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Biomedical subjects

S Signorini

Publications and source records attributed to S Signorini.

28 records · Page 2Linked to original sources
PubMed1997

Oligoclonal CD4+ CD57+ T-cell expansions contribute to the imbalanced T-cell receptor repertoire of rheumatoid arthritis patients.

A peculiar feature of rheumatoid arthritis patients is that they carry clonally expanded CD4+ and CD8+ cells in the peripheral blood. While the distortion of the repertoire of CD8+ cells has been ascribed to the increase of CD8+ CD57+ large granular lymphocytes, often detected in these patients, the mechanism responsible for the clonal expansion of CD4+ cells remains unexplained. Here, we report that CD4+ CD57+ cells, that in healthy individuals represent a small subset of peripheral CD4+ lymphocytes, are significantly expanded in the peripheral blood of a considerable percentage of rheumatoid arthritis patients. Furthermore, the expansion of these lymphocytes appears to correlate with the presence of rheumatoid factor. The molecular analysis of the T-cell receptor variable beta segments expressed by the CD4+ CD57+ cells enriched in rheumatoid arthritis patients showed that they use restricted repertoires, that partially overlap with those of their CD4- CD57+ counterpart. The structural feature of the receptor ligand expressed by these cells revealed that their expansion is most likely mediated by strong antigenic pressures. However, since we also found that CD4+ CD57+ and CD4- CD57+ cells can share the same clonal specificity, it is likely that their selection is not mediated by conventional major histocompatibility complex restricted mechanisms. Thus, while our data demonstrate that CD4+ CD57+ cells play an important role in establishing the imbalance of the CD4+ cell repertoire observed in rheumatoid arthritis patients, they also suggest that these cells have common features with mouse CD4+ CD8- NK1.1+/T cells.

Amino Acid Sequence↗
PubMed1997

Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.

G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of G protein-coupled receptors for neurotransmitters and hormones and may play an important role in the regulation of neuronal excitability. GIRK channels may be important in neurodevelopment, as suggested by the recent finding that a point mutation in the pore region of GIRK2 (G156S) is responsible for the weaver (wv) phenotype. The GIRK2 G156S gene gives rise to channels that exhibit a loss of K+ selectivity and may also exert dominant-negative effects on G(betagamma)-activated K+ currents. To investigate the physiological role of GIRK2, we generated mutant mice lacking GIRK2. Unlike wv/wv mutant mice, GIRK2 -/- mice are morphologically indistinguishable from wild-type mice, suggesting that the wv phenotype is likely due to abnormal GIRK2 function. Like wv/wv mice, GIRK2 -/- mice have much reduced GIRK1 expression in the brain. They also develop spontaneous seizures and are more susceptible to pharmacologically induced seizures using a gamma-aminobutyric acid antagonist. Moreover, wv/- mice exhibit much milder cerebellar abnormalities than wv/wv mice, indicating a dosage effect of the GIRK2 G156S mutation. Our results indicate that the weaver phenotypes arise from a gain-of-function mutation of GIRK2 and that GIRK1 and GIRK2 are important mediators of neuronal excitability in vivo.

Animals↗
PubMed1996

Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)

The disease maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM), characterized by early onset, usually before 25 years of age and often in adolescence or childhood, and by autosomal dominant inheritance. It has been estimated that 2-5% of patients with NIDDM may have this form of diabetes mellitus. Clinical studies have shown that prediabetic MODY subjects have normal insulin sensitivity but suffer from a defect in glucose-stimulated insulin secretion, suggesting that pancreatic beta-cell dysfunction rather than insulin resistance is the primary defect in this disorder. Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 (MODY1), 7 (MODY2) and 12 (MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. Here we show that MODY1 is the gene encoding HNF-4alpha (gene symbol, TCF14), a member of the steroid/thyroid hormone receptor superfamily and an upstream regulator of HNF-1alpha expression.

Adult↗
PubMedDate not supplied

[Vaccine prophylaxis: contribution for the control of biologic risk in exposed workers].

Working activities with exposure to biological agents have become a matter of discussion especially after the introduction in Italy of the Law 626/94, in conformity with the EU directive 90/679/EEC. There are many important biological agents that can have infectious, allergic, toxic or carcinogenic effects on the working population. Large occupational groups are exposed to these biohazards, both in agriculture and industry. Vaccination is one of the most beneficial medical practices, which has led to the eradication of such a devastating human disease as smallpox and the almost total elimination of poliomyelitis. Vaccination is also one of the most cost effective prevention measures applicable in this respect. This paper describes the possible vaccinations that employers should make available to employees exposed to biological risk, according to article 86 of Law 626/94.

Containment of Biohazards↗
PubMedDate not supplied

[Delphi study in the identification of research need in occupational medicine in Italy].

The aim of the study was to identify the research priorities and strategies in Occupational Safety and Health (OSH) in Italy with a high degree of consensus. Based on the Delphi technique, a two-phase questionnaire was sent to experts at Universities, Local Health Units (ASLs) and Trade Unions. In the first phase, experts were requested to indicate three research topics in the OSH sector. A total of 27 topics for both universities and ASLs and 18 topics for Trade Unions were identified. In the second phase, experts were requested to assign a score from one (low relevance) to five (high relevance) to each topic previously identified. On the basis of a mean score reported for each topic, two ranked lists of priorities, one referred to universities and ASLs the other referred to Trade Unions, were formulated. The highest priority identified by universities and ASLs was occupational carcinogenesis, followed by quality in occupational medicine. Workers' information, education and participation was also identified with a high degree of priority. For Trade Unions, occupational cancers as well as training, information, participation and prevention awareness had the highest priority. Trade Unions also identify small-industries and occupational accidents as topics with high priority for research development. This study allowed a high degree of consensus to be reached regarding the research priorities in the OSH sector in Italy. Differences in the topics identified, or regarding the mean score of topics commonly identified, were related to the origin of the expert recruited to this study (University, ASLs or Trade Unions) and, for universities and ASLs, to the geographical area. In the authors' opinion, the full transfer of existing scientific data to occupational health practice and the harmonization of the priorities identified by this investigation are crucial if the research needs in the OSH sector in Italy are to be met.

Delphi Technique↗
PubMedDate not supplied

[Health risk caused by exposure to low-dose chemical agents at research laboratories].

In literature there are many works on the exposure to organic solvents and its risk. In research laboratories the risk valuation is really problematic due to different variables such as low dose, multiple exposure to substances with different characteristic of hazardous. We analyzed the blood exams of workers of seven biomedical research laboratories for finding a correlation between exposition and the variability of some parameters.

Adult↗
PubMedDate not supplied

[SARS and occupational risk].

SARS is an infectious disease caused by a previously unrecognized human coronavirus, called SARS-associated coronavirus (SARS-CoV). Current information indicates that most transmission is via respiratory droplets coming from a person who is symptomatic with SARS ("close contact"). The aim of our study is to evidence the critical role of the family physician, the first health-care worker who cares with suspected/probable SARS patients, underlying the importance of the correct use and management of the personal protective equipment.

Humans↗
PubMedDate not supplied

[Occupational exposure to endocrine disruptors: state of the art].

Research into how exposure to "endocrine disrupters chemicals" affects human health is attracting increasing attention among European and international scientists since these contaminants are so widespread in the home and work environment and can have far-reaching effects on mental and physical health. Here we draw a general picture of studies to date on specific occupational exposures to single chemicals such as bisphenol A, styrene, etc., or homogeneous groups such as pesticides, metals, dioxins, phthalates and others. Although the exposure occurs in different ways, the toxic mechanisms of action vary widely, and it is hard to establish precisely the conditions of occupational exposure, significant correlations are nevertheless evident between the potential dose and its effects and further studies are certainly needed. There is still much debate on the epidemiological methods employed, which may overestimate exposure. The "measure" or at least an accurate description of exposure conditions is critical to the whole question and attempts to ensure this involve standardized procedures and statistical tests as the basis for a protocol for assessing the risk of occupational exposure. Investigations to date have focused on the effects on the reproductive system, in males in particular. However, considering the broad range of equilibria and systems on which endocrine destructive compounds can act, the international scientific community needs to persist in its efforts to develop methods for checking the effects on other endocrine organs--particularly the thyroid gland--and on the immune and neurological systems.

Adult↗
PubMedDate not supplied

Serum dioxin levels in Seveso, Italy, population in 1976.

On July 10, 1976, an explosion at a chemical plant near Seveso, Italy, released a mixture of chemicals, including 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,4,5-trichlorophenol. As a result, several thousand people in the Seveso area may have been exposed to those chemicals. At that time, human exposure assessment was based primarily on soil levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Medical examinations of this potentially exposed population and control subjects were begun in 1976 and in some cases continued until 1985. In 1988, we began assessing human exposure in this population by measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in small volumes of serum specimens remaining from the medical examinations. As expected, we found that the median serum dioxin levels were highest among people who lived closest to the explosion and were progressively lower among groups living farther away. These measurements have allowed us to assess exposure more accurately among individuals in this population and to relate exposure to various health effects. We found that some individuals in the exposed population had among the highest serum dioxin levels ever reported, yet chloracne was the only unequivocal effect found; cancer risks are still being investigated. We also found that other individuals with as high or higher serum dioxin levels did not develop chloracne. We also found that the serum half-life of dioxin in this population was 7-8 years, which agrees with other findings although we do report some differences in the serum half-life of TCDD for women and children. We also observed an increase in the percentage of female newborns to parents who resided in Zone A at the time of the explosion, and we also report on the 1976 serum dioxin levels in people who later developed cancer.

Accidents↗