Hydrogeochemical and isotopic characterization of the Gioia Tauro coastal Plain (Calabria - southern Italy): A multidisciplinary approach for a focused management of vulnerable strategic systems.

This work pursues the hydro-geochemical and isotopic characterization of the complex groundwater system of the Gioia Tauro Plain, one of the most important industrialized and agricultural coastal areas of southern Italy. The anthropic pressure exposes the water resources at risk of depletion and quality degradation making the plain groundwater a system of high scientific and social interest. The plain is characterized by a shallow aquifer, mostly recharged by local rains and a deep aquifer apparently less influenced by local precipitation. Both aquifers are mainly Ca-HCO3 waters except for localized sectors where Na-HCO3, Na-Cl and Ca-SO4 waters are present. In deep aquifer, both prolonged interaction with sedimentary rocks, mainly deriving from the erosion of crystalline rocks, and direct cation exchange represent the primary factors controlling the formation of Na-HCO3 waters. Mixing processes between these waters and either connate brine and/or deep thermal waters contribute to the formation of isolated high salinity Na-Cl-rich waters. In shallow aquifer, inputs of N-rich sewage and agriculture-related contaminants, and SOx emissions in proximity of the harbor are responsible of the increasing nitrate and sulphate concentrations, respectively. The Cl/Br and NO3/Cl ratios highlight contamination mainly linked to agricultural activities and contribution of wastewater. Along the northern boundary, the warmest groundwater (Na-Cl[SO4]) were found close to a bend of the main strike-slip fault system, locally favouring the rising of B- and Li-rich deep waters, testifying the influence of geological-structural features on deep water circulation. Despite the high-water demand, a direct marine intrusion is localized in a very restricted area, where we observed an incipient groundwater-seawater mixing (seawater contribution ≤7 %). The qualitative and quantitative conditions of the shallow aquifer still have acceptable levels because of the relatively high recharge inflow. A reliable hydrogeochemical conceptual model, able to explain the compositional variability of the studied waters, is proposed.

Uterine myomas during pregnancy: a longitudinal sonographic study.

OBJECTIVE: To evaluate volumetric changes of uterine myomas (fibroids) during pregnancy. METHODS: This was an observational, longitudinal and prospective study of 38 consecutive Caucasian women with singleton pregnancies and a total of 42 uterine myomas, enrolled from a cohort of 1492 women who took part in our first-trimester Down syndrome screening program. Myoma volume was evaluated by ultrasound at 11-14, 20-22 and 32-34 weeks of gestation. RESULTS: Mean myoma volume increased significantly throughout pregnancy. Taking a volumetric change of > 10% between gestational periods to be an increase in size, 71.4% of uterine myomas increased in size between the first and second gestational periods, while this percentage was slightly lower (66.6%) between the second and third periods. Logistic regression analysis revealed that greater maternal age was correlated with a reduction/no change in overall myoma size and multiparity was correlated with a decrease/no change between the first and second trimesters, while a higher prepregnancy maternal body mass index (BMI) was correlated with a volumetric increase between the first and second trimesters and a decrease/no change between the second and third trimesters. CONCLUSIONS: Fibroids enlarge during pregnancy regardless of their initial size or local factors, and maternal age, prepregnancy BMI and parity are apparently correlated with these changes.

Heterotopic pregnancy: case report.

Heterotopic pregnancy is the simultaneus development of an intrauterine pregnancy and ectopic pregnancy. It is a potentially fatal condition and rarely occurrs in natural conception cycles. A high incidence of heterotopic pregnancy is reported in pregnancies following an assisted reproduction technique (ART) with embryo transfer in utero. We report the case of heterotopic pregnancy via ART in a 42-year-old primigravida. She presented with pelvic pain and intraabdominal fluid collection. She was treated with laparoscopic surgery. At present the intrauterine pregnancy is in normal evolution.

Laparoscopic management of adnexal masses in postmenopause.

The study included 64 postmenopausal women with adnexal masses. The selection criteria included menopausal status, an ultrasound scan indicating a benign mass and serum levels of CA-125 below the cutoff (35 U/ml). The results of the study confirm that the removal of a cystic mass in postmenopausal patients with laparoscopic surgery is a more valid and acceptable alternative to traditional surgery.

Ovarian endometriotic cyst in a patient with Ellis-van Creveld's syndrome: case report.

Ellis-van Creveld (EvC) syndrome, or chondroectodermal dysplasia, is a rare genetic disorder associated with chondrodysplasia, ectodermal dysplasia, polydactyly, and congenital cardiac malformations. The disorder is due to an autosomal-recessive mutation mapped to chromosome 4p16. It may occur with different phenotypes. The case of an ovarian endometriotic cyst in a patient suffering from EvC syndrome is reported.

Frizzled-1 is down-regulated in follicular thyroid tumours and modulates growth and invasiveness.

The mechanisms of follicular thyroid carcinoma (FTC) transformation and progression are not well understood. Previously, we detected LOH at 7q21 in all FTCs examined, indicating that loss of genetic material in that region is a common trait in these lesions. To analyse the effects of LOH on gene expression, we performed an analysis of the mRNA expression levels of six different genes, located at 7q21.1-7q21.3. A total of 23 lesions, including eight follicular hyperplasias (FHs), eight follicular adenomas (FAs), two FTCs and five papillary thyroid carcinomas (PTCs) were analysed. The Frizzled-1 (FZD-1) gene, located at 7q21.13, showed the lowest levels of mRNA expression. Down-regulation of FZD-1 expression was also confirmed in an independent series of 69 follicular neoplastic lesions compared to 25 PTCs, analysed by quantitative RT-PCR. In vitro studies showed that FZD-1 expression was also markedly reduced at both protein and mRNA levels in three FTC-derived cell lines (FRO, WRO and FTC-133), while it was normal in the three PTC-derived cell lines (Ca300, Ca301 and K1) examined. We demonstrated that over-expression of FZD-1 in 3 FTC-derived cells decreased invasiveness and proliferation rate, indicating a possible pathogenetic role. In addition, FZD-1 RNA interference in the PTC-derived cell line K1 increased invasiveness. Our data indicated that FZD-1 is involved in growth of follicular tumours and may be considered as a novel marker of this type of tumour.

Identification of a novel polymorphism in the fibronectin type II domain of the SEL1L gene and possible relation to the persistent hyperinsulinemic hypoglycemia of infancy.

SEL1L, a human gene located on chromosome 14q24.3-q31, is highly expressed in adult pancreas. It is proximal to D14S67 (IDDM11) a proposed type I diabetes susceptibility locus. Considering the organ specific expression of SEL1L, a fundamental role of SEL1L in pancreatic growth can be hypothesized. While screening for mutations in young diabetic patients, in children affected by persistent hyperinsulinemic hypoglycemia of infancy (PHHI), in patients with non-functional endocrine tumours and in over 100 control subjects, we identified a novel polymorphism (D162G) residing on the fourth exon of the gene. This exon encodes for the fibronectin type II domain and the nucleotide change involves a highly conserved amino acid. The D162G polymorphism induces a major change in the amino acid composition producing a possible disruptive role in collagen binding.

Pharmacogenomics of neurodegenerative diseases.

Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.

The effect of cyclosporin A, FK506 and rapamycin on the murine contact sensitivity reaction.

We have evaluated the effects of three potent immunosuppressive agents, cyclosporin A (CsA), FK506 and rapamycin, on the murine contact sensitivity (CS) reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires participation of three distinct T cell subsets: alphabeta+, CD4+ T lymphocytes, which are the classical effector cell of the CS reaction, gammadelta+ T lymphocytes, and alphabeta+, double-negative (CD4- CD8-) T lymphocytes that express the B220 molecule and produce IL-4. We found that all three drugs inhibit the development of the CS reaction, but they affect different target cells. In fact, rapamycin and FK-506 block both alphabeta+, CD4+ and gammadelta+ T lymphocytes, while CsA inhibits only the alphabeta+, CD4+ T lymphocyte. None of the three drugs exerted any inhibitory activity on the alphabeta+, double-negative (CD4- CD8-) T lymphocytes. Hapten-immune lymph node cells from mice treated in vivo with CsA or FK506 failed to proliferate and to produce IL-2 when re-exposed to the specific antigen in vitro. In contrast, immune lymph node cells from mice that had been treated in vivo with rapamycin gave optimal antigen-specific proliferation and IL-2 production in vitro. The implications of these observations are discussed in relation to the use of these immunosuppressive agents for prevention of allograft rejection.

Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains.

Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T cell subset expressing V alpha14+ TCR alpha-chains with highly conserved invariant junctional sequences and able to secrete Th2 cytokines when exposed to CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+ TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have been recently described. Here we show that these cells (referred to as V alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in several ways. First, like their murine counterparts, T cells expressing high levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+, but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T cells are brightly stained by NKRP1-specific mAb but not by mAb directed against other type II transmembrane proteins of the NK complex. Third, DN and particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers. The concomitant expression of highly conserved TCRs of a particular set of NK markers and of Th2 cytokines in human and murine alphabeta T cells suggests a coordinate acquisition of these phenotypic and functional properties. Furthermore, the relatively high frequency of human V alpha24inv T cells, which are presently shown to represent on average 1/500 PBL, and the high interindividual variations of the size of this cell subset under physiologic conditions go for a major role played by alphabeta T cells carrying invariant TCR in a large array of immune responses.

Development of IFN-gamma-producing CD8+ gamma delta+ T lymphocytes and IL-2-producing CD4+ alpha beta+ T lymphocytes during contact sensitivity.

This paper describes the development of Ag-specific proliferation and the production of IFN-gamma and IL-2 during contact sensitivity (CS) to the hapten picryl chloride (PCl). Lymph node cells from mice immunized with PCl proliferate and produce IFN-gamma and IL-2 when re-exposed to the specific Ag in vitro. Time course experiments showed that the peak IFN-gamma production occurred at days 3 and 4 after immunization, with a sharp decline by day 6. In contrast, proliferation and IL-2 production peaked at day 3 but persisted up to day 10. Proliferation and IFN-gamma and IL-2 production displayed by immune lymph node cells were Ag-specific but required different cell populations. In fact, the production of IFN-gamma was due to a CD8+, gamma delta+ T cell, while proliferation and IL-2 production required the presence of a CD4+, alpha beta+ T cell. Furthermore, IFN-gamma production showed genetic (MHC) restriction, and finer analysis using congenic strains of mice indicated that the K molecule was the restricting element. This was confirmed by blocking the K molecule of the APC used to trigger IFN-gamma production with a specific mAb. In contrast, proliferation and IL-2 production were I-A-restricted, as demonstrated using congenic strains of mice and blocking the I-A molecule of the APCs. Further analysis using purified gamma delta+ cells revealed that these cells produced IFN-gamma in an Ag-specific and MHC (K)-restricted fashion. Injection of mice with a mAb to IL-2 blocked subsequent in vitro proliferation, as well as IL-2 and IFN-gamma production, while all three in vitro responses were unaffected by injection of a mAb to IFN-gamma given at the time of immunization. Furthermore, injection of mice with a mAb to IL-2 blocked the CS reaction when given at the time of immunization, while it had no effect when given at the time of challenge. Injection of mice with mAb to IFN-gamma at the time of challenge reduced but did not abolished CS, suggesting that IFN-gamma is important but not exclusively responsible for the CS reaction.

gamma delta cells involved in contact sensitivity preferentially rearrange the Vgamma3 region and require interleukin-7.

Ptak and Askenase showed that both alphabeta and gammadelta cells are required for transfer of contact sensitivity (CS). This study confirms that day 4 immune cells depleted of gammadelta cells fail to transfer CS to trinitrochlorobenzene (TNP-Cl) systemically and demonstrates that administration of anti-gammadelta monoclonal antibodies (mAb) in vivo abolishes the CS reaction. Moreover, gammadelta cells accumulate at the antigen challenge site: these cells have the unusual phenotype CD8alpha+, CD8beta-, IL-4 R+ which we suggest is due to their state of activation. Following immunization with contact sensitizer on the skin, the absolute number of gammadelta cells increases in the regional lymph nodes with a peak at 4 days. Of the gammadelta cells, 80 %, both in the lymph nodes of TNP-Cl-immune mice and accumulating at the antigen challenge site are Vgamma3+. The gammadelta cells expressing Vgamma3, which is characteristic of dendritic epithelial T cells (DETC), obtained 4 days after sensitization, proliferate in response to interleukin (IL)-7, but only poorly to IL-2 and IL-4. They also respond to concanavalin A and immobilized anti-gammadelta mAb, but not to haptens or heat-shocked syngeneic spleen cells. Furthermore, injection of mice with mAb to IL-7 inhibits accumulation of Vgamma3+ cells both in the lymph nodes after skin sensitization and at the antigen-challenge site. Altogether, these results strongly support the view that DETC are related to, or the original source of, the gammadelta cells found in the lymph node after skin sensitization and at the site of challenge, and that IL-7 is implicated in these phenomena.

Control mechanisms of cell-mediated reactions.

One of the most relevant aspects of tumor adoptive immunotherapy is provided by clinical trails on transfer of cytotoxic cells (LAK and TIL). However, LAK cell therapy is effective in a small number (16-22%) of only certain tumors, while therapy with TIL cells is efficient in about 40% of melanomas. Several possibilities have been raised to explain the low efficacy of cytotoxic cells in tumor therapy, amongst which are the poor immunogenicity of tumor and tumor-induced immunodepression. Furthermore, the possibility that cytotoxic cells do not reach the tumor site in adequate numbers has to be considered. We have developed an experimental system to study the ability of antigen-specific T cells to reach the target antigen in the tissues. The results obtained demonstrate that gamma delta cells and IL-4 are required to allow tissue localization of antigen-specific alpha beta cells, thus indicating that their ability to exert certain effect or functions requires cooperation by other cells types. These results may be relevant to the understanding of the mechanisms leading to localization of immunologically active cells at a tumor site.

Mutagenicity of methyl methanesulfonate and cyclophosphamide in resting and growing Saccharomyces cerevisiae D7 cells.

In order to evaluate the optimal experimental conditions and to identify the best growth phase for yeast genotoxicity studies, comparative experiments were performed with stationary and growing cells. Methyl methanesulfonate (MMS) and cyclophosphamide (CP) were used as chemical mutagens and strain D7 of Saccharomyces cerevisiae as detector of induced mitotic gene conversion (trp+ convertants) and point reverse mutation (ilv+ revertants) in log or stationary phase cells after either 4 or 16 h of treatment. The highest MMS-induced toxicity and genotoxicity were observed after 16 h of exposure in a suspension test with log phase cells, which is consistent with the greater permeability and sensitivity of growing yeast cells. The maximal induction of genetic effects and toxicity by CP was conversely obtained after 16 h of treatment in stationary phase cells. This may be ascribed to the greater ability of detoxication of growing cells as compared to resting cells. Our results suggest that in evaluating the mutagenicity of chemicals in yeast systems it is important to consider factors such as growth phase and exposure time.

[The evaluation of the presumed mutagenic activity of barium nitrate]. / Valutazione della presunta attività mutagena del bario nitrato.

Barium nitrate, which is used in industry in the production of green signal lights, to remove gases from vacuum tubes, and in the production of barium oxide, was assayed to assess the possible mutagenic effects using both the Ames test (S. typhimurium TA 1535, TA 1537, TA 1538, TA 97a, TA 98, TA 100, TA 102c), with and without metabolic activation with the plate incorporation assay and pre-incubation assay methods, and using the mitotic crossing over test, the mitotic genic conversion test, and the retromutation test in Saccharomyces cerevisiae, D7 strain, with and without metabolic activation. In the experimental conditions of the study, at various gradually increasing concentrations, barium nitrate gave negative results.

[Mutagen activity of barium chloride in Salmonella typhimurium]. / Studio dell'attività mutagena del bario cloruro in Salmonella typhimurium.

Barium chloride, which is an important industrial chemical used in pigments, lacquers, dyes, glass and pesticide production, leather tanning and cloth dying, was tested on Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 97, TA 98, TA 100) with the reverse mutation test, with and without metabolic activation, to assess its possible genotoxic effects and any possible action with respect to standard mutagens (sodium azide, 9-aminoacridine, 2-nitrofluorene, mitomycine-C, 2 aminoacridine). Using the platelet incorporation technique, barium chloride at various progressive concentrations gave negative results under the experimental conditions of the study.

[Mesotheliomas among mechanics of the railways in Italy: a current problem]. / Mesoteliomi fra i meccanici delle ferrovie in Italia: un problema di attualità.

Asbestos has been used on rolling stock of the Italian Railways since the 1940's. From the 1950's to the 1970's it was used on a massive scale for the insulation of passenger carriages (up to more than 800 kg per carriage). About 10 years ago, a programme was began to remove asbestos from rolling stock and replace it with glass fibre. We must consider as exposed to the carcinogenic effects of asbestos all mechanics who, during the past years, worked at the Major Repair Workshops (MRW), at the Locomotive Depots (LD) of the State Railways, or in other state or private factories where railway rolling stock insulated with asbestos was built, checked, repaired or demolished, or where asbestos removal operations took place. It has been estimated that the total number of mechanics potentially exposed to asbestos since 1950 in the MRWs alone amounts to more than 25,000. There are about 750 workers presently employed at the Bologna MRW and it has been estimated that the entire cohort of this MRW from the beginning of the 1950's includes about 3,000 people (in excess). In 1986 the Bologna Institute of Oncology reported 6 cases of pleural mesothelioma at the Bologna MRW and 1 at the Rimini MRW. This was the first report of pleural mesotheliomas among railway mechanics in Italy. From 1986 up to the present, other cases of pleural mesothelioma have been recorded among mechanics working on railway rolling stock in the MRW's and in the LD's of the State Railways and in other factories.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma amino acid values and pancreatic beta-cell function in phenylketonuria.

In 16 phenylketonuric (PKU) patients aged 5-12 years, plasma glucose, immunoreactive insulin (IRI), C-peptide (CP) and plasma amino acids were measured in basal conditions and under a standard oral glucose tolerance test (OGTT). The beta-cell response to OGTT was higher in PKU patients than in normal subjects as demonstrated by peak levels and areas under the curves of plasma concentrations of IRI and of CP. A significant correlation was observed between plasma phenylalanine values and both IRI and CP 'output' in PKU patients. Mean concentrations of branched chain amino acids and tyrosine in plasma decreased significantly during OGTT, while phenylalanine values increased in PKU subjects.

Human undifferentiated thyroid carcinoma synthesizes and secretes 19S thyroglobulin.

Thyroglobulin (Tg) biosynthesis and secretion have been studied in one case of undifferentiated small spindle cell human thyroid carcinoma. From tumor tissue were extracted 32 mg of soluble proteins per gram of wet tissue, compared with 54 mg from control gland; after ammonium sulfate fractionation, density gradient centrifugation, and immunoprecipitation, 1.3 mg of Tg per gram of wet tissue, compared with 31.2 mg from control, were purified. By incubating in vitro up to 3 hours tumor slices with tritiated leucine, galactose, and 125I, the rate of incorporation of leucine and galactose increased with time in tumor tissue. However 125I incorporation into soluble proteins from tumor, at 3 hours of incubation, was only 1.7% of control value. By density gradient centrifugation of labeled soluble proteins a well-separated component sedimenting in the 19S peak was identified. No radioiodine was detected in the 19S fraction which showed the immunoreactive properties of 19S and was poor in 127I and sialic acid. In the incubation medium of tumor were secreted 0.4 mg of 19S Tg per gram of wet tissue compared with 48 mg of tissue in the control gland. Thus the undifferentiated thyroid carcinoma synthesizes a protein with the physiochemical and immunologic properties of 19S Tg. The undifferentiation of thyroid cells does not affect the biochemical steps involved in the synthesis of Tg.