Monozygotic twins discordant for trisomy 18.

We report on the pre- and postnatal cytogenetic, molecular genetic and clinical findings in monochorionic-diamniotic twins discordant for trisomy 18. Structural anomalies were identified in one of the twins on prenatal ultrasound examination at 20 weeks' gestation and sampling of amniotic fluid from both sacs was performed for karyotyping. This revealed trisomy 18 in the twin with abnormalities and a normal karyotype in the other twin. Elective Cesarean section was performed at 31 + 5 weeks and the aneuploid twin died shortly after delivery. The surviving twin showed low-grade mosaicism for trisomy 18 on postnatal analysis but has shown normal development. For prenatal diagnosis in monochorionic-diamniotic twin pregnancy the sampling of both amniotic sacs is recommended, especially if one twin has structural anomalies on ultrasound scan.

[H1N1--pregnancy as risk factor]. / H1N1 - Risikofaktor Schwangerschaft.

There have been repeated reports of a particularly severe course of disease on H1N1 infection in pregnant women. Complemented by a review of the current literature, this paper gives an overview of recommendations with respect to vaccination, therapy and prophylaxis in this risk group.

[Detection of microcalcifications by high-resolution B-mode sonography in patients with BI-RADS 4a lesions]. / Nachweis von Mikrokalk durch hochauflösende B-Mode-Sonographie bei BI-RADS-4a-Patientinnen.

OBJECTIVE: Evaluation of the diagnostic quality of high-resolution B-mode sonography for the detection of microcalcifications and calcification-associated focal findings in patients with BI-RADS lesions of subtype 4a. PATIENTS AND METHODS: 40 patients underwent X-ray mammography and 13-MHz B-mode sonography. The following parameters were examined: with X-ray mammography: extent of microcalcification and visibility of associated focal areas; with ultrasound: sensitivity of microcalcification findings, quality of presentation, extent of microcalcification, visibility of associated focal areas and feasibility of ultrasound-assisted biopsy. RESULTS: X-ray mammography showed a mean extent of microcalcification of 28 8 21 mm. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and accuracy of microcalcification-associated focal findings were 61.5, 57.9, 50, 45.8 and 47.5%. B-mode sonography achieved a sensitivity of 100%. Sonographically, the mean extent of microcalcification was 7 +/- 3 mm and thus significantly smaller (p < 0.01). Sensitivity, specificity, PPV, NPV and accuracy were 14.3, 84.2, 50, 47.1 and 47.5%. Ultrasound-assisted biopsy appeared feasible in 22 patients (55%). CONCLUSION: High-frequency B-mode sonography allows a highly sensitive confirmation of microcalcifications in the case of BI-RADS 4a lesions and seems to allow ultrasound-assisted biopsy in about half the patients.

Molecular and biochemical evidence for the involvement of the Asp-333-His-523 pair in the catalytic mechanism of soluble epoxide hydrolase.

In order to investigate the involvement of amino acids in the catalytic mechanism of the soluble epoxide hydrolase, different mutants of the murine enzyme were produced using the baculovirus expression system. Our results are consistent with the involvement of Asp-333 and His-523 in a catalytic mechanism similar to that of other alpha/beta hydrolase fold enzymes. Mutation of His-263 to asparagine led to the loss of approximately half the specific activity compared to wild-type enzyme. When His-332 was replaced by asparagine, 96.7% of the specific activity was lost and mutation of the conserved His-523 to glutamine led to a more dramatic loss of 99.9% of the specific activity. No activity was detectable after the replacement of Asp-333 by serine. However, more than 20% of the wild-type activity was retained in an Asp-333-->Asn mutant produced in Spodoptera frugiperda cells. We purified, by affinity chromatography, the wild-type and the Asp-333-->Asn mutant enzymes produced in Trichoplusia ni cells. We labeled these enzymes by incubating them with the epoxide containing radiolabeled substrate juvenile hormone III (JH III). The purified Asp-333-->Asn mutant bound 6% of the substrate compared to the wild-type soluble epoxide hydrolase. The mutant also showed 8% of the specific activity of the wild-type. Preincubation of the purified Asp-333-->Asn mutant at 37 degrees C (pH 8), however, led to a complete recovery of activity and to a change of isoelectric point (pI), both of which are consistent with hydrolysis of Asn-333 to aspartic acid. This intramolecular hydrolysis of asparagine to aspartic acid may explain the activity observed in this mutant. Wild-type enzyme that had been radiolabeled with the substrate was digested with trypsin. Using reverse phase-high pressure liquid chromatography, we isolated four radiolabeled peptides of similar polarity. These peptides were not radiolabeled if the enzyme was preincubated with a selective competitive inhibitor of soluble epoxide hydrolase 4-fluorochalcone oxide. This strongly suggested that these peptides contained a catalytic amino acid. Each peptide was characterized with N-terminal amino acid sequencing and electrospray mass spectrometry. All four radiolabeled peptides contained overlapping sequences. The only aspartic acid present in all four peptides and conserved in all epoxide hydrolases was Asp-333. These peptides resulted from cleavage at different trypsin sites and the mass of each was consistent with the covalent linkage of Asp-333 to the substrate.