Mother-to-infant transmission of TT virus: prevalence, extent and mechanism of vertical transmission.

OBJECTIVE: It is currently unknown which mechanisms are responsible for TT virus (TTV) infection in early childhood and whether it may be transmitted in utero from mother to infant. METHODS: The prevalence, mode and extent of maternal TTV transmission was investigated by testing blood, cord blood and breast milk samples from mother-infant pairs for the existence of the novel DNA virus. RESULTS: By means of polymerase chain reaction, TTV DNA was detected in 57 (41.3%) of 138 mothers and in 19 (13.8%) of 138 cord blood samples; therefore 33.3% of infants are likely to be infected by their mothers during the fetal period. Direct sequencing of TTV DNA from 2 mother-child pairs showed identical isolates. Follow-up sera from 3 TTV infected babies showed persistence of viremia. In blood samples from newborns older than 1 week 9 (27.3%) of 33 sera were TTV-positive. Viral sequences were also detected in 2 of 2 breast milk samples. In none of the infected subjects were biochemical or clinical signs of hepatitis observed. CONCLUSIONS: Our data prove that TT virus is efficiently transmitted transplacentally. The increase of its prevalence in the group of newborns older than 1 week suggests that it may be furthermore transmitted postnatally. Therefore in our Caucasian population, vertical transmission, particularly in utero transmission, of TTV is likely to account for a major part of TTV infection in early childhood. However, no disease activity could be established for the novel virus by this infection route.

The effects of long-term nicotine treatment on locomotion, exploration and memory in young and old rats.

To assess the effects of long-term treatment with nicotine on several behavioral measures (locomotor activity, exploratory efficiency, habituation, short-term and long-term memory) of young (5 months) and old (22 months) rats in a hexagonal tunnel maze, nicotine was added to the drinking water (0, 20 or 50 mg/l) for up to 131 experimental days. With the exception of effects on exploratory efficiency, young and old rats did not differ in their response to the drug. Nicotine decreased body weight throughout the experiment. Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water. Nicotine increased locomotor activity throughout the experiment. When nicotine treatment was discontinued during a 7-day withdrawal period, locomotor activity immediately dropped to control values. Intertrial habituation was not affected by nicotine. Long-term nicotine treatment had an attenuating effect on exploratory efficiency in young rats; however, the drug did not influence performance in tasks measuring spatial memory. Finally, age increased weight, decreased locomotor activity and impaired exploratory efficiency and short-term memory. Age, however, did not affect the performance of the long-term memory task.

Effects of chlordiazepoxide and imipramine on maze patrolling within two different maze configurations by psychogenetically selected lines of rats.

Male rats of two lines of rats psychogenetically selected and bred for extremes in performance in shuttle box avoidance received an acute IP injection of chlordiazepoxide (CDP; 2.5, 5.0, 10.0 mg/kg), imipramine HCl (IMI: 0.33, 1.0, or 3.0 mg/kg), or vehicle. The rats were placed, 35 min after injection, in an enclosed maze with either a simple configuration with an unilluminated central arena or a complex configuration with a brightly illuminated central arena, and spontaneous maze patrolling was evaluated. Total locomotor activity during the 6-min maze test was significantly reduced by 5--10 mg/kg CDP for both RHA/Verh and RLA/Verh lines of rats in both the simple and the complex maze configurations. Treatment with 10 mg/kg CDP reduced the total explored area for both rat lines in both maze configurations. In addition, the maze area explored by RHA/Verh rats was also reduced by 5.0 mg/kg CDP for the simple configuration and by 2.5 and 5.0 mg/kg CDP for the complex configuration. Entry into the unilluminated central field of the simple maze was reduced by 5--10 mg/kg CDP only in RHA/Verh rats. In contrast, 2.5 mg/kg CDP significantly increased entry into the brightly illuminated central arena of the complex maze for the RLA/Verh rats. The doses of IMI used were without effect on the parameters of maze patrolling behavior evaluated, with the single exception that the locomotor activity of RHA/Verh rats tested in the simple maze configuration was decreased by 3.0 mg/kg IMI. The results indicate that, although the effects of CDP were generally similar for total activity and the area explored in the two psychogenetic lines investigated, there was a qualitative difference in its effect on entry into an illuminated arena.

Behavioral effects of experimental portacaval anastomosis measured in Dashiell and radial tunnel maze configurations.

Male rats which had received either a surgically constructed end-to-side portacaval shunt or sham surgery were maintained on a normal diet of laboratory chow or on chow plus a low tryptophan, low protein supplement. In 6-min long daily tests carried out in both a Dashiell and a radial tunnel maze configuration for 6-day blocks, numerous behavioral parameters were automatically registered via a computer-interfaced maze system. The dietary condition failed to affect the activity level of the two surgical groups. After collapsing the behavioral data across dietary condition, discriminant analysis yielded two significant factors which were subsequently found to differentiate the two surgical groups: the intrasession habituation of locomotion and the total activity within a session. The rate of intrasession activity decline was significantly more rapid for portacaval-shunted rats than their surgical controls, but only in the Dashiell configuration. The control rats exhibited significantly greater total activity during evaluation in the radial maze; whereas in the Dashiell configuration the total activity of the portacaval-shunted rats was higher than controls only during the first few days but lower during the final few days of testing. These results indicate that, depending upon the maze configuration, spontaneous locomotor activity and the decline of activity within a test session were altered in the rat with portal-systemic shunting of the circulation, which has been proposed as an animal model of chronic liver dysfunction.

Reduction of nicotine-induced hyperactivity by pCPA.

Spontaneous locomotion of female Wistar rats was measured in six to ten minute sessions in an automated tunnel maze consisting of a central arena and six radially symmetrical angled arms. Nicotine (0.2 mg/kg subcutaneous, 20-30 minutes pretest) increased total arm visit frequency, but intrasession habituation and number of repetitive arm visits in the first six choices were not affected. pCPA (300 mg/kg IP three days pretest) reduced arm-visit frequency in nicotine-, but not in saline-treated rats; it had no effect on intrasession habituation or number of repetitions in either treatment group. 5-HTP (50 mg/kg IP 90 minutes pretest) reduced arm entry frequency in saline-, nicotine-, and pCPA-treated groups. Possible reasons for this discrepancy are discussed.

Effects of tunnel maze complexity on caffeinic hyperactivity in the rat.

The study investigated effects of caffeine on spontaneous tunnel locomotion without consummatory reward. The stimulant effects consisted in delayed intrasession habituation, and they differed in magnitude according to dosage and the complexity of the tunnel arrangements. In a simple hexagonal tunnel without choice points, 16 mg/kg BW produced greater stimulation than other doses, and this most efficient dose became less effective if tunnels were arranged according to the radial maze paradigm. No stimulation was obtained if an open field was incorporated into the maze. Caffeine also had no effect on open field behavior, but it tended to improve the efficiency of radial arm maze patrolling, and its significantly depressed exploration of short tunnel arms branching from the radial arms in favor of exploration of the more distant radial tunnel ends.

In vitro study of human alveolar macrophages inflammatory mediator transcriptions and releases induced by soot FR 101, Printex 90, titandioxide and Chrysotile B.

Soot FR 101, Printex 90 and Chrysotile B are frequently found in indoor air pollutants phagocytized by alveolar macrophages (AM) involved in inflammatory pulmonary processes as, e.g. in cytokine secretions. The transcription factor NF-kappaB has a role in the trans-duction pathway of proinflammatory cytokines like IL-1beta, IL-6 and TNF-alpha. We therefore investigated whether the transcription factor NF-kappaB and subsequent inflammatory cytokine secretions by AM are induced by exposure to these particles compared to the inert TiO2. AM were incubated for 90 min at particle concentrations of up to 100 microg/10(6) cells. Sequential reverse transcription and semiquantitative cDNA amplification (RT-PCR) was used to measure NF-kappaB and cytokine mRNA expressions. Compared to control exposures these particles induced an up to 4.6-fold increase in gene expression of the transcription factor NF-kappaB (p < 0.01), resulting in up to 12.9-fold enhanced transcription rates of IL-1beta, IL-6 and TNF-alpha (p <0.05). The particles and fibre dependent increases in mRNA reached maximum levels at 90 min post exposure. After an exposure time of 8 hrs, IL-1beta, IL-6 and TNF-alpha proteins, measured by enzyme-linked immunosorbent assays (ELISA), were significant elevated in supernatants of AM, revealing an up to 30.5-fold increase in TNF-alpha secretion rates (p <0.01). Our results suggest that exposure of human AM to soot FR 101, Printex 90, TiO2 and Chrysotile B induce the transcription and production of proinflammatory cytokines via NF-kappaB and may play an important role in the pathogenesis of airway disease and lung parenchymal injury.

Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis.

OBJECTIVE: Evaluation of systematic epidemiological data regarding clinical characteristics, sex distribution and autoantibody pattern in Caucasian children with autoimmune hepatitis (AIH). STUDY DESIGN: Data of 142 children presenting with AIH (97 girls and 45 boys) have been analysed for their clinical, serological, and histological profile. RESULTS: Clinical findings were jaundice (58%), unspecific weakness (57%), anorexia (47%), abdominal pain (38%) and paleness (26%). One hundred and three children (73%) (68 girls, 35 boys, 1.9:1) had AIH type 1 and 35 patients (25%) (27 girls, 8 boys, 3.4:1) type 2 due to specific autoantibodies. Four children could not be classified. Histology of 122 children revealed active hepatitis in 64 (52%), cirrhosis in 46 (38%), and mild inflammatory activity in 12 individuals (10%). The most prevalent HLA type was B8. CONCLUSION: In our cohort the prevalence of AIH was half as frequent in boys as in girls. Type 1 was the most frequent diagnosis (73%) and was more prevalent in older children. Type 2 was equally age distributed. The clinical presentation of AIH in children was unspecific and type I and type II could only be differentiated by the determination of the specific autoantibodies. Ninety percent of patients presented with high inflammatory activity or liver cirrhosis.

Age-related changes in working and reference memory performance and locomotor activity in the Wistar rat.

Wistar rats of three age groups were tested in an automated tunnel-maze system of variable geometry to investigate whether changes in spontaneous locomotor activity and in learning and memory develop differentially or in a correlated fashion as a function of age. Senescent (30 months) as well as mature-adult (17 months) rats showed an age-correlated decline of locomotor activity as compared to the mature-young (5 months) group. Both working-memory (measured as within-trial arm discrimination performance) and reference-memory (measured as avoidance of "blind alley" visits) were severely affected in the senescent group, whereas the middle-aged animals suffered only from a working-memory deficit. The findings provide evidence that locomotor deficits do not necessarily interfere in the assessment of age-related changes in cognitive performance. Furthermore the results support the hypothesis that working and reference memory have different underlying physiological correlates and that these neuronal systems are differentially affected by the aging process.

Automated recording of rat activity in a 6-arm radial maze for routine evaluation of behaviour in subchronic toxicity studies.

Using the 6-arm radial maze constructed by Bättig et al. and FitzGerald at el., the spatial locomotor activity of rats can be characterized during five-minute-sessions. Due to the complexity of the maze the rats keep patrolling the gangways without being rewarded for it. The optimal behaviour is reached by visiting all six arms successively until a visit is repeated. Hippocampal lesioned rats, with the according behavioural disturbances, show more reenterings than the control animals. Each arm of the maze is provided with a short blind alley and a long main gangway. After several trials, blind alley entries reach a low and stable level: the rat enters the main arm rather than the blind alley. The decision of entering the main alley depends on the "reference memory", of entering the alleys in the proper sequence, depends on the "working memory". Thus, correlates of long- and short-term memory can be studied. Rats learn to achieve the proper maze behaviour during five successive daily sessions each of a five minute term. By then they have reached a stable behaviour. The monitoring by photobeams of the rat-behaviour is reconstructed by a microprocessor and automatically evaluated.

[Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases]. / Pyostomatitis vegetans und Morbus Crohn. Eine spezifische Assoziation zweier Krankheiten.

HISTORY AND CLINICAL FINDINGS: A 27-year-old man was referred to the dermatological out-patient clinic because of inflammatory changes in the oral mucosa of unknown cause. 5 months earlier he had been diagnosed as having Crohn's disease of the terminal ileum. On both sides of the buccal mucosa there were rough erythematous vegetations and disseminated miliary abscesses, which extended to the labial gingiva and the soft palate. Further physical examination was unremarkable. INVESTIGATIONS: Several inflammatory parameters were increased: C-reactive protein 100 mg/l, erythrocyte sedimentation rate 55/88 mm, eosinophilic cationic protein 35.8 ng/ml (normal range 2.3-16 ng/ml). White cell count was normal (7,25/nl), with a lymphocytopenia of 11.9%. There was no eosinophilia. Haemoglobin was reduced to 11.6 g/dl and the platelets raised to 526/nl. Smears of the oral mucosa showed no fungal, viral or bacterial infection. Biopsy revealed leucocytic microabscesses in the epithelium, granulation tissue and flat ulcerations with adjoining superficial necrotic zones. DIAGNOSIS, TREATMENT AND COURSE: The clinical and histological picture as well as the association with Crohn's disease (CD) suggested pyostomatitis vegetans (PV). The PV was treated with disinfectant mouth washes which improved the subjective findings. Budesonide was given for CD. CONCLUSION: PV is a rare and usually isolated condition, but it can also occur in association with a chronic gastrointestinal disease such as ulcerative colitis and Crohn's disease. The diagnosis of PV indicates a thorough gastroenterological investigation.

The hepatitis B virus seroconversion to anti-HBe is frequently associated with HBV genotype changes and selection of preS2-defective particles in chronically infected children.

In order to investigate the generation and selection of hepatitis B virus mutants and the influence of interferon on their evolution, a longitudinal study including 22 patients was performed. The complete preS1/S2 open reading frame was analyzed by direct sequencing from serum samples obtained before and after seroconversion to anti-HBe in 11 children without alpha-interferon treatment. Furthermore, in 11 cases with therapy additional samples obtained during interferon therapy were investigated. The comparison of each patient's preS sequences analyzed before and during therapy did not show any nucleotide change, while in both groups numerous silent and missense mutations were found immediately after seroconversion. Surprisingly, in 7 cases the hepatitis B virus changed genotype from A to D (subtype adw to ayw) after seroconversion. Additional rearrangements were observed in 4 patients. In 3 cases the selection of preS2 start codon mutants was detected after seroconversion and in 1 individual a 183-nucleotide deletion was found during and after HBeAg positivity. In conclusion, the emergence of preS rearrangements and numerous base exchanges provide evidence for a strong selection process focused against the preS region. Moreover, the appearance of genotype changes after anti-HBe seroconversion reveales a thus far unrecognized event during the natural course of HBV infection in childhood.

Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA.

Alveolar macrophages (AM) play a decisive role in the immunologic defense system of the lung and in inflammatory pulmonary pathomechanisms. AM and blood monocytes (BM) were exposed to chrysotile B, soot FR 101, and Printex 90 (P 90). We evaluated the reactive oxygen intermediate (ROI) release of AM and BM after particle exposure. ROI release was measured by chemiluminescence. Thirty-minute exposure caused a significant (up to 2.5-fold) increase in ROI release of AM (100 micrograms/10(6) cells) compared with control experiments (p < 0.01). Identical exposure conditions for BM resulted in a similar reaction pattern (maximum 2.2-fold increase in ROI release; p < 0.05). After a 90-min particle exposure at concentrations of 10 and 100 micrograms/10(6) cells, we investigated the steady-state level of p50/p105 mRNA encoding for the precursor protein of the p50 subunit of nuclear factor kappa B (NF-kappa B) by semiquantitative reverse transcription-polymerase chain reaction. One hundred micrograms Chrysotile B, FR 101, or P 90 induced a significant maximum 4.0-fold up-regulation of NF-kappa B gene expression in AM and a 3.3-fold up-regulation in BM (p < 0.05). The addition of superoxide dismutase (200 U/ml) to particle- and fiber-exposed macrophages resulted in inhibition of ROI release and a decrease in NF-kappa B mRNA expression (70%). NF-kappa B is an important transcription factor involved in the regulation of numerous genes (e.g., for inflammatory cytokines, and cytokine receptors). These cytokines are supposed to be involved in inflammatory pathomechanisms in bronchial epithelial cells, which result, for example, in chronic obstructive pulmonary disease. Our results suggest that particle-induced ROI release is associated with an increase in NF-kappa B (p50/p105) mRNA steady-state level.