Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Immune reactions associated with silicone-based ventriculo-peritoneal shunt malfunctions in children

The implantation of ventriculo-peritoneal (VP) shunting systems is the most commonly performed neurological procedure in children with hydrocephalus. Although the overall complication risk is low, the cumulative risk of shunt failure is high and unfortunately results in a high prevalence of revision surgeries. In this study, we explored the concept that some pediatric patients may develop an immune response to either the proteins attached to the silicone implant surface or to the biomaterial itself, and that this reaction may contribute to VP shunt failure in some individuals. The data displays that the sterile shunt malfunction group had a higher rate of protein deposition and increased levels of autoantibodies to the extracted surface proteins as compared to individuals with functioning shunting systems. The precise nature of the shunt-bound proteins that serve as antigens in this experiment have not yet been determined. The data also indicated that some individuals develop antibodies to polymeric substances that cross-react with partially polymerized acrylamide. The detection of significant amounts of shunt-bound protein, antibody responses to these proteins and to polymeric substances suggest that an immunological response to these proteins may play a role in the mechanism behind sterile shunt malfunctions.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Structure-function studies of the C3a-receptor: C-terminal serine and threonine residues which influence receptor internalization and signaling

The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-terminal serine (Ser) or threonine (Thr) residues, which may represent putative phosphorylation sites to characterize their role in ligand-induced C3aR internalization and signaling. Ser475/479 and Thr480/481 as well as Ser449 seemed not to be involved in ligand-induced receptor internalization. Either directly or by a conformational change they even "inhibit" C3aR internalization. In contrast, mutants with Ala substitutions at Ser465/470 and Thr463/466 were poorly internalized, and Thr463 seemed to be the most important C-terminal Thr or Ser residue directly effecting receptor internalization. However, it is likely that other C3aR regions additionally participate in this negative feed-back mechanism since even mutants with multiple Ala substitutions still internalized to a limited degree. Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling.     

Vitamin D-Stoffwechsel und Niereninsuffizienz

Zusammenfassung Es wurden Untersuchungen über den Langzeitmetabolismus von Vitamin D bei Normalpersonen und Patienten mit Niereninsuffizienz durchgeführt. Nach intravenöser Injektion von Vitamin D₃-H₃ zeigte sich in den untersuchten Serumproben weder für die Halbwertszeit noch für die Verteilung von Vitamin D und seinen verschiedenen Metaboliten ein Unterschied zwischen den beiden Gruppen. Diese Untersuchungsergebnisse machen es sehr unwahrscheinlich, daß eine Vitamin D-Stoffwechselstörung für die Entwicklung der azotämischen Osteopathie verantwortlich ist.

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Summary Investigations have been performed in normal subjects and renal patients on the long term metabolism of vitamin D₃. After an intravenous injection of tritiated vitamin D₃ there was no difference between both groups: halflife and the distribution of vitamin D and its various metabolites in the serum were almost identical. Our results suggest that a disorder of vitamin D metabolism is not responsible for the development of the azotemic osteodystrophy.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Improved In Vitro Excystation Procedure for Giardia lamblia Cysts

Giardia lamblia cysts obtained from human symptomatic and asymptomatic donors were excysted in vitro. Excystation averaged 87% for cysts from symptomatic donors and 70% for cysts from asymptomatic donors.     

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.      

Neurosurgical anatomy of the anterior interhemispheric approach for aneurysms of the anterior communicating artery (26.6.92)

Summary The anterior interhemispheric approach for aneurysms of the anterior communicating artery was studied in ten cadavers. This approach presents several advantages over the pterional approach widely used in neurosurgery. It allows direct access to the region of the anterior communicating artery complex with minimal retraction of the brain and preservatioin of the olfactory tract and the gyrus rectus.

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Bases anatomiques de l'abord inter-hémisphérique antérieur lors de la chirurgie des anévrysmes de l'artère communicante antérieure

Résumé Ce travail concerne l'abord neurochirurgical des anévrysmes de l'artére communicante antérieure par voie frontale interhémisphérique. L'étude anatomique a été réalisée sur dix sujets. Cette exposition possède de nombreux avantages comparée à la voie ptérionale habituelle : voie d'abord reduite médiane permettant une visualisation directe et symétrique du complexe artériel de l'artére communicante antérieure ; avec le moindre manipulation et retraction du cerveau en respectant les voies olfactives et le gyrus rectus.