The accuracy of MR imaging is significantly higher than that of conventional imaging in screening high-risk women. Difficulties can be caused by an atypical manifestation of hereditary breast cancers at both conventional and MR imaging and by contrast material enhancement associated with hormonal stimulation.

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by retroviral overexpression of the transcription factors Oct4, Sox2, Klf4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk for chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC, albeit at lower efficiency. To elucidate the influence of factor reduction on subsequent differentiation, we compared the efficiency of neuronal differentiation in iPSC generated from postnatal murine neural stem cells with either one (Oct4; iPSC 1F-NSC ), two (Oct4, Klf4; iPSC 2F-NSC ), or all four factors (iPSC 4F-NSC ) with those of embryonic stem cells (ESCs) and iPSC produced from fibroblasts with all four factors (iPSC 4F-MEF ). After 2 weeks of coculture with PA6 stromal cells, neuronal differentiation of iPSC 1F-NSC and iPSC 2F-NSC was less efficient compared with iPSC 4F-NSC and ESC, yielding lower proportions of colonies that stained positive for early and late neuronal markers. Electrophysiological analyses after 4 weeks of differentiation identified functional maturity in neurons differentiated from ESC, iPSC 2F-NSC , iPSC 4F-NSC , and iPSC 4F-MEF but not in those from iPSC 1F-NSC . Similar results were obtained after hematoendothelial differentiation on OP9 bone marrow stromal cells, where factor-reduced iPSC generated lower proportions of colonies with hematoendothelial progenitors than colonies of ESC, iPSC 4F-NSC , and iPSC 4F-MEF . We conclude that a reduction of reprogramming factors does not only reduce reprogramming efficiency but may also worsen subsequent differentiation and hinder future application of iPSC in cell replacement therapies.

Breast carcinoma represents the most common malignancy of women in Western countries. Despite its prevalence, the molecular mechanisms of breast cancer formation and progression are still poorly understood. Molecular studies suggest that tumoursuppressor genes involved in hereditary tumour formation may also be altered in their sporadic counterparts (Fearon, 1997). Five per cent of all patients with breast carcinomas report a family history and the majority of these familial cases have been associated with germline mutations of the BRCA1 or BRCA2 tumoursuppressor genes (Miki et al, 1994;Wooster et al, 1995). However, the BRCA1 and BRCA2 genes are not usually altered in sporadic breast carcinomas (Lancaster et al, 1996;Miki et al, 1996), although loss of heterozygosity (LOH) in the BRCA1 and BRCA2 on chromosomal arms 17q and 13q is frequently observed (Schmutzler et al, 1997).Recently, the PTEN/MMAC1/TEP1 tumour-suppressor gene has been identified on chromosomal band 10q23.3 (Li and Sun, 1997;. The product of this gene harbours a tyrosine phosphatase domain which shares high sequence homology with the cytoskeleton proteins tensin and auxilin. Mutations of PTEN were observed in a variety of tumours including breast carcinoma cell lines and primary invasive breast carcinomas . These mutations included homozygous deletions and frameshift or nonsense mutations. Moreover, loss of heterozygosity affecting 10q23.3 was detected in as many as 50% of primary breast carcinomas. Germline mutations of PTEN have been identified in Cowden disease, a rare autosomal dominant cancer syndrome characterized by malignancies of the breast, thyroid and brain . These observations point to PTEN as an interesting candidate for a tumour-suppressor gene associated with breast cancer.Recent studies on sporadic tumours demonstrated that mutations in the PTEN gene are frequent events in glioblastomas, malignant melanomas and endometrial carcinomas of the endometrioid type (Guldberg et al, 1997;Kong et al, 1997;Rasheed et al, 1997;Tashiro et al, 1997;Wang et al, 1997). In endometrial carcinomas, PTEN mutations were predominantly found in tumours with microsatellite instability (Kong et al, 1997;Tashiro et al, 1997). It remains to be shown whether the association of PTEN mutations and microsatellite instability is of biological significance. In a series of 54 sporadic breast carcinomas, two deletions resulting in truncated proteins and various missense mutations of unknown significance have been reported (Rhei et al, 1997). To further elucidate the potential role of PTEN in breast carcinomas, we analysed 103 sporadic breast carcinomas for mutations, homozygous deletions and loss of heterozygosity, and 25 families with hereditary breast cancer for constitutive mutations in the PTEN gene. MATERIALS AND METHODS Tumour specimens from sporadic breast carcinomas and blood samples from patients with hereditary breast carcinomasBreast cancer families were recruited at the University Hospital Bonn and the Department of Medical Genetics, University of Mun...

Here we report two cases of first-trimester parvovirus B19 CASE REPORTS Case 1A 32-year-old primigravida was referred to our unit after routine ultrasound examination revealed increased fetal nuchal translucency (NT) at 13 + 1 weeks' gestation. A detailed sonographic evaluation demonstrated an NT of 4.4 mm, biventricular myocardial hypertrophy, moderate skin edema, mild ascites and bilateral pleural effusion. The ductus venosus (DV) blood flow was normal (positive awave, pulsatility index for veins (PIV): 1.56) 1 . However, the measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) showed an increased velocity of 37 cm/s, suggestive of fetal anemia (Figure 1). Maternal parvovirus (PV) infection was diagnosed by determining PV-specific immunoglobulin-G (IgG) and IgM as well as PV-B19 DNA by polymerase chain reaction (PCR). Fetal karyotype was normal. Subsequently, fetal therapy by cordocentesis was offered. The placenta was located laterally. Because of the softness of the 25-G spinal needle and an inability to correct the intrauterine position, three attempts were needed to place the needle next to the umbilical cord insertion site. No paralyzing agent was used. The umbilical vein was then punctured in one attempt and 3 mL of packed red cells were transfused. The initial hemoglobin count was 0.8 g/dL. No bradycardia was observed during the procedure, which took about 2 minutes.After 2 days, decline of the MCA-PSV and complete resolution of the fetal hydrops were observed. Ultrasound and Doppler examinations were continued for a period of 10 weeks at 3-week intervals. Measurements of MCA-PSV continued to show velocities in the upper percentile range, but no additional signs of fetal anemia were detected. However, at 24 + 5 weeks' gestation the fetus presented again with severe hydrops fetalis and cardiomegaly. The measurement of MCA-PSV showed an increased velocity of 85 cm/s. Cordocentesis and intrauterine blood transfusion were performed. The initial hemoglobin count was 1.4 g/dL (reticulocytes 13.2%, thrombocytes 22/nL). PCR for PV-B19 DNA was positive in maternal blood as well as in fetal ascites and blood. Two further intrauterine blood transfusions followed (at 25 + 3 and 26 + 2 weeks' gestation) (Table 1) and finally

Idiopathic Parkinson’s disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.