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M Manns

Publications and source records attributed to M Manns.

At least 19 recordsLinked to original sources
PubMed2004

Post-hatch activity-dependent modulation of visual asymmetry formation in pigeons.

The embryonically induced visual lateralization in pigeons can be modified by occlusion of one eye after hatching. Here we show that this deprivation effect could be also attained by short-term blocking of retinal activity with tetrodotoxin (TTX), leading to a dominance of the ipsilateral hemisphere in a visual discrimination task. This lateralization pattern resulted from a performance increase conveyed by the non-deprived hemisphere, while performance with the TTX-injected eye did not differ from that of saline-injected controls. Thus, post-hatch modulation of visual lateralization is mediated by TTX-sensitive, activity-dependent neuronal mechanisms. The transient silencing of one visual input alters the activity balance between the left and right eye system, enhancing visuoperceptive skills in the relatively higher active hemisphere.

Animals↗
PubMed2003

[Ultrasound of acute abdomen].

Ultrasound is an important tool in the diagnosis of acute abdominal pain, which is mainly caused by gastrointestinal diseases. This article gives an overview on the important differential diagnosis related to pain localization. Sonomorphological signs and their sensitivity and specificity are discussed. In contrast to other imaging methods ultrasound is hand guided. The present article differentiates the diagnostic capability of ultrasonic diagnosis depending on technical equipment and sonographer's educational level. These facts are important to stabilize the position of ultrasound in the ensemble of other imaging methods. The use of mobile ultrasound machines and an improved training (e.g. by computer assisted sonosimulator systems) will lead to an increasing importance of ultrasound.

Abdomen↗
PubMed2003

Simulation of abdomen sonography. Evaluation of a new ultrasound simulator.

AIM: We developed and evaluated a simulator for the sonography of the abdomen in order to improve the teaching quality in sonography training. METHOD: Eleven medicine residents who had received 4 to 12 months full time sonography training performed ultrasound examinations of the right upper quadrant in 5 consecutive patients and in 5 simulator cases. The correctness of their findings and the time required for the examinations were measured. The subjective confidence in their findings and the handling of the ultrasound machines were rated on a visual analogue scale. RESULTS: During patient ultrasound examination 75 % (SEM 9%) of all pathologic findings were recognized by the residents, whereas 71 % (SEM 8%) of the pathologies of the simulator cases were found. This minimal difference was not significant in the paired, two sided t-test (p = 0.15). Severe pathologies did not escape detection. The time required for patient examination(10.57 min, SEM 3.25 min) was not significantly different (p = 0.53) to the time required for the simulator cases (9.59 min, SEM 2.98 min). The subjective confidence in the sonographic findings did not differ significantly (p = 0.39) between the real patient situation (68%, SEM 6%) and the simulation (64%, SEM 12 %). Only the handling of the ultrasound machines was judged to be significantly better (p=0.008) than the simulator (74%,SEM 7% vs. 61 %, SEM 12%). CONCLUSION: In this first direct crossover comparison between real patient sonography and simulator based scanning we proved that the simulator we developed simulates the real patient examination reliably and reproducibly.

Abdomen↗
PubMed2001

Nucleus isthmi, pars semilunaris as a key component of the tectofugal visual system in pigeons.

The avian isthmic nuclei are constituted by a group of structures reciprocally connected with the tectum opticum and considered to play a role in the modulation of intratectal processes. Although the two larger isthmic nuclei, the n. isthmi pars parvocellularis (Ipc) and the n. isthmi pars magnocellularis (Imc), have been studied in detail previously, the third and smallest of this group, the n. isthmi pars semilunaris (SLu), has been largely neglected. The present study demonstrates this isthmic component to be characterized by a unique connectivity and immunohistochemical pattern: 1) SLu receives tectal afferents and projects back onto the outer retinorecipient tectal layers; 2) it projects bilaterally onto the nucleus rotundus and thus modulates the ascending tectofugal system; 3) in addition, previous studies have demonstrated SLu projections onto the lateral spiriform nucleus (SpL), which mediates basal ganglia output onto the tectum. In that SpL projects onto the deep layers of the tectum, SLu indirectly modulates descending tectal output patterns. Taken together, the role of SLu goes far beyond a local modulation of intratectal processes. Instead, this isthmic structure is likely to play a key role in the topographically organized modulation of the ascending and, at least indirectly, also the descending projections of the optic tectum.

Animals↗
PubMed2001

Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications.

Adult↗
PubMed2001

In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.

Prolonged treatment of chronic hepatitis B virus (HBV) infection with lamivudine ([-]-beta-L-2',3'-dideoxy-3' thiacytidine) or famciclovir may select for viral mutants that are drug resistant due to point mutations in the polymerase gene. Determining whether such HBV mutants are sensitive to new antiviral agents is therefore important. We used a transient transfection system to compare the sensitivities of wild-type HBV and four lamivudine- and/or famciclovir-resistant HBV mutants to adefovir [9-(2-phosphonyl-methoxyethyl)-adenine; PMEA] and the nucleoside analogues (-)-beta-D-2, 6-diaminopurine dioxolane (DAPD) and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU). The drug-resistant mutants contained amino acid substitutions in the polymerase protein. We found that the M550I and M550V plus L526M substitutions, which confer lamivudine resistance, did not confer cross-resistance to adefovir or DAPD, but conferred cross-resistance to L-FMAU. The M550V substitution in isolation conferred a similar phenotype to M550I, except that it did not confer significant resistance to L-FMAU. The L526M substitution, which is associated with famciclovir resistance, conferred cross-resistance to L-FMAU but not to adefovir or DAPD. Inhibition of HBV secretion by DAPD, L-FMAU, and adefovir did not always correlate with inhibition of the generation of intracellular HBV replicative intermediates, suggesting that these analogs may preferentially inhibit specific stages of the viral replication cycle.

Adenine↗
PubMed2001

K-ras mutations in the bile of patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: The development of cholangiocarcinoma (CCC) is a complication of primary sclerosing cholangitis (PSC). To date, no reliable factors have been described which can define those PSC patients at high risk for the development of CCC and the clinical diagnosis of CCC in PSC patients is difficult. Therefore, molecular markers of cholangiocarcinogenesis, such as K-ras mutations, may improve the early diagnosis of CCC or the timing of liver transplantation. METHODS: K-ras mutations were analysed by enriched polymerase chain reaction/restriction fragment length polymorphism in the bile fluid of 56 PSC patients and 20 patients with other cholestatic diseases. To assess the value of K-ras mutations as a risk factor for cholangiocarcinogenesis, patients were prospectively investigated over a mean period of 31.5 months. RESULTS: In contrast with the control group, 17 (30%) patients with PSC revealed K-ras mutations in bile fluid. The mean Mayo score was not significantly different between PSC patients with (mean score 0.70) and without (mean score 0.13; p=0.2) K-ras mutations. In contrast with the group of PSC patients without K-ras mutations, four CCCs and two dysplasia were diagnosed in the group of patients with K-ras mutations during the follow up investigation (p<0.001). CONCLUSIONS: Our results indicate that K-ras mutations in bile fluid of PSC patients represent frequent early events during cholangiocarcinogenesis. However, most of the PSC patients with K-ras mutations remained tumour free after a long follow up investigation which is in agreement with the fact that these mutations are not specific for malignancy but may also occur in normal bile duct mucosa or in dysplasias. Therefore, analysis of K-ras mutations in bile should not be used for diagnosis of CCC in PSC patients. However, the results of our prospective follow up investigation indicate that K-ras mutations in bile fluid of PSC patients have to be considered as risk factors for the development of CCC which may have implications for the timing of liver transplantation.

Adult↗
PubMed2000

Asymmetry pays: visual lateralization improves discrimination success in pigeons.

Functional cerebral asymmetries, once thought to be exclusively human, are now accepted to be a widespread principle of brain organization in vertebrates [1]. The prevalence of lateralization makes it likely that it has some major advantage. Until now, however, conclusive evidence has been lacking. To analyze the relation between the extent of cerebral asymmetry and the degree of performance in visual foraging, we studied grain-grit discrimination success in pigeons, a species with a left hemisphere dominance for visual object processing [2,3]. The birds performed the task under left-eye, right-eye or binocular seeing conditions. In most animals, right-eye seeing was superior to left-eye seeing performance, and binocular performance was higher than each monocular level. The absolute difference between left- and right-eye levels was defined as a measure for the degree of visual asymmetry. Animals with higher asymmetries were more successful in discriminating grain from grit under binocular conditions. This shows that an increase in visual asymmetry enhances success in visually guided foraging. Possibly, asymmetries of the pigeon's visual system increase the computational speed of object recognition processes by concentrating them into one hemisphere while preventing the other side of the brain from initiating conflicting search sequences of its own.

Animals↗
PubMed2000

NFkappaB mediates apoptosis through transcriptional activation of Fas (CD95) in adenoviral hepatitis.

NFkappaB is an essential survival factor in several physiological conditions such as embryonal liver development and liver regeneration. However, NFkappaB is also a main mediator of the cellular response to a variety of extracellular stress stimuli, and it has been shown that some viral-induced host cell apoptosis appears to be dependent on NFkappaB activation. The activation of NFkappaB upon viral infection may be a rapid way of initiating an innate immune response against the viral particles. We have assessed the role of NFkB during the early phase of adenoviral hepatitis in a nude mouse model using an adenoviral vector expressing a mutant form of IkappaBalpha. Administration of a LacZ-expressing adenoviral vector induces NFkB DNA and correlates with the up-regulation of Fas (CD95) mRNA, but not FasL (CD95L) mRNA, during the early phase of adenoviral hepatitis. The rapid increase in NFkappaB DNA binding after adenoviral infection of the liver could be very effectively inhibited by IkappaBalpha. Compared with the LacZ control virus, the IkappaBalpha-expressing adenoviral vector inhibits the increase of Fas (CD95) mRNA expression, in particular in the very early phase of the hepatitis. Reporter gene experiments in hepatoma cell lines with a Fas promoter-luciferase construct indicated that the repression of Fas (CD95) mRNA by IkappaBalpha was transcriptionally mediated. The functional relevance of the NFkappaB-dependent increase in Fas (CD95) transcription was assessed by caspase 3 assays and terminal dUTP nick-end labeling tests. Compared with the control, IkappaBalpha adenoviral infection resulted in reduced caspase 3 activity during the early phase of viral hepatitis and in a prevention of liver cell apoptosis 24 h after adenoviral administration. Therefore our study demonstrates a new pro-apoptotic function of NFkappaB in Fas (CD95)-mediated apoptosis of hepatocytes. Interestingly, NFkappaB mediates liver cell apoptosis upon viral infection even in a phase where tumor necrosis factor-alpha is already induced, as shown by the time curves of tumor necrosis factor-alpha serum levels. Therefore, the pro- or anti-apoptotic role of NFkappaB appears to be more determined by the nature of the death stimulus than by the origin of the tissue.

Adenoviridae Infections↗
PubMed2000

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area.

AIMS/BACKGROUND: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. METHODS: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993-1997 were retrospectively studied. RESULTS: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9%) with HCV and 10% coinfection with HBV/HCV This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6%) had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5%) metastases in other organs be clinically diagnosed by chest X-ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 microg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. CONCLUSION: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.

Adult↗
PubMed2000

Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy.

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEXtrade mark bDNA, MONITOR AMPLICORtrade mark and SUPERQUANTtrade mark assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO-LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0. 456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut-offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.

Antiviral Agents↗
PubMed2000

Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation.

BACKGROUND & AIMS: Mutations of the cationic trypsinogen have been described in hereditary pancreatitis. We report a new trypsinogen mutation in the activation peptide of the proenzyme in a family with chronic pancreatitis. METHODS: The coding region of the cationic trypsinogen gene was sequenced after polymerase chain reaction amplification. The following peptides homologous to the N-terminal end of cationic trypsinogen were synthesized (one-letter code, mutated amino acid underlined): wild-type peptide, APFDDDDKIVGG; pD22G, APFDDDGKIVGG; pK23R, APFDDDDRIVGG. The sequences of pD22G and pK23R correspond to the recently identified mutation K23R and to the mutation described here (D22G). To mimic trypsinogen activation, these peptides were digested with trypsin for 30 minutes at pH 5.0-8. 0, and the fragments were analyzed by high-performance liquid chromatography. RESULTS: In a family with clinical evidence of hereditary chronic pancreatitis, a missense mutation of codon 22 (GAC-->GGC) of the cationic trypsinogen was found. This mutation results in a substitution of aspartic acid by glycine; therefore, the mutation was called D22G. Chromatographic analysis of tryptic digests of the peptides pD22G and pK23R showed hydrolysis rates of 22% and 75%, respectively, whereas the wild-type peptide was hydrolyzed at only 6%. The cleavage rates were reduced at lower pH, and no hydrolysis occurred without trypsin. CONCLUSIONS: The activation peptides of the trypsinogen variants D22G and K23R could be released at a higher rate than in wild-type trypsinogen, resulting in increased amounts of trypsin in the pancreas, which could initiate pancreatitis.

Adult↗
PubMed2000

Tumor necrosis factor alpha in the pathogenesis of human and murine fulminant hepatic failure.

BACKGROUND & AIMS: The tumor necrosis factor (TNF)-alpha/TNF receptor system is critical for liver development because hepatocytes undergo apoptosis if the antiapoptotic cascades resulting in RelA NF-kappaB activation are not effective. Therefore, we studied the role of TNF-alpha in fulminant hepatic failure (FHF) and developed a new therapeutic strategy. METHODS: Serum levels and hepatic expression of TNF-alpha and both TNF receptors were determined by enzyme-linked immunosorbent assay and immunohistochemistry. Adenoviral vectors were constructed expressing dominant-negative proteins interfering with intracellular TNF-alpha-dependent pathways. The relevance of these constructs was studied in primary mouse hepatocytes and in a murine model of FHF. RESULTS: Serum levels of TNF-alpha and TNF receptors are significantly increased in FHF; this increase correlates with patient prognosis. In livers of patients with FHF, infiltrating mononuclear cells express high amounts of TNF-alpha and hepatocytes overexpress TNF receptor 1 (TNF-R1). Apoptotic hepatocytes are significantly increased in FHF, and there is a strong correlation with TNF-alpha expression, which is even more pronounced in areas of mononuclear infiltrates. In an in vivo FHF model, the Fas-associated death domain (FADD), adenovirus selectively blocked the intracellular pathway, leading to mitochondrial cytochrome c release, caspase-3 activation, and, thus, apoptosis of hepatocytes. CONCLUSIONS: The results show that the TNF-alpha/TNF-R1 system is involved in the pathogenesis of FHF in humans. Studies in this animal model indicate that FADD may serve as a molecular target to prevent liver cell death in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed1999

p53 represses CAAT enhancer-binding protein (C/EBP)-dependent transcription of the albumin gene. A molecular mechanism involved in viral liver infection with implications for hepatocarcinogenesis.

p53 is a transcription factor that is activated by genotoxic stress and mediates cell cycle arrest and apoptosis. Here we demonstrate that infection of mouse liver with recombinant E1/E3-deleted adenovirus leads to p53 activation and simultaneously to the down-regulation of albumin gene expression. In vitro transcription assays indicate that transcriptional mechanisms mediated through the albumin promoter are responsible for reduced albumin mRNA levels during viral infection. Albumin expression is maintained in the liver by a combination of liver-enriched transcription factors such as CAAT enhancer-binding protein (C/EBP)alpha and C/EBPbeta. We show that p53 wild type and tumor-derived p53 mutations repress C/EBP-mediated transactivation of the albumin promoter. The binding of C/EBPalpha or -beta to its cognate sequence in the albumin promoter is not inhibited by p53 expression. Deletion analysis and domain swapping experiments show that repression of C/EBPbeta-mediated transactivation is dependent on the N-terminal domain of p53 and the transactivation domain, leucine zipper domain, and the inhibitory domain II (amino acids 163-191) of C/EBPbeta. Our results provide a molecular explanation for the p53-mediated down-regulation of liver-specific gene expression after viral infection. Additionally, as overexpression of p53 mutants is frequently found in undifferentiated hepatocellular carcinomas, the same mechanisms may contribute to the lack of liver-specific gene transcription in these tumors.

Albumins↗
PubMed1999

'Natural' and artificial monocular deprivation effects on thalamic soma sizes in pigeons.

The dominance for visual pattern analysis of the left hemisphere in normal pigeons and the concomitant morphological asymmetries in the optic tectum can be attributed to a 'natural' prehatch monocular deprivation of the left eye resulting from an asymmetrical embryonic position within the egg. Using control animals and pigeons which were monocularly deprived for 10 days after hatching, the present study could show that the cellular soma sizes of the nucleus rotundus within the tectofugal visual pathway are modified by light experience depending on the timepoint and direction of lateralized stimulation. Although rotundal cell size is thus ontogenetically modified in an activity-dependent manner, a detailed comparison makes it likely that the mechanisms which govern developmental plasticity of visual pathways differ between birds and mammals.

Animals↗
PubMed1999

Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation.

Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.

Adult↗