Vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger.

BACKGROUND: The artery of Wollschlaeger and Wollschlaeger is a tentorial branch of the superior cerebellar artery: due to its small diameter, it is not usually seen in normal angiograms except when enlarged in the setting of a dural AVF or tentorial meningioma. Its presence has been rarely described in the Literature. CASE REPORT: herein we describe the first ever reported case of a vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger in 70 year old female patient. CONCLUSION: vermian subtentorial AVMs supplied by the artery of Wollschlaeger and Wollschlaeger are extremely rare vascular malformations. The presence of the artery of Wollschlaeger and Wollschlaeger must be carefully evaluated during preoperative surgical planning due to its key role in the supply of vascular malformation and to decrease the risk of intra operative bleeding during surgery.

Establishment and characterization of new mammary adenocarcinoma cell lines derived from double transgenic mice expressing GFP and neu oncogene.

A new murine cell line, named GFPneu, was established from a mammary adenocarcinoma arising in double transgenic MMTVneu x CMV-GFP mice. Breast tumours develop in 100% of females after 2 months latency, as a result of the over-expression of the activated rat neu oncogene in the mammary glands. All tissues, and in particular the breast tumours, express the GFP protein. This cell line was tumorigenic when inoculated into nude mice and the derived tumours showed the same histological features as the primaries from which they were isolated. Their histopathology reproduces many characteristics of human breast adenocarcinomas, in particular their ability to metastasize. The GFP marker allows us to visualize the presence of lung metastases in fresh tissues immediately, to confirm the histopathology. From a lung metastatic fluorescent nodule, we derived a further cell line, named MTP-GFP, which we also characterized. These two cell lines could be useful to study the role played by the neu oncogene in the maintenance of the transformed phenotype, in the metastatic process, to test novel therapeutic strategies to inhibit primary tumour growth and to observe the generation of distant metastases.

Association between a polymorphism affecting an AP1 binding site in the promoter of the TCIRG1 gene and bone mass in women.

The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine ( P = 0.01) and femoral neck ( P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking ( P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 "G" allele had BMD values significantly higher than individuals who carried the -1100 "A" allele at both spine ( P = 0.007) and hip ( P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6% of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.

The mutational spectrum of human malignant autosomal recessive osteopetrosis.

Human malignant infantile osteopetrosis (arOP; MIM 259700) is a genetically heterogeneous autosomal recessive disorder of bone metabolism, which, if untreated, has a fatal outcome. Our group, as well as others, have recently identified mutations in the ATP6i (TCIRG1) gene, encoding the a3 subunit of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, are responsible for a subset of this condition. By sequencing the ATP6i gene in arOP patients from 44 unrelated families with a worldwide distribution we have now established that ATP6i mutations are responsible for approximately 50% of patients affected by this disease. The vast majority of these mutations (40 out of 42 alleles, including seven deletions, two insertions, 10 nonsense substitutions and 21 mutations in splice sites) are predicted to cause severe abnormalities in the protein product and are likely to represent null alleles. In addition, we have also analysed nine unrelated arOP patients from Costa Rica, where this disease is apparently much more frequent than elsewhere. All nine Costa Rican patients bore either or both of two missense mutations (G405R and R444L) in amino acid residues which are evolutionarily conserved from yeast to humans. The identification of ATP6i gene mutations in two families allowed us for the first time to perform prenatal diagnosis: both fetuses were predicted not to be affected and two healthy babies were born. This study contributes to the determination of genetic heterogeneity of arOP and allows further delineation of the other genetic defects causing this severe condition.

[Association of systemic sclerosis and psoriatic arthritis: a case report] / Associazione sclerosi sistemica ed artrite psoriasica: descrizione di un caso clinico.

The association of Systemic Sclerosis (SSc) and Psoriatic Arthritis (PsA) is unfrequent; only few cases are reported in literature. We describe a case of a patient with SSc following the onset of PsA. The disease begun with tenosynovitis, polyarthritis in association with psoriasis. After two years, Raynaud's phenomenon and sclerodactyly appeared, and, later, pulmonary interstitial fibrosis and esophageal dysfunction. The existence of a common pathogenesis of the two diseases, SSc and PsA, is discussed.

Distribution of interstitial telomere-related sequences in the human genome and their relationship with fragile sites.

Using a computer search in the mapped human genome, we could show that interstitial telomere-related sequences are clustered in R-bands, and, in some cases, coexist with mapped fragile sites. We speculate that this association could predispose to chromosome fragility and recombination.

Cycling-PRINS. A method to improve the accuracy of telomeric sequence detection in mammalian chromosomes.

The presence of (TTAGGG)n telomeric sequence was investigated in a Chinese hamster tumor-derived cell line, using single primed in situ labelling (single-PRINS) and multiple cycles of amplification (cycling-PRINS). The telomeric sequence hybridized the centromere of most chromosomes, using both techniques. However, signals visible at the telomeric regions of some chromosomes and an enhancement of the frequency signals at the centromere of chromosome 1 were obtained using cycling-PRINS. These results indicate that cycling-PRINS represents a promising improvement for detection of telomeric sequence in cell lines where the conventional methods failed to demonstrate their presence.

Assignment of Chinese hamster p53 gene (TP53) to chromosome band 2p31, a region not involved in the karyotypic changes of a tumorigenic cell line.

The Chinese hamster tumor-derived cell line 835T2 exhibits specific karyotypic changes, including the loss and/or translocation of genetic material. To investigate whether the p53 tumor suppressor gene was involved in the exchanges, cDNA from primary Chinese hamster cells was isolated by using sense and antisense primers of the human p53 gene. The cDNA was sequenced, and the sequence was compared with the Syrian and human p53 cDNA reported sequences. The sequence homology was very elevated, demonstrating that the cloned fragment contained part of the Chinese hamster p53 gene. The corresponding genomic fragment was also cloned and used as a biotin-labeled probe for in situ hybridization on Chinese hamster chromosome spreads. Hybridization was visualized by avidin-FITC, and the assignment was done comparing the banding obtained with BamHI restriction enzyme and the location of the fluorescent signals pattern of the same metaphase. The signals revealed that the p53 gene (TP53) is localized on Chinese hamster chromosome band 2p31, which is not involved in the karyotypic changes specific to the 835T2 cell line.

Aphidicolin-sensitive specific common fragile sites: a biomarker of exposure to pesticides.

In this work, we analyzed the aphidicolin-sensitive common fragile sites in seven females and four males occupationally exposed to pesticides and in ten controls. The same males had been monitored one year earlier in a previous study by the same authors. Results showed enhanced expression in exposed subjects at eight bands, namely, 6q25, 7p22, 7q22, 7q32, 13q14, 14q24, 16q22, and 16q23. Most of these bonds were fragile sites and breakpoints involved in chromosome rearrangements found in hematopoietic tumors. Moreover, six of these bands were already detected, with enhanced expression, in the first monitoring carried out on male subjects. These results indicated that fragile sites analysis is a reproducible cell response to human exposure to pesticides.

Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)n telomeric sequence in Chinese hamster cells.

Aphidicolin-sensitive fragile sites were analyzed in immortalized Chinese hamster embryonal fibroblast cells (CHEF18) at three different passages along their spontaneous progression toward tumorigenicity. Five fragile sites (viz., 12q22, 3cen, 3p21, 3q31, and Xq21) were detected. Three of these sites carry spontaneous aberrations and are thus regions of chromosomal instability; however, they were not involved in the formation of the clonal rearrangements that are characteristic of CHEF 18 cells. The presence of the (TTAGGG)n telomeric sequence in chromosome bands associated with fragile sites was investigated using fluorescence in situ hybridization and primed in situ labeling. A common location of fragile sites and telomeric sequence was found at the centromere of chromosome 3.

No statistical association between fragile sites and constitutional chromosome breakpoints.

Ten thousand four hundred ninety-two constitutional breakpoints available from the cytogenetic literature were analyzed for their coincidence with known fragile sites (FS) at 303-band resolution. In this analysis we have taken into account the stochastic connections of some features of chromosome bands with both the presence of FS and constitutional breakage. Our results suggest that there is no particular association between FS and constitutional chromosome rearrangements.

Enhanced expression of common fragile site with occupational exposure to pesticides.

The expression of common fragile sites (FS), induced by aphidicolin, in subjects with occupational history of exposure to pesticides has been studied. Results showed a higher frequency of FS in exposed subjects; in particular, there was an elevated expression of FS at the cancer breakpoints 3p14, 5q31, 7q22, 7q32, 14q24, and 16q22, involved in leukemias and non-Hodgkin's lymphoma. Moreover, the frequency of breaks in chromosomal bands carrying oncogenes or tumor suppressor genes involved in aberrations was significantly higher in exposed subjects at sites 1q25, 3p25, 7p22, 8q24.1, and 13q14.

Specific chromosomal aberrations correlated to transformation in Chinese hamster cells.

Cytogenetic changes were investigated during the spontaneous progression of CHEF18 Chinese hamster cells towards tumorigenicity. We further report the chromosomal characterization of a series of spontaneous anchorage-independent clones, as well as of a series of tumor-derived cell lines resulting from injection of late passage cells in nude mice. The high karyotypic homogeneity (presence of four marker chromosomes strictly associated in all the metaphases analyzed) in all clones and tumor-derived cell lines prompted us to alter the specific pattern of chromosomal aberrations in order to identify which if any of the aberrations were more strictly related to transformation. For this purpose we treated a tumor-derived cell line with Colcemid and analyzed the reversion of anchorage-independent phenotype in the subclones showing an altered association of the four marker chromosomes. We conclude that two of four marker chromosomes contribute to anchorage independence.