in the available literature. RESULTS: The pooled RR of lung cancer, calculated using random effects models, from all cohort studies considering occupational exposure to silica was 1.34. The RRs were 1.69 in cohort studies of silicotics only, 1.25 in studies where silicosis status was undefined and 1.19 among non silicotic subjects. The pooled RR was 1.41 for all case-control studies. The RRs were 3.27 in case-control studies of silicotics only, 1.41 in studies where silicosis status was undefined and 0.97 among non silicotic subjects. The RR was 1.24 for PMR studies. CONCLUSIONS: In this re-analysis, the association with lung cancer was consistent for silicotics, but the data were limited for non silicotic subjects and not easily explained for undefined silicosis status workers. This leaves open the issue of dose-risk relation and pathogenic mechanisms and supports the conclusion that the carcinogenic role of silica per se in absence of silicosis is still unclear.     

An alternative approach in the surgical treatment of infectious endocarditis. The fresh antibiotic-sterilized aortic valve homograft

Following the pioneering work of Ross and Barratt-Boyes, there is currently a strong evidence based on long-term follow-up data that valve homografts are the best valve substitutes in the aortic position. Currently there exists a renewed interest in the use of fresh and cryopreserved homografts as we know that homografts show a prolonged durability together with the lack of thromboembolic complications. Here we present the case histories of 3 patients undergoing aortic valve replacement by fresh homografts sterilized in antibiotic solution. The underlying pathology was infective endocarditis in all 3 patients, a disease that is considered the ideal indication for homograft implantation. Technical details at the time of implantation, their advantages with regard to other replacements devices and the whole process of procurement, manipulation and preservation are commented on.     

Aortic valve replacement by a pulmonary homograft

Minor experience still exists in our country with regard to the use of valve homografts in cardiac surgery. Only a few implantations have been performed in cases of right ventricular outflow tract reconstruction in addition to our own experience in cases of infective endocarditis of the aortic valve. We present a case of aortic valve replacement by using an antibiotic-sterilized fresh pulmonary valve autograft. The case is described and the possible advantages of the use of pulmonary allografts in the aortic position are discussed.     

Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

Synchronous associations of tumors in the pelvic organs of the female genital tract]

The Authors report their findings concerning the synchronous associations of tumours involving pelvic organs in the female genital tract observed at the Gynecological Clinic, Aquila. From January 1980 to December 1991, 9 cases (4.28%) of synchronous tumours were found in a total of 210 cases of womb, ovary and vagina tumours. The paper examines the clinical problems and questions of anatomopathological characterisation raised by these associations.     

Substance abuse and psychopathology

This report evaluates, using DSM III, the psychopathological profile of 226 heroin users taken in at the clinical centre of "Cascina Verde" Therapeutic Community (Milan, Italy) and admitted to a psychotherapeutic, retraining, integrated, both out-and-in-patient treatment. The outcome shows that 30% of subjects are to be diagnosed according to Axis I while 61% are to be considered among Axis II personality disorders. A portion of 16% is to be referred to the "schizophrenic spectrum", 25% has histrionic, narcissistic, antisocial and borderline personality disorders and the remaining are to be referred to an extremely heterogeneous category. The report shows also data concerning Axes IV and V, always according DSM III.     

Mapping antigenic sites of an immunodominant surface lipoprotein of Mycoplasma agalactiae, AvgC, with the use of synthetic peptides

As a first step toward the design of an epitope vaccine to prevent contagious agalactia, the strongly immunogenic 55-kDa protein of Mycoplasma agalactiae was studied and found to correspond to the AvgC protein encoded by the avgC gene. The avg genes of M. agalactiae, which encode four variable surface lipoproteins, display a significant homology to the vsp (variable membrane surface lipoproteins) genes of the bovine pathogen Mycoplasma bovis at their promoter region as well as their N-terminus-encoding regions. Some members of the Vsp family are known to be involved in cytoadhesion to host cells. In order to localize immunogenic peptides in the AvgC antigen, the protein sequence was submitted to epitope prediction analysis, and five sets of overlapping peptides, corresponding to five selected regions, were synthesized by Spot synthesis. Reactive peptides were selected by immunobinding assay with sera from infected sheep. The three most immunogenic epitopes were shown to be surface exposed by immunoprecipitation assays, and one of these was specifically recognized by all tested sera. Our study indicates that selected epitopes of the AvgC lipoprotein may be used to develop a peptide-based vaccine which is effective against M. agalactiae infection.     

Chemokines and pro-inflammatory cytokines in Down's syndrome: an early marker for Alzheimer-type dementia?

BACKGROUND: People with Down's syndrome (DS) show early Alzheimer-like dementia. It has been suggested that the pro-inflammatory cytokine class plays a role in Alzheimer's disease (AD). The study aims at verifying whether pro-inflammatory cytokines in DS are correlated with age, affective symptoms and intellectual decline to a different degree than in subjects with non-DS learning disabilities. METHODS: Cases: 19 subjects with DS; controls: sex- and age-matched individuals with learning disabilities caused by perinatal ischaemic damage. The level of mental retardation was assessed according to DSM-IV; psychopathological symptoms were measured by the Assessment and Information Rating Profile. Serum levels of cytokines were determined with ELISA. RESULTS: DS patients showed higher levels of cytokines and chemokines, with the exception of RANTES; but the only significant difference detected was for MIP-1alpha. A correlation between the degree of mental retardation and IL-6, and between MIP-lalpha and age was found in patients with DS, but not in controls. CONCLUSIONS: The data obtained suggest a possible involvement of chemokines in the inflammatory and degenerative processes similar to AD in DS. Further longitudinal research is required to confirm these findings.     

A human leucocyte antigen-DR1 transgene confers susceptibility to experimental allergic encephalomyelitis elicited by an epitope of myelin basic protein

Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA-restricted presentation of T-cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA-DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13-33, 87-106 and 139-154 bound by HLA-DR1. We report here that HLA-DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13-33 epitope induced a strong T helper 1 (Th1) response accompanied by high T-cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139-154) or no disease (87-106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.