Crossreactivity of an Antiserum Directed to the Gram-Negative Bacterium Neisseria gonorrhoeae with the SNARE-Complex Protein Snap23 Correlates to Impaired Exocytosis in SH-SY5Y Cells.

Early maternal infections with Neisseria gonorrhoeae (NG) correlate to an increased lifetime schizophrenia risk for the offspring, which might be due to an immune-mediated mechanism. Here, we investigated the interactions of polyclonal antisera to NG (α-NG) with a first trimester prenatal brain multiprotein array, revealing among others the SNARE-complex protein Snap23 as a target antigen for α-NG. This interaction was confirmed by Western blot analysis with a recombinant Snap23 protein, whereas the closely related Snap25 failed to interact with α-NG. Furthermore, a polyclonal antiserum to the closely related bacterium Neisseria meningitidis (α-NM) failed to interact with both proteins. Functionally, in SH-SY5Y cells, α-NG pretreatment interfered with both insulin-induced vesicle recycling, as revealed by uptake of the fluorescent endocytosis marker FM1-43, and insulin-dependent membrane translocation of the glucose transporter GluT4. Similar effects could be observed for an antiserum raised directly to Snap23, whereas a serum to Snap25 failed to do so. In conclusion, Snap23 seems to be a possible immune target for anti-gonococcal antibodies, the interactions of which seem at least in vitro to interfere with vesicle-associated exocytosis. Whether these changes contribute to the correlation between maternal gonococcal infections and psychosis in vivo remains still to be clarified.

Etilefrinhydrochloride tablet ingestion: successful therapy by endoscopic removal of tablet conglomerate.

We report here on a case of etilefrinhydrochloride tablet intoxication in suicidal intention in a female adolescent. Tablet ingestion resulted in the formation of a tablet conglomerate in the stomach, which could neither be effectively treated with activated charcoal nor by gastric lavage. Endoscopic dissemination and removal of the fragments finally led to the elimination of the tables and the symptoms of intoxication resolved completely. The case presented here offers an explanation as to why the use of activated charcoal and/or a gastric lavage may not be successful in some cases of ingestion/intoxication. Endoscopic removal of ingested fragments of the toxic substance, such as etilefrinhydrochloride tablets, may be useful even hours following ingestion and should be considered when treatment with activated charcoal or gastric lavage fail to eliminate toxic substances in cases of tablet ingestion.

[Gianotti-Crosti syndrome in an infant following immunization]. / Gianotti-Crosti-Syndrom nach Impfungen bei einem Kleinkind -- Fallbericht und Ubersicht der Literatur.

Gianotti-Crosti syndrome (GCS), first described by F. Gianotti in 1955, was originally reported to be associated with hepatitis B virus infection in children. The typical clinical picture allows diagnosis of GCS at first glance. The pathogenesis is still unknown. Besides HBV infection, a large number of infectious agents, mostly viruses, have been described as a trigger of GCS. Here we report the occurrence of GCS in an infant five days after the fourth immunization against poliomyelitis, DTPa, Hib, hepatitis B and Streptococcus pneumoniae. Our data and review of the literature suggest that GCS is rarely associated with immunizations, especially when performed with inactivated vaccines.

Targets of activated steroid hormone receptors: basal transcription factors and receptor interacting proteins.

Steroid hormone receptors constitute a family of inducible transcription factors that mediate the multi-fold effects of steroids on development, reproduction, proliferation, and cellular homeostasis. Activation through the binding of the cognate hormone enables the receptors to bind with high affinity to specific response elements in the promoters of target genes, resulting in stimulation or repression of transcription. While protein-protein interactions were early postulated to play an important role in the mechanism through which steroid hormone receptors exert their effects on transcription initiation, recent research has revealed a number of potential targets within the basal transcription machinery. Moreover, aided by the development of protein-protein interaction screening techniques, a rapidly increasing number of factors has been identified which associate with hormonally activated receptors and may be involved in the transactivation process. This review summarizes the basal transcription factors and cofactors which are targeted by steroid hormone receptors, describes their structure and properties, and discusses possible mechanisms.

Activation of transcription by progesterone receptor involves derepression of activation functions by a cofactor.

Hormone-induced progesterone receptors (PR) bound to response elements stimulate transcription initiation at target promoters through a mechanism that presumably involves cofactors or coactivators. To allow identification of such cofactors of transcriptional activation in a functional assay, we have established a reconstituted transcription system that is characterized by a specific loss of responsiveness to purified baculovirus-expressed wild type PR. In contrast to wild type PR, a C-terminally truncated PR mutant displayed strong activation potential in this system. As the purified recombinant full-length PR is capable of DNA binding, our results suggest that C-terminal sequences of PR mediate a cis-repression of N-terminal activation functions. Moreover, using this PR-nonresponsive transcription system, we identified and partially purified an activity from rat liver, termed COPRA (cofactor of PR activation), that restores transactivation by full-length PR. Characterization of COPRA revealed that this cofactor exhibits activator specificity and is not involved in basal transcription. We postulate that COPRA acts by relieving the repression of activation functions mediated by C-terminal sequences.

[Clinical and chemical laboratory course of HELLP syndrome--a retrospective analysis]. / Klinischer und laborchemischer Verlauf des HELLP-Syndroms--eine retrospektive Analyse.

The HELLP-Syndrom (hemolysis, elevated liver enzymes, low platelet count) is considered as a severe complication of eclampsia with unpredictable development of pregnancy including high maternal and fetal risk. The result of retrospective analysis of all deliveries of the years 1986-1991 at the UFK Marburg were 28 cases of proved HELLP-Syndrom. Medical history, correlation of clinical and laboratory findings as well as the development of the disease and the neonatal dates were evaluated by computerized documentation. The incidence of HELLP-Syndrom was 28 of 8111 deliveries at all (0,34%). 82% of the women with HELLP-Syndrom were primiparae. The leading symptom was right upper abdominal pain in 75%, which lasted already 5,7 days before presentation in the clinic. Hypertonus, edema and proteinuria were present in 71%, 61% and 89% of the cases. The diagnosis indicating laboratory finding was the thrombocytopenia (mean 62 G/l). In comparison to the thrombocytes, which were at the 4.-7. day pp in 89% within the normal range, the liver function tests normalized just between the 9. and 13. day pp (SGOT 89%, SGPT 77%). The shortening of the prepartal hospitalization from 6 days in 1986/87 to 8 hours in 1990/91 decreases the periand postnatal complication rate from 43% to 23%. 26/28 patients (92%) were delivered by caesarean section from healthy babies through which were 75% premature infants and in 27% of the cases small for gestational age additionally. We conclude that the decrease of the diagnosis-delivery interval and the intensive medical care are responsible for the diminution of the maternal and neonatal mortality rate to 0%.

Efficient synthesis of a 72-kDa mitochondrial polypeptide using the yeast Ty expression system.

Using the Ty system from yeast we report the efficient expression of a heterologous eukaryotic gene encoding a 72 kDa mitochondrial polypeptide. The pFM2IIBgIII expression vector was initially modified for this purpose by inserting the factor X(a) protease cleavage site. The TyA gene, which encodes the structural component of the yeast virus-like particles (VLPs), and the eukaryotic yst1 gene, encoding a 72 kDa mitochondrial tyrosyl-tRNA synthetase from the filamentous fungus Podospora anserina, were subsequently fused to the factor X(a) cleavage site. The resulting chimeric gene, in which the two polypeptide coding sequences are separated by the factor X(a) cleavage site, was expressed in yeast. High yield expression of this foreign protein, which was isolated from yeast transformants as hybrid TyVLPs, was verified after factor X(a) treatment by SDS polyacrylamide gel electrophoresis and antibody detection. The strategy presented here should be useful for expressing a wide variety of eukaryotic genes.

Identification of a transactivation function in the progesterone receptor that interacts with the TAFII110 subunit of the TFIID complex.

Transcriptional activation of target genes by the human progesterone receptor is thought to involve direct or indirect protein-protein interactions between the progesterone receptor and general transcription factors. A key role in transcription plays the general factors. A key role in transcription plays the general transcription factor TFIID, a multiprotein complex consisting of the TATA-binding protein and several tightly associated factors (TAFs). TAFs have been shown to be required for activated transcription and are, thus, potential targets of activator proteins. Using in vitro interaction assays, we could identify specific interactions between the progesterone receptor and the TATA-binding protein-associated factor dTAFII110. The dTAFII110 domain responsible for the interaction is distinct from that reported to suffice for binding to Sp1. Somewhat surprisingly, deletion analysis indicated that the previously identified activation functions 1 and 2 of the progesterone receptor are not required for this interaction but pointed to an important role of the DNA binding domain. In cotransfection experiments and an in vitro transcription assay, the DNA binding domain of the progesterone receptor displayed significant activation potential. These findings, taken together, suggest that an interaction between the progesterone receptor and TAFII110 may represent an important step in the mechanism of activation.

[Anesthesia with propofol during an exacerbated course of acute intermittent porphyria]. / Anästhesie mit Propofol bei einem exazerbierten Verlauf der akuten intermittierenden Porphyrie.

In the eighth week of pregnancy the medical indication for induced abortion was established due to an exacerbating acute intermittent porphyria with life-threatening neurological symptoms. delta-aminolaevulinic acid and porphobilinogen were excessively increased in urine prior to the operation. Anaesthesia was induced with a bolus of propofol, alfentanil and droperidol, maintained by 67% of nitrous oxide and small bolus injections of the three drugs. The patient regained consciousness immediately after the operation, and reached full orientation and cooperativeness within five minutes. The postoperative period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. Chorion gonadotropins and porphyria markers decreased within the next four weeks accompanied by a simultaneously progressing clinical improvement. The use of propofol and the other drugs appears justified even in exacerbated porphyria.