Effect of the spectral range of a UV lamp on the production of cyclobutane pyrimidine dimers in human skin in situ

BACKGROUND: Ultraviolet (UV) irradiation has a broad spectrum of biological effects and a capacity to initiate skin carcinogenesis through DNA damage. The effect of different wave bands of UV light on the production of DNA damage in human skin in situ was studied with a broadband UV-B lamp TL-12 and a narrowband UV-B lamp TL-01. METHODS: Eight psoriasis patients participated in the study. Their minimal erythema dose was assessed separately for the two UV-B wave band ranges. Test areas of buttock skin were irradiated with the two spectrally differing lamps using erythemally equivalent UV doses of 40 and 80 mJ/cm2 CIE (Commission International de I'Eclairage). Punch biopsies were taken from the irradiated areas, and UV-induced DNA lesions (cyclobutane pyrimidine dimers, CPDs) in the skin were analyzed with a 32P high-performance liquid chromatography postlabelling method. RESULTS: No UV source-dependent differences in the induced levels of CPDs were detected in this study. CONCLUSION: CPD production with broadband TL-12 and narrowband TL-01 UV-B lamps in situ did not differ when erythemally equivalent UV doses were used. The preliminary result needs to be confirmed in a larger study.     

Immunophenotypic changes and induction of apoptosis of monocytes and tumour cells during their interactions in vitro

The in vitro model of tumour infiltrating macrophages (TIM)-tumour interactions in which monocytes and monocyte-derived macrophages (MDM) are cultured with cancer cells was used to assess immunophenotypic changes of interacting cells. Following short cocultures, monocytes, MDM and tumour cells were sorted out by FACS and the expression of several determinants was evaluated. Monocytes showed the induction of CD44v6 and v7/8, and up-regulation of CD16 (Fc gamma RIII), CD54 (ICAM-1), CD68 (macrophage maturation marker) and CD86 (costimulatory molecule B7.2). The increased expression of CD11a (LFA-1) and CD58 (LFA-3) was noted on some cancer cells. Up-regulation of TNFRII and HLA-DR was observed on both types of cells. MDM shared similar changes. Contact of monocytes, but not of MDM, with tumour cells led to Fas-FasL-dependent apoptosis of both types of cells. This study suggests that the immunophenotype of monocytes/macrophages and cancer cells may be modified during their bidirectional interactions in the absence of other microenvironmental elements that are present in the tumour stroma.     

Middle aortic syndrome caused by Takayasu's disease and treated by stent implantation: a report of medium-term follow-up

A 13-year-old girl with middle aortic syndrome caused by Takayasu's disease was treated by balloon angioplasty of the right renal artery stenosis and the implantation of 3 stents, 2 in the stenosed thoracic segment and 1 in the abdominal segment of the aorta. Spiral computed tomography one and two years after the stents were inserted showed that the disease had progressed despite treatment with immunosuppressants.     

CYP17 genotypes differ in salivary 17-beta estradiol levels: a study based on hormonal profiles from entire menstrual cycles.

Variation in the levels of sex-steroid hormones results from differences in developmental conditions, adult lifestyle, and genetic polymorphism. Genes involved in sex-steroid biosynthesis have been implicated to influence levels of hormones in premenopausal women, but the results were inconclusive. We tested variation among women in levels of salivary estradiol (E(2)) corresponding to CYP17 genotypes. CYP17 encodes cytochrome P450c17alpha, which mediates two enzymes important in E(2) synthesis. In contrast to the earlier studies that relied on one or a few samples for assessing the E(2) levels of an individual woman, our study is based on daily collected saliva samples for one entire menstrual cycle. Sixty Polish women, ages 24 to 36 years, with regular menstrual cycles and no reported fertility problems participated in the study. Women with A2/A2 genotype had 54% higher mean E(2) levels than women with A1/A1 genotype (P = 0.0001) and 37% higher than women with A1/A2 genotype (P = 0.0008). Heterozygous A1/A2 women had 13 % higher E(2) levels than homozygous A1/A1 women (but this difference was significant only in a nonparametric test). Levels of E(2) during the day with highest E(2) (day -1) were 72% higher in A2/A2 compared with A1/A1 (P = 0.01) and 52 % higher compared with A1/A2 (P = 0.03). Our results suggest that CYP17 genotype may serve as a biomarker of endocrine function in women of reproductive age. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2131-5).     

Anosmia caused by inhaled hazardous substances. Significance for expert assessment general practice

BACKGROUND: Both environmental and occupational pollutants can affect the functional integrity of the olfactory epithelium or even destroy olfactory tissue. However, occupational hyposmia and anosmia have not been included into the list of occupational diseases. Therefore, compensation of occupationally induced smell disorders is difficult. OBJECTIVE: To evaluate patients with toxic hyposmia for the pollutants involved and to discuss consequences for occupational and environmental medicine. METHODS: A total of 19 patients were evaluated in our departments between 1993 and 1997 for olfactory disorders related to environmental or occupational pollutants. The charts of these patients were retrospectically analyzed and the causative pollutants compared with the literature. RESULTS: A chronical exposure to mixtures of metal dusts and steam, volatile organic substances, and anorganic gases were the most common pollutants involved in occupational dysosmia. Only one case of acute development of an anosmia due to exposure to CO and combustion gases was documented. CONCLUSIONS: Olfactory disorders are underestimated in occupational and environmental medicine. Relevance of olfactotoxic substances for occupational medicine can be postulated in metal and chemical workers, in welding and disinfection. The list of occupational diseases should be completed by olfactory hyposmia and anosmia.     

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.     

Mutagenicity and toxicity of the DNA alkylation carcinogens 1, 2-dimethylhydrazine and azoxymethane in Escherichia coli and Salmonella typhimurium

DNA alkylating agents such as 1, 2-dimethylhydrazine (SDMH)and azoxymethane (AOM) are potent carcinogens and are widelyused to induce colon tumors in experimental animals. However,standard bacterial mutagenesis assays have failed to detectthe mutagenic effects of these chemicals. Using derivativesof a set of Escherichia coli test strains developed by Cupplesand Miller (Proc. NatL Acad. Set USA, 86, 5345, 1989), we havedemonstrated that under two conditions, SDMH and AOM inducedpoint mutations by several-fold in a dose-dependent manner:(i) of six possible base substitutions, they only induced GC