Lilliputian and negative hallucinations in a patient with probable encephalomyelitis disseminata.

A patient who showed Lilliputian hallucinations and negative hallucinations in the course of probable disseminated encephalomyelitis is described. At the age of 14 years the patient experienced a transient, flaccid paresis of the right leg. Eighteen years later she suddenly developed paranoid-hallucinatory symptoms accompanied by atypical visual hallucinations. She did not recover completely and until now she has suffered at least once every year from an episode with psychotic symptoms. During the most recent of these episodes, MRI revealed several disseminated supra- and infratentorial foci in the brain. Two of them, in the left cerebral peduncle and in the left occipital white matter are discussed as the cause of her visual hallucinatory symptoms.

[Expanded nuclear magnetic resonance studies in Borna disease virus seropositive psychiatric patients and control probands]. / Erweiterte kernspintomographische Untersuchungen bei Borna-disease-Virus -seropositiven psychiatrischen Patienten und Kontrollen.

There is growing evidence, that Borna Disease virus (BDV) or a variant may cause neuropsychiatric disorders in humans. The presence of specific BDV serum antibodies indicates an earlier contact with BDV. Earlier MRI results showing a raised prevalence of white matter lesions in BDV-seropositive psychiatric patients, possibly indicating encephalitic lesions, are not confirmed in this extended study, however in BDV-seropositive psychiatric patients the occurrence of cerebral atrophy seems to be more frequent, a finding compatible with hydrocephalus e vacuo found in animals after BDV-encephalitis. Because encephalitic lesions in BD are predominantly found in the gray matter of the brain, which is hardly visualized by MRI, the failure to detect lesions in BDV-seropositive patients could be due to methodological problems.

Regulation of tumor necrosis factor-alpha-mRNA synthesis and distribution of tumor necrosis factor-alpha-mRNA synthesizing cells in rat liver during experimental endotoxemia.

Stimulated liver macrophages (Kupffer cells) are known to release a variety of inflammation-related substances, e.g. cytokines, prostanoids, and reactive oxygen intermediates. For instance, exposure of Kupffer cells in vitro to lipopolysaccharide (endotoxin) leads to a strongly enhanced synthesis of the mRNA for tumor necrosis factor-alpha, the release of the mature protein into culture media. These events are influenced by prostanoids and corticoid hormones. Kupffer cells are thought to be the only source of tumor necrosis factor-alpha within the hepatic sinusoid, but neither this cell specificity nor the regulatory influence of glucocorticoids or prostanoids has been confirmed in the intact organ. Using non-radioactive in situ hybridization, it was possible to obtain specific signals for tumor necrosis factor-alpha-mRNA in individual Kupffer cells uniformly distributed (as compared to Kupffer cells detected by immunohistochemistry) throughout the liver. Kupffer cells were the only cells in the hepatic sinusoids of lipopolysaccharide-perfused livers to express mRNA for tumor necrosis factor-alpha. Simultaneous addition of endotoxin plus dexamethasone and endotoxin and prostaglandin E2 completely suppressed the synthesis of this mRNA. Unexpectedly, the presence of mRNA for tumor necrosis factor-alpha was also detected in the intrahepatic bile duct epithelium of lipopolysaccharide-perfused livers. It is known that biologically active endotoxin is secreted via the bile ducts. These results seem to indicate that bile duct epithelium responds to inflammatory agents with synthesis of tumor necrosis factor-alpha-mRNA. One must also consider new functional aspects of bile duct epithelium in chronic inflammatory diseases, e.g. primary biliary cirrhosis, chronic sclerosing cholangitis or graft-versus-host disease.

Isolation of a cDNA encoding the human brain serotonin transporter.

A cDNA encoding a serotonin transporter (5-HTT) in the human dorsal raphe nucleus was isolated and sequenced using cross-species amplification of human 5-HTT partial cDNA by the polymerase chain reaction (PCR) and the RACE-PCR procedure, designed for rapid amplification of 3' and 5' cDNA ends. The cDNA contains an open reading frame encoding a hydrophobic polypeptide of 630 amino acids with a calculated molecular weight of approximately 70 kDa. The human 5-HTT is approximately 92% homologous to the rat protein but contains an additional consensus phosphorylation site for cAMP-dependent protein kinase recognition located in the cytoplasmic N-terminal region, while a potential protein kinase C phosphorylation site identified in the rat homolog is not conserved in the human 5-HTT. Hydropathicity analysis revealed twelve membrane spanning segments, a topology proposed for other cloned sodium-dependent transporters.

Rat tumor necrosis factor-alpha. Transcription in rat Kupffer cells and in vitro posttranslational processing based on a PCR-derived cDNA.

A DNA fragment with a reading frame of 708 basepairs coding for TNF-alpha from rat liver was cloned by the polymerase chain reaction. Using this species-specific cDNA a biotin-labelled antisense (-)RNA was transcribed. This probe was used for Northern blot analysis of TNF-alpha gene activation. Exposure of rat Kupffer cells to LPS led to a time-dependent change of TNF-alpha-mRNA expression with a maximum between one and two hours after stimulation. In vitro translation was carried out with sense (+)RNA in the presence of microsomes. SDS gel electrophoresis of the immunoprecipitated proteins revealed the formation of polypeptides with estimated molar masses of 26 and 17 kDa. They correspond to the estimated molar masses of a precursor of TNF-alpha encoded by the entire reading frame and of the mature form of TNF-alpha, respectively. A sequence of the cDNA assumed to code for the leader peptide was deleted and the remainder used for the construction of an expression plasmid. Using this construct, biologically active mature TNF-alpha was expressed in E. coli (10(6) units TNF-alpha per liter of culture medium). The propeptide as well as the biologically active TNF-alpha possess a homology of 92 and 76% to mouse and human TNF-alpha, respectively.

Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase.

Tumor necrosis factor (TNF) has been shown to mediate lipopolysaccharide-induced neutrophil adhesion to liver sinusoidal endothelium in vivo. Female NMRI mice received either 5 micrograms lipopolysaccharide (R595) per animal alone (model A) or together with 116 mumol D-galactosamine (model B). One hour after injection, TNF activity in the serum was detectable to an equal extent in both models. Neutrophils in the liver, which had been identified by chloroacetate esterase staining of liver sections and quantitated by light microscopy, started to increase at 1 h and were elevated 10-fold above baseline at 6 h after application in (A) and (B). If 0.5 micrograms TNF instead of lipopolysaccharide was injected alone (model C) or together with D-galactosamine (model D), neutrophil influx into the liver was comparable to that observed in (A) or (B). Alanine aminotransferase activity in the serum was nearly normal in (A) and (C) 6 h after injection, while it reached levels up to 50-fold above baseline in models (B) and (D). This reflects the well-known D-galactosamine sensitization against lipopolysaccharide or TNF. Furthermore, degranulation of a large number of intrasinusoidal neutrophils could be observed 9 h after lipopolysaccharide-galactosamine injection. The administration of 116 mumol D-galactosamine per animal alone led neither to a measurable TNF activity in the serum nor to an increase in alanine aminotransferase activity or number of liver neutrophils. If the animals had received 50 microliter turpentine subcutaneously 24 h prior to lipopolysaccharide, TNF or D-galactosamine injection, the induced acute-phase reaction suppressed the increase of liver neutrophils in all models. Acute-phase reaction also prevented neutrophil degranulation and the rise of alanine aminotransferase in (B) to a great extent, while serum TNF activity was only minimally affected. It is concluded that TNF mediates neutrophil adhesion to the sinusoidal endothelium in vivo and that acute-phase reactants prevent lipopolysaccharide- or TNF-induced neutrophil influx into the liver.