Matrix vesicles are enriched in metalloproteinases that degrade proteoglycans

Summary This study examined the presence of extracellular matrix processing enzymes in matrix vesicles produced by rat costochondral resting zone and growth zone chondrocytes in culture. Optimum procedures for the extraction of each enzyme activity were determined. Enzyme activity associated with chondrocyte plasma membrane microsomes was used for comparison. There was a differential distribution of the enzyme activities related to the cartilage zone from which the cells were isolated. Acid and neutral metalloproteinase (TIMP), plasminogen activator, and betaglucuronidase were highest in the growth zone chondrocyte (GC) membrane fractions when compared with matrix vesicles and plasma membranes isolated from resting zone chondrocyte (RC) cultures. There was a threefold enrichment of total and active acid metalloproteinase in GC matrix vesicles, whereas no enrichment in enzyme activity was observed in RC matrix vesicles. Total and active neutral metalloproteinase were similarly enriched twofold in GC matrix vesicles. TIMP, plasminogen activator, and betaglucuronidase activities were highest in the plasma membranes of both cell types. No collagenase, lysozyme, or hyaluronidase activity was found in any of the membrane fractions. The data indicate that matrix vesicles are selectively enriched in enzymes which degrade proteoglycans. The highest concentrations of these enzymes are found in matrix vesicles produced by growth zone chondrocytes, suggesting that this may be a mechanism by which the more differentiated cell modulates the matrix for calcification.     

Élaboration d’un guide d’information SOR SAVOIR PATIENT à l’usage des personnes malades et de leurs proches sur la vie intime et sexuelle pendant et après un cancer : l’étape d’état des lieux

Since 1998, the French National Federation of Comprehensive Cancer Centres (FNCLCC) has led an information program dedicated to patients and their relatives: the SOR SAVOIR PATIENT (SSP) program. The program is provided by the FNCLCC, the twenty French regional cancer centres (CLCC), the National League Against Cancer (LCC), the French National Cancer Institute (INCa), the French Hospital Federation (FHF), the National Oncology Federation of Regional and University Hospitals (FNCCHRU), the French Oncology Federation of General Hospitals (FFCHG), the National Private Hospital Union for Oncology (UNHPC), the International Union Against Cancer (UICC) and a large number of learned societies. The methodology of the program adheres to the quality criteria established for publishing documents containing information for patients. Issues related to the sexual health of cancer patients and their partners too often remain underestimated and even completely neglected by health professionals, although healthcare providers are increasingly interested in this area and patients frequently confront them with questions about this aspect of their lives. The development of an SOR SAVOIR PATIENT informational guide on the various issues related to sexuality during and after cancer treatment constitutes a first step in addressing the needs of cancer patients and others concerned. This article describes the first stage in the development of a specific SOR SAVOIR PATIENT guide that focuses on the general availability of informational material in French on the sexual health of patients and their partners during and after cancer treatment.     

Three-dimensional color Doppler sonography and uterine artery arteriography of fibroids: assessment of changes in vascularity before and after embolization.

OBJECTIVE: To assess the accuracy of three-dimensional color Doppler sonography and uterine artery arteriography in depicting changes in fibroid vascularity before and after embolization. METHODS: Preembolization and postembolization three-dimensional color Doppler sonography and selective uterine artery arteriography were retrospectively compared in 15 patients who underwent uterine artery embolization for treatment of symptomatic fibroids. Three-dimensional color Doppler sonography was performed by using a scanner with color power angiographic imaging capability. Vascularity was quantified by using an estimation of power-weighted pixel density as described by our group in previously published studies. Uterine artery arteriography was performed by using a standard selective microcatheter embolization technique. For purposes of comparison, fibroids were classified as either hypervascular or hypovascular relative to myometrial vascularity before and minutes to several hours after uterine artery embolization. Changes in fibroid vascularity (i.e., from hypervascular to hypovascular) as depicted by three-dimensional color Doppler sonography were compared with those shown on uterine artery arteriography and classified as being in agreement or disagreement. RESULTS: In 13 (87%) of 15 patients there was agreement; in 2 (13%) of 15 there was disagreement. In both cases of disagreement, three-dimensional color Doppler sonography showed collateral flow not depicted by uterine artery arteriography The mean reduction in quantitated vascularity after uterine artery embolization was 44% (range, 19%-78%). CONCLUSIONS: Three-dimensional color Doppler sonography accurately depicts fibroid vascularity and in some cases can reveal collateral flow not depicted by uterine artery arteriography.     

A mutation analysis of the<Emphasis Type="Italic"> BRCA1</Emphasis> gene in 140 families from southeast France with a history of breast and/or ovarian cancer

A mutation analysis of the BRCA1 gene in 140 French families with a history of breast cancer or breast-ovarian cancer revealed several deleterious germline mutations, as well as rare sequence variants. The 19 genetics variants were of 15 different types, two of which had not been reported in the Breast cancer Information Core (BIC) database. Five distinct truncating mutations, leading to putative nonfunctional proteins, were identified out of 140 index cases (3.5%). One novel nonsense mutation, C4491T, was reported, whereas the four other BRCA1 deleterious mutations identified consisted of frequent frameshifts in the nucleotide sequence. One splice variant (331+3A>G) and thirteen missense variations leading to amino acid substitutions of unknown structural and functional importance were identified. Among these, two BRCA1 missense mutations, A120G and T243C could be considered as suspected deleterious. The first missense mutation modified the initiation codon (M1V) and the second (C39R) may have consequences on the structure and functioning of the BRCA1 protein by modifying cysteine ligands from the RING finger domain. As expected BRCA1 gene alteration, including missense mutations of unknown biological significance, were more frequent in families with a history of breast-ovarian-cancer (32%) than in breast-cancer-only families (12%).     

Molecular cloning and characterization of a novel ABC transporter gene in the human pathogen Trichophyton rubrum.

A gene encoding an ABC transporter in the dermatophyte Trichophyton rubrum, TruMDR1, was cloned by PCR using degenerate primers. The open reading frame of TruMDR1 is 4838 bp long and the deduced amino acid sequence shows high homology with ABC transporters involved in drug efflux of other fungi. The effect of chemicals on the expression level of mRNAs of this gene was analysed by Northern blot. An increase in expression level was observed when the fungus was exposed to ethidium bromide, ketoconazole, cycloheximide, fluconazole, griseofulvin, imazalil and itraconazole, suggesting the participation of this gene in drug efflux in this dermatophyte. The identification of a gene potentially involved in cellular detoxification in a pathogenic fungus is the first step towards knowing molecular events related to antifungal resistance.