Quasi-continuous-time impurity solver for the dynamical mean-field theory with linear scaling in the inverse temperature.

We present an algorithm for solving the self-consistency equations of the dynamical mean-field theory (DMFT) with high precision and efficiency at low temperatures. In each DMFT iteration, the impurity problem is mapped to an auxiliary Hamiltonian, for which the Green function is computed by combining determinantal quantum Monte Carlo (BSS-QMC) calculations with a multigrid extrapolation procedure. The method is numerically exact, i.e., yields results which are free of significant Trotter errors, but retains the BSS advantage, compared to direct QMC impurity solvers, of linear (instead of cubic) scaling with the inverse temperature. The new algorithm is applied to the half-filled Hubbard model close to the Mott transition; detailed comparisons with exact diagonalization, Hirsch-Fye QMC, and continuous-time QMC are provided.

Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas.

BACKGROUND: Cholangiocellular carcinomas and gallbladder carcinomas are highly aggressive tumours with a poor prognosis and are generally regarded as chemoresistant tumours. Overexpression of ATP-binding cassette transporters of the multidrug resistance protein (MDR) and multidrug resistance-related protein (MRP) family in cancer cells is a major cause for the multidrug resistance phenotype in vitro and in vivo. To further define the role of MRP family members in biliary tract cancer, we studied the expression and localization of MRP2 and MRP3 in cholangiocellular carcinomas and gallbladder carcinomas. MATERIALS AND METHODS: The expression and cellular localization of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas and gallbladder carcinomas were analysed by immunohistochemistry using isoform-specific antibodies. Expression of MRP isoforms was studied in vitro in Mz-ChA-1 cells derived from gallbladder adenocarcinoma by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and immunofluorescence microscopy. RESULTS: Mz-ChA-1 cells constitutively expressed MDR P-glycoproteins, MRP1, MRP2 and MRP3 by RT-PCR, immunoblotting and immunofluorescence microscopy. MRP2 and MRP3 are expressed in the respective apical and basolateral membrane domains. MRP3 was the predominant MRP isoform in gallbladder carcinomas (93%) and cholangiocellular carcinomas (57%), whereas MRP2 expression was detected in only 29% of gallbladder carcinomas and was undetectable in cholangiocellular carcinomas. CONCLUSIONS: Our findings suggest that the intrinsic multidrug resistance of cholangiocellular and gallbladder carcinomas seems to be independent of MRP2 expression while the expression of MRP3 may contribute to the MDR phenotype.

[Influence of prism overcorrection on residual postoperative strabismus]. / Einfluss der Prismenüberkorrektur auf den postoperativen Restschielwinkel.

BACKGROUND: Prism overcorrection is a complementary procedure to reduce the residual postoperative esotropia caused by anomalous retinal correspondence (ARC) after surgery for esotropia. We have investigated the results of this treatment. PATIENTS AND METHODS: For Group 1, the files of 63 patients treated with postoperative prism overcorrection in the Department of Ophthalmology, University of Giessen, were evaluated regarding the pre-and postoperative squint angles (SPCT, simultaneous and APCT, alternate prism and cover test) and the angle of ARC, determined by the red filter test and by the increase of esotropia after neutralisation of the squint angle (APCT). Postoperatively, squint angles had been measured immediately (APCT) after removal of the eye patch and 10 minutes to 2 hours later (SPCT and APCT). Subsequently, prism overcorrection was performed with a Fresnel prism foil (40 PD basis temporally) in front of the fellow eye for a maximum of 3 months. After 3 months, SPCT and APCT were performed. For Group 2, the files of 28 patients with a preoperative angle of ARC of 5 degrees or more, treated in the Department of Ophthalmology, University of Heidelberg, were evaluated. These patients had not been treated with prism overcorrection. The squint angles had been measured (SPCT and APCT) on the preoperative day, on the first postoperative day, a few hours after removing the eye patch, and after three months. RESULTS: For Group 1, at surgery, the patients were 4 to 12 years old (median: 6.2 years). The preoperative squint angle ranged from + 5 degrees to + 27 degrees (median: + 12 degrees) in the SPCT and from + 7 degrees to + 27 degrees (median: + 14 degrees) in the APCT. The angle of ARC was between + 4 degrees and + 15 degrees (median: + 7 degrees). Both combined recess and resect surgery (with or without additional oblique muscle surgery) or bilateral retroequatorial medial rectus myopexy, in part depending on the squint angle pattern with medial rectus recession, were performed. Immediately after removing the patch, the squint angle (APCT) was between - 10 degrees and + 5 degrees (median: + 1 degrees). Ten minutes to 2 hours later, the manifest squint angle ranged from 0 to + 12 degrees (median: + 7 degrees). The angle had decreased significantly to - 6 to + 12 degrees (median: + 5 degrees) after 3 months. For Group 2, the patients' ages were between 5 and 12 years (median: 6.5 years). The squint angles ranged from + 11.5 degrees to + 35 degrees (median: + 20 degrees) in the SPCT and APCT. The angle of ARC was between + 5 degrees and + 17 degrees (median: + 8 degrees). Combined recess and resect surgery or bilateral recession of the medial rectus (with or without oblique muscle surgery both) were performed. The SPCT several hours after removal of the patch showed angles of - 4 degrees to + 14 degrees (median: + 4.25 degrees). Three months later the manifest squint angles ranged from - 5 degrees to + 14 degrees (median: + 3 degrees). DISCUSSION: After prism overcorrection (Group 1), there was a significant reduction of the residual esotropia. Without this additional treatment (Group 2), there was no significant change in the postoperative squint angle. However, neither the positive outcome in Group 1 nor the difference to Group 2 do unequivocally prove that there is a beneficial effect of prism overcorrection, since preoperative conditions were different and the sample size in Group 2 was small, especially after matching for equal preoperative conditions. A spontaneous reduction of the postoperative esotropia cannot be excluded. Further studies are necessary in order to investigate the specific effect of prism overcorrection.

Oral anticoagulation in atrial fibrillation: A pan-European patient survey.

BACKGROUND: Anticoagulation with vitamin K antagonists (VKAs) provides effective stroke prophylaxis in patients with atrial fibrillation (AF). Optimisation of such therapy requires frequent monitoring, dose adjustments and stringent lifestyle restrictions. We conducted a large multinational survey in patients with chronic AF to gain insights into their perceptions and understanding of VKA use. METHODS: Eligible patients were adults with AF who had been prescribed VKAs for at least 1 year. A total of 711 patient interviews were conducted in seven European countries during June and July 2004. RESULTS: The majority of patients (58% male; mean age 68 years) claimed to understand their treatment programme; despite this, only 7% knew that VKA use is aimed at preventing strokes and 24% stated that they would have liked more information. Patients attended an average of 14 monitoring sessions in the previous year; however, 21% missed appointments, especially younger patients (<65 years). The International Normalized Ratio (INR) was within the target range in most or all of the last five to ten visits in 64% of patients; nonetheless, 38% were not aware that an INR outside the target range is associated with health risks. On average, patients required dose adjustments every four sessions. VKA treatment impacted 67% of patients in terms of diet, socialising, career and independence, especially younger patients (74%). CONCLUSIONS: Monitoring, dose adjustments and lifestyle restrictions to optimise the intensity of anticoagulation with VKAs are problematic for patients with AF, and their knowledge of the consequences of such therapy is often poor.

Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic acid in primary sclerosing cholangitis.

In primary sclerosing cholangitis (PSC), biliary enrichment of ursodeoxycholic acid (UDCA) may represent the decisive factor for its presumable beneficial effect. Up to now it is not clear how colitis and colectomy with ileo-anal pouch affect the biliary enrichment of UDCA and the biliary bile acid composition. We determined the biliary bile acid composition in 63 patients with PSC including 7 patients with ileo-anal pouch, 31 patients with colitis, and 25 patients without colitis. No differences existed between patients with and those without colitis. In patients with colectomy and pouch at a UDCA dose of 17.7 +/- 1.6 mg/kg (n = 7), biliary UDCA represented 46.4 +/- 6.7% (mean +/- SD) of total bile acids. An increase in the dose in six pouch patients from 12.5 +/- 0.9 to 22.3 +/- 1.6 mg/kg led to a slight increase in biliary enrichment of UDCA, from 39.8 +/- 8.1 to 49.4 +/- 10.7%. In five of seven patients with ileo-anal pouch, biliary UDCA enrichment was within the normal range, and in two of seven it was permanently or intermittently abnormally low. During UDCA treatment, in pouch patients the biliary content of deoxycholic acid and lithocholic acid was reduced, whereas all other bile acids were unchanged. In a minority of patients with ileo-anal pouch, biliary enrichment of UDCA may be markedly reduced, whereas patients with colitis have a biliary UDCA enrichment not different from that of patient without colitis.

Gender-specific expression of liver organic anion transporters in rat.

BACKGROUND: Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. MATERIALS AND METHODS: Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. RESULTS: In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. CONCLUSIONS: In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.

The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney.

It is generally accepted that iron homeostasis is mainly controlled in the gastrointestinal tract by absorption of dietary iron. However, recent studies have shown that the kidneys are also involved in iron metabolism. Since the iron-regulatory and antimicrobial peptide hormone hepcidin was originally isolated from human urine we have investigated the expression as well as the zonal and cellular localization of hepcidin in the mammalian kidney and developed an ELISA assay to analyze hepcidin concentrations in serum and urine. The expression of hepcidin was shown by RT-PCR and immunoblot experiments; its cellular localization was studied by immunocytochemistry in human, mouse and rat kidney, which revealed similar patterns of immunoreactivity. Hepcidin expression was absent from the proximal tubule and descending and ascending thin limbs. There was strong expression in the thick ascending limb of the cortex and in connecting tubules. Moderate expression was noted in the thick ascending limb and collecting ducts of the medulla and in collecting ducts of the papilla. Importantly, the cells of the macula densa were unstained. At the cellular level, hepcidin was localized to the apical cell pole of the renal epithelial cells. Based on its presence in urine, hepcidin may be released apically into the urine. Enhanced levels of hepcidin were determined in patients with chronic renal insuffciency (156.8 ng/ml, controls 104.2 ng/ml) indicating that the kidneys may metabolize and/or eliminate the circulating peptide. From the expression of hepcidin in the mammalian kidney, we have concluded that the iron-regulatory hormone is an intrinsic renal peptide which is not only eliminated by the kidney but is also synthesized in the kidney tubular system. Localization of hepcidin in the kidney implicates an iron-regulatory role of this peptide hormone in the renal tubular system, possibly in connection with the iron transporter divalent metal transporter-1.

Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TGepsilon26 mice leading to the prevention of colitis.

BACKGROUND AND AIMS: Erroneous thymic selection of developing T lymphocytes may be responsible for the expansion of self reactive T cells or may contribute to the absence of regulatory T cells important in controlling peripheral inflammatory processes. Colitis in bone marrow (BM) transplanted Tgepsilon26 mice is induced by abnormally activated T cells developing in an aberrant thymic microenvironment. We investigated the protective role of regulatory CD4+CD25+ T cells in this model. METHODS: BM from (C57BL/6 x CBA/J) F1 mice was transplanted into specific pathogen free Tgepsilon26 mice (BM-->Tgepsilon26). Transplanted mice received no cells (control), sorted CD4+CD25+, or CD4+CD25- cells from mesenteric lymph nodes (MLN) of normal mice. MLN cell subsets were analysed using membrane markers. Cytokine secretion of MLN cells was measured using intracellular cytokine staining and cytokine secretion in anti-CD3 stimulated cell cultures. Colitis was measured by histological scores. RESULTS: CD4+CD25+ cells were reduced in the MLNs of BM-->Tgepsilon26 mice. Transfer of regulatory CD4CD4+CD25+ but not of CD4+CD25- cells reduced the number of MLN CD4+ T cells in BM-->Tgepsilon26 recipients and increased the number of MLN CD8+ cells, thereby normalising the CD4+/CD8+ ratio. CD4+CD25+ but not CD4+CD25- cell transfer into BM-->Tgepsilon26 mice reduced the number of tumour necrosis factor alpha+ CD4+ cells and increased the secretion of transforming growth factor beta by MLN cells. Transfer of 3 x 10(5) CD4+CD25+ cells after BM transplantation into Tgepsilon26 mice prevented colitis whereas CD4+CD25- cells had no protective effect. CONCLUSIONS: These results suggest that defective selection or induction of regulatory T cells in the abnormal thymus is responsible for the development of colitis in BM-->Tgepsilon26 mice. Transfer of CD4+CD25+ cells can control intestinal inflammation in BM-->Tgepsilon26 mice by normalising the number and function of the MLN T cell pool.

Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia.

BACKGROUND AND AIMS: The hepatic peptide hormone hepcidin, which has recently been isolated from human plasma and urine, is thought to be a central regulator of iron homeostasis. We investigated the presence and cellular localisation of hepcidin in the liver and developed a non-invasive assay to analyse its regulation in patients with hereditary haemochromatosis (HH), chronic renal insufficiency (CRI), and renal anaemia (RA). METHODS: Expression and localisation of hepcidin was shown by reverse transcription-polymerase chain reaction, western blot, immunocytochemistry, and immunofluorescence in human and guinea pig liver. Serum concentrations were determined in various groups of patients using a sensitive enzyme linked immunosorbent assay (ELISA). RESULTS: Western blot analysis with region specific antibodies identified a approximately 10 kDa peptide corresponding to the apparent molecular mass of pro-hepcidin. Localisation studies revealed that pro-hepcidin is expressed at the basolateral membrane domain of hepatocytes and is also present in blood. We developed a stable sensitive ELISA for detection and determination of pro-hepcidin in human serum. Mean pro-hepcidin level in human serum of healthy volunteers was 106.2 ng/ml. Enhanced levels of pro-hepcidin (148.1 ng/ml) were found in patients with CRI but normal haemoglobin values, indicating that the kidneys may metabolise and/or eliminate the circulating hormone. In contrast, concentrations of pro-hepcidin were significantly decreased in patients with HH (70.2 ng/ml) and also in patients with RA (115.0 ng/ml) compared with the CRI group. CONCLUSIONS: From the detection of pro-hepcidin in human serum, we conclude that the prohormone may be involved in the regulation of iron metabolism in HH. Decreased pro-hepcidin levels could play an important role in the pathogenesis of HH.

Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia.

BACKGROUND & AIMS: The multidrug resistance protein (MRP) isoforms MRP2 (ABCC2) and MRP3 (ABCC3) play a decisive role in the hepatic secretion of endogenous and xenobiotic conjugates and are differentially expressed in hepatocytes and cholangiocytes. The epithelium of the gallbladder considerably modifies the composition of primary hepatic bile by absorption and secretion; however, the underlying transport mechanisms were largely unknown. Localization of MRP2 and MRP3 may provide an explanation of how the products of phase II conjugation are effluxed from gallbladder epithelia. METHODS: Expression and localization of MRP2 and MRP3 were analyzed by reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence microscopy of human gallbladder tissue. RESULTS: Expression of MRP2 and MRP3 was identified in all gallbladders by RT-PCR followed by sequencing of the amplified fragments. Double immunofluorescence microscopy using 2 specific antibodies for the respective MRP isoform showed the simultaneous expression of MRP2 in the apical membrane and MRP3 in the basolateral membrane of gallbladder epithelia. MRP1 protein expression was not detectable. CONCLUSIONS: Our findings show the expression of MRP2 and MRP3 in distinct plasma membrane domains of gallbladder epithelia and provide evidence for the capacity of the gallbladder to secrete xenobiotic and endogenous anionic conjugates into blood via MRP3 and into bile via MRP2.

[Results of combined divergence operation in intermittent exotropia in 120 children]. / Ergebnisse der kombinierten Divergenzoperation bei intermittierender Exotropie bei 120 Kindern.

BACKGROUND: Intermittent exotropia is the most frequent indication for surgical correction of exodeviations in childhood. Overcorrection with prolongated or persistent consecutive esotropia can impair binocular vision particularly in early childhood. We wanted to investigate this potential risk and the dose/effect relation of recess-resect surgery on children. PATIENTS AND METHODS: 120 children up to ten years of age underwent recess-resect surgery for intermittent exotropia in our clinic from 1991 to 1999 (< 2% of the surgical cases). The cycloplegic refraction was spectacle corrected with a reduction of 0.5 dpt. Preoperatively, a diagnostic occlusion was performed for three days. The amount of surgery was calculated using our dosage schedules based on effects one week postoperatively. The squint angles as measured by the alternate prism and cover test at 5 m and 0.3 m pre- and 3 months postoperatively and the binocular functions as measured by the Bagolini striated glasses, Titmus, Randot, TNO, or Lang tests were evaluated. RESULTS: (Medians) Squint angles in primary position were: preoperative: distance (5 m)--15 degrees, near (0.3 m)--16 degrees; postoperative (n = 104); distance--4 degrees, near--3 degrees. Effectivity of surgery: distance: 1.3 degrees/mm, near 1.4 degrees/mm. Consecutive esotropia requiring surgical correction occurred in 1 child. Second surgery for intermittent exotropia in the years 1991 to 1999 was necessary in 5 children. Binocular functions (n = 95): Preoperative = postoperative: 61%, postoperative > preoperative 21%, postoperative < preoperative 18%. The diagnostic occlusion was helpful to differentiate "pseudo-divergence excess type" from "divergence excess type" exotropia. The average deviation did not increase under the diagnostic occlusion. The effectivity of surgery (degree/mm) in the children group was lower than in a compared group of older patients (> 10 years) with intermittent exotropia. CONCLUSION: Using our own dosage schedules and surgical technique, residual exodeviations are common after recess-resect surgery in childhood. The risk of consecutive esotropia or persistent impairment of binocular vision is low.

Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome.

BACKGROUND & AIMS: The Dubin-Johnson syndrome is characterized by conjugated hyperbilirubinemia and by impaired secretion of anionic conjugates from hepatocytes into bile. Absence of the multidrug-resistance protein 2 (MRP2; symbol ABCC2), an adenosine triphosphate-dependent conjugate export pump, from the hepatocyte canalicular membrane is the molecular basis of this syndrome. The aim of this study was the elucidation of all exon-intron boundaries of the MRP2 gene as a prerequisite for the analysis of mutations in patients with Dubin-Johnson syndrome. METHODS: Exon-intron boundaries of MRP2 were determined, and the amplified exons were screened for mutations. Immunofluorescence microscopy served to localize the MRP2 protein in human liver. RESULTS: The human MRP2 gene is approximately 45 kilobases long; it contains 32 exons and a high proportion of class 0 introns. In 2 patients with Dubin-Johnson syndrome, we detected a nonsense mutation at codon 1066 and a 6-nucleotide deletion mutation affecting codons 1392-1394. The MRP2 protein was absent from the canalicular membrane of both patients. CONCLUSIONS: The mutations detected so far show that various mutations in the MRP2 gene can lead to the Dubin-Johnson syndrome. The exon-intron boundaries established in this article will facilitate the analysis of additional mutations in the MRP2 gene.

Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane.

Several members of the multidrug resistance protein (MRP) family are expressed in the liver. Adenosine triphosphate (ATP)-dependent transport of glutathione and glucuronoside conjugates across the hepatocyte canalicular membrane is mediated by the apical MRP isoform, MRP2 (APMRP), also known as canalicular multispecific organic anion transporter (cMOAT). We have cloned an additional MRP isoform, MRP3, from human liver and localized it to the basolateral membrane domain of hepatocytes. Basolateral MRP (BLMRP) is composed of 1,527 amino acids and encoded by 4,581 base pairs of complementary DNA. Northern blotting of various human tissues indicated an expression of MRP3 in the liver, colon, pancreas, and, at a lower level, in the kidney. The amino acid identity of MRP3 with MRP1 and MRP2 is 58% and 48%, respectively. These three isoforms, encoded by genes on different chromosomes, have a similar predicted topology of transmembrane segments and ATP-binding domains. Antibodies raised against two peptide sequences of MRP3 that are not shared by other MRP family members detected recombinant MRP3 expressed in polarized MDCK cells. Both antibodies served to localize MRP3 to the basolateral membrane of hepatocytes. Double-label immunofluorescence microscopy confirmed that MRP3 was not detectable in the canalicular membrane domain. A particularly strong expression of the MRP3 protein was observed in the basolateral hepatocyte membrane of two patients with Dubin-Johnson syndrome who are deficient in MRP2. These results indicate that the basolateral MRP isoform, MRP3, may be upregulated when the canalicular secretion of anionic conjugates by MRP2 is impaired.

Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis.

Administration of phalloidin, one of the toxic peptides of the mushroom Amanita phalloides, leads to rapid and sustained cholestasis in rats. Although attributed to the interaction of phalloidin with microfilaments, the events leading to cholestasis are incompletely understood. The adenosine triphosphate (ATP)-dependent, apical conjugate export pump, termed multidrug resistance protein 2 (Mrp2) or canalicular multispecific organic anion transporter, is the major driving force for bile salt-independent bile flow. We investigated the role of Mrp2 in phalloidin-induced cholestasis. Bile flow decreased to 53% and 31% of control at 15 and 30 minutes after phalloidin (0.5 mg/kg), respectively. Mrp2-mediated [3H]leukotriene excretion into bile during the initial 45 minutes was reduced to 44% of control when [3H]LTC4 was injected 15 minutes after phalloidin treatment. Mrp2 was progressively lost from the hepatocyte canalicular membrane and detected predominantly on intracellular membrane structures together with other canalicular proteins including P-glycoproteins, ecto-ATPase, and dipeptidyl-peptidase IV. By contrast, structures involved in intercellular adhesion (zonula occludens, zonula adhaerens, and desmosomes) as well as intermediate filaments of the cytokeratin type appeared largely unaffected within 30 minutes after phalloidin. In line with the immunofluorescence analysis, immunoblots indicated a loss of Mrp2 and P-glycoproteins from the canalicular membrane and a 3- and 4.6-fold increase of these transport proteins in the microsomal fraction, respectively. Our results indicate that phalloidin induces marked alterations of the hepatocyte canalicular architecture and a loss of Mrp2 together with other proteins from the canalicular membrane. The resulting cholestasis can therefore be explained in part by the loss of export pumps, including Mrp2, from the canalicular membrane.

Enhanced virus resistance of transgenic mice expressing the human MxA protein.

MxA is a GTPase that accumulates to high levels in the cytoplasm of interferon-treated human cells. Expression of MxA cDNA confers to transfected cell lines a high degree of resistance against several RNA viruses, including influenza, measles, vesicular stomatitis, and Thogoto viruses. We have now generated transgenic mice that express MxA cDNA in the brain and other organs under the control of a constitutive promoter. Embryonic fibroblasts derived from the transgenic mice were nonpermissive for Thogoto virus and showed reduced susceptibility for influenza A and vesicular stomatitis viruses. The transgenic animals survived challenges with high doses of Thogoto virus by the intracerebral or intraperitoneal route. Furthermore, the transgenic mice were more resistant than their nontransgenic littermates to intracerebral infections with influenza A and vesicular stomatitis viruses. These results demonstrate that MxA is a powerful antiviral agent in vivo, indicating that it may protect humans from the deleterious effects of infections with certain viral pathogens.

Tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1.

We show that tick-transmitted Thogoto virus is sensitive to interferon-induced nuclear Mx1 protein, which is known for its specific antiviral action against orthomyxoviruses. Influenza virus-susceptible BALB/c mice (lacking a functional Mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of Thogoto virus. In contrast, Mx1-positive congenic, influenza virus-resistant BALB.A2G-Mx1 mice remained healthy and survived. Likewise, A2G, congenic B6.A2G-Mx1 and CBA.T9-Mx1 mice (derived from influenza virus-resistant wild mice) as well as Mx1-transgenic 979 mice proved to be resistant. Peritoneal macrophages and interferon-treated embryo cells from resistant mice exhibited the same resistance phenotype in vitro. Moreover, stable lines of transfected mouse 3T3 cells that constitutively express Mx1 protein showed increased resistance to Thogoto virus infection. We conclude that an Mx1-sensitive step has been conserved during evolution of orthomyxoviruses and suggest that the Mx1 gene in rodents may serve to combat infections by influenza virus-like arboviruses.

[The force transmission of positioners in different degrees of incisor protrusion. An in-vitro study]. / Die Kraftabgabe von Positionern bei unterschiedlicher Schneidezahnprotrusion. Eine In-vitro-Untersuchung.

The purpose of this study was to examine the forces exerted on protruded upper incisors by tooth positioners. Methodologically an in vitro force measurement model was used. The tooth positioners were made of 7 readily available materials commonly used in orthodontics. The study found that the values of the forces, which ranged from 0.4 N to 14.0 N per tooth, are dependent on the material used and the degree of tooth protrusion. In addition, the study analyzed the changes in force over a 3-month period during which time the positioners were stored at 37 degrees +/- 1 degree C in an aqueous environment. This environment corresponds closely to that found in the mouth.

[Especially gifted: especially happy, especially satisfied? On the self-concept of highly gifted and average children]. / Besonders begabt: besonders glücklich, besonders zufrieden? Zum Selbstkonzept hoch- und durchschnittlich begabter Kinder.

This study investigates the relation between intelligence and self-concept. 287 fourth-grade elementary-school students (151 intellectually gifted children and 136 children of average intelligence) participating in the Marburg Giftedness Project responded to an extended version of the Piers-Harris Children's Self-Concept Scale. Results show that gifted children score higher in all facets of self-concept. However, this difference is only in the scale "intellectual and school status" statistically significant. Compared with gifted and non-gifted "achievers", gifted "underachievers" score lower in most self-concept facets. Independently of their intelligence level, children of this age group have developed a very positive self-concept.

[The materials properties of the stock for positioners--an in-vitro study. I. The elastic behavior]. / Materialeigenschaften der Werkstoffe für Positioner--eine In-vitro-Untersuchung. I. Das elastische Verhalten.

The purpose of this study was to compare the physical and mechanical properties of materials for tooth positioners. 15 of these materials are in general use and four are experimental. Tensile strength at 20% elongation was observed and analyzed over a three-month period during which time the specimens were stored at 37 degrees +/- 1 degree C in an aqueous environment. The values of tensile strength covered a range from 24.9 MPa to 1.5 MPa depending on the particular material. Most of the materials displayed an increase in the module of elasticity over three-month period, but this increase was statistically significant in only one material (t-test, pmax < 0.00005).