In order to estimate the contribution of mutations at the fibrillin-1 locus (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic differences between patients with an FBN1 mutation vs. without, a comprehensive molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the clinical diagnosis of MFS according to the Ghent nosology was performed. The initial mutation screening by CSGE/SSCP allowed identification of an FBN1-mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11 mutation-negative patients, while in nine others, DHPLC was used. This allowed identification of seven and five additional mutations, respectively. Southern blot analysis revealed an abnormal hybridization pattern in one more patient. A total of 23 out of the 85 mutations identified here are reported for the first time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs. premature termination mutations revealed significant differences in ocular and skeletal involvement. The phenotype of the eight patients without proven FBN1 mutation did not differ from the others with respect to the presence of major cardiac, ocular, and skeletal manifestations or positive familial history. Most likely, a portion of FBN1-mutations remains undetected because of technical limitations. In conclusion, the involvement of the FBN1-gene could be demonstrated in at least 91% of all MFS patients (85/93), which strongly suggests that this gene is the predominant, if not the sole, locus for MFS.
Aims: To investigate the occurrence of preinvasive neoplastic lesions in ovarian surface epithelium and ovarian inclusion cyst epithelium of women with a hereditary predisposition to the development of female adnexal (ovarian and fallopian tube) carcinoma and to assess the expression of differentiation and proliferation related proteins within putative sites of origin of serous ovarian carcinoma, the ovarian surface epithelium and ovarian inclusion cyst epithelium. Methods: Twenty‐one ovaries, prophylactically removed from 11 women predisposed to the development of female adnexal cancer (cases) were compared with 22 ovaries from 11 women without such predisposition (controls). Archival histological specimens were screened for hyperplastic and dysplastic epithelial lesions. In both the ovarian surface and inclusion cyst epithelia, the percentage of cells was determined that stained positively for Ki67, p21, p27, p53, cyclin A, cyclin D1, bcl‐2 and the presence of HER‐2/ neu , oestrogen (ER‐α) and progesterone receptors (PR). Results: No preinvasive neoplastic lesions were detected. However, hyperplastic areas were found in three cases and in four controls (NS). ER‐α ( P = 0.013), PR ( P < 0.001), bcl‐2 ( P = 0.008), p21 ( P = 0.046) and p27 ( P = 0.008) were expressed in a significantly higher percentage of cells in inclusion cyst epithelium than in ovarian surface epithelium (both groups). The latter showed higher bcl‐2 expression in cases ( P = 0.05) compared with controls. The inclusion cyst epithelium of cases showed higher expression of bcl‐2 ( P = 0.006) and PR ( P = 0.039) compared with controls. Proliferation was low in both cases and controls as reflected by low Ki67 expression. Over‐expression of p53, cyclin D1 and HER‐2/ neu was not detected. Conclusions: Premalignant changes are not a common feature of ovaries removed prophylactically from women predisposed to the development of female adnexal carcinoma. Increased expression of p21, p27, and ER‐α is seen in inclusion cyst compared with ovarian surface epithelium of women with and without an inherited risk of adnexal carcinoma. This is most probably caused by the different intraovarian hormonal milieu of inclusion cyst epithelium. However, the increased expression of bcl‐2 and PR in the inclusion cyst epithelium of patients with a hereditary predisposition may reflect early disruption of hormonal balance and growth control.
Two unrelated children with Marfan syndrome presented with recurrent intracranial hypertension. Both children complained of headache, nausea, and vomiting and one of them had papilledema. Both had increased cerebrospinal fluid pressure, and their complaints disappeared after lumbar puncture. Although severe headache has been reported in Marfan syndrome due to intracranial hypotension, this is to our knowledge the first report of intracranial hypertension in Marfan patients.
The aims of this work are to isolate bacterial symbionts from nudibranchs and subsequently to determine anti-Methicillin resistant Staphylococcus aureus (MRSA), cytotoxicity and anti-Herpes simplex virus type 1 (HSV-1) activities of bio compounds. A total of 15 species of nudibranchs were collected from Karimunjawa and five species from Bali, respectively. A total of 245 bacteria isolates were obtained. The anti-MRSA activity screening activity indicated two active bacteria. Ethyl acetate extracts from supernatants, indicating extracelullar compounds, showed an inhibition zone against MRSA at concentrations of 500–1,000 µg/ml. DNA sequence analysis showed that the strain KJB-07 from Phyllidia coelestis was closely related to Pseudoalteromonas rubra , whereas the strain NP31-01 isolated from Phyllidia varicosa was closely related to Virgibacillus salarius . The extract of Pseudoalteromonas rubra was cytotoxic to Vero cells at a concentration of 75 µg/ml. The extract of V. salarius presented no cytotoxicity at concentrations of 5–1,000 µg/ml. No anti HSV-1 was observed for both isolated bacteria. This is the first study describing research on anti-MRSA, cytotoxicity and anti HSV-1 activity of bacterial symbionts from the viscera of nudibranch. Compounds produced by Pseudoalteromonas rubra and V. salarius , had potential anti-MRSA activity. However, only extracts from Pseudoalteromonas rubra showed cytotoxic effects on Vero cells. Three compounds were identified by LC/MS after purification from culture supernatant.
