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Publications and source records attributed to A Marx.
Mediastinal lipomas are slowly growing tumours. Only very few cases have been reported in children. None of these included a rapidly enlarging lipoma. We present an 8-year-old severely adipose girl with an incidentally diagnosed mediastinal lipoma that showed rapid enlargement within 7 weeks.
The main reason for myocardial dysfunction is chronical myocardial ischemia. Recently we could show, that NCAM (CD56), a neural cell adhesion molecule and member of the immunoglobuline superfamily, and the transcription factor AML1 (RUNX1) are overexpressed in chronic ischemic human heart failure compaired to normal hearts. Here we demonstrate, that the overexpression of NCAM (CD56) is specific for ischemic damage as compaired to other heart diseases including congestive cardiomyopathy, hypertrophic obstrutive cardiomyopathy, myocarditis and sarcoidosis. Concerning the transcriptional regulation of NCAM (CD56) by AML1 (RUNX1) we isolated 3 novel isoforms of AML 1 (RUNX1) with different transactivating function, that might be a regulatory element of the NCAM (CD56) overexpression in chronical myocardial ischemia.
Necrotizing sarcoid granulomatosis (NSG) is characterized by pulmonary nodular infiltrates, a typical histology, and a benign clinical course. The etiology and pathogenesis of the disease are still unknown. In childhood, it is extremely rare, with only three reported cases so far. Here we report on an 8-year-old girl, who to our knowledge is the youngest reported patient with NSG. The girl presented with shortness of breath and a sore throat. Chest X-ray and computed tomography (CT) scan revealed multiple nodular opacities of the lung. The symptoms and radiological findings disappeared within 6 months without any treatment. The diagnosis was based on the typical signs and symptoms of NSG and on the exclusion of other diseases. As abnormal immunological findings such as the lack of specific diphtheria antibodies in spite of vaccination against diphtheria were present, we suggest that immunologic mechanisms could play an etiologic role in the pathogenesis of NSG. In addition, the ratio of CD4+/CD8+ T-cells in the peripheral blood was significantly reduced, whereas the CD4+/CD8+ T-cell ratio in the immunohistochemical staining of the lung tissue was elevated. Since this compartmentalization is a typical finding in sarcoidosis, it supports the theory that NSG may represent a variant of sarcoidosis. However, because some characteristics of NSG are uncommon in typical sarcoidosis, NSG may also be an entity in its own right.
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OBJECTIVE: There are several differential diagnoses for acute abdominal discomfort with pain referred to the right lower quadrant region. The objective of this report is to outline our experience with diverticulitis of the caecum, which is a rare condition that is particularly difficult to diagnose correctly pre-operatively. METHODS: A retrospective analysis of acute diverticulitis of the caecum was performed over the period from January 1992 to December 2000 within the Surgical Department of the RWTH Aachen, Germany. The progress of each patient was assessed by interviewing the patient and by telephone contact with the patient's general practitioner. RESULTS: Seven patients with isolated infective diverticulitis of the caecum were encountered in the course of this study. In five of these cases, the pre-operative diagnosis was either unclear or incorrect. Four patients underwent surgery for suspected appendicitis. In one patient, the diverticulitis was diagnosed during laparoscopic surgery undertaken for presumed adnexal disease. Intestinal continuity was restored in all cases. The postoperative course was uneventful. CONCLUSIONS: Right-sided caecal diverticulitis is rare in comparison to diverticulitis of the sigmoid or descending colon. Nevertheless, it should be actively considered in the differential diagnosis of patients with acute tenderness in the right lower abdominal region.
A boy of Caucasian origin with a new subtype of autoimmune lymphoproliferative syndrome (ALPS) is described. The clinical picture was dominated by chronic noninfectious lymphadenopathy, splenomegaly, and recurrent bacterial infections. At the age of 6 the patient died of pneumococcal meningitis. Laboratory investigation disclosed impaired apoptosis in both B- and T-lymphocyte subsets and expanded populations of CD3+CD4-CD8- T lymphocytes. Furthermore, marked dysregulation of humoral immune responses with transient expansion of monoclonal B cells, corresponding monoclonal gammopathy, and the presence of autoantibodies was found. Functional and molecular analysis revealed that Fas protein expression was normal, a mutation in the Fas gene was not found. Moreover, transcription of the downstream effector caspase-10 was unremarkable. This patient is unique compared to previously described patients as severe humoral immunodeficiency and monoclonal gammopathy are usually not described in patients with ALPS. This case points out the important role of apoptosis in regulating the degree of humoral immune responses at a clonal level in humans and gives further evidence for the phenotypic diversity of ALPS.
Glomus organs are arteriovenous anastomoses which control the thermoregulation of the extremities. Benign tumors of these glomus organs, termed "glomangiomas", are therefore most frequently located in the fingers and toes. Case reports of primary glomangiomas in the respiratory- and gastrointestinal tracts as well as in the genital organs have been published. On the other hand, glomus tumors of the liver have not yet been described. We report the case of a 61-year-old patient with a smooth subcapsular lesion within the liver detected by a routine ultrasound scan. Further diagnostic imaging did not match with one of the common liver tumors. The diagnosis of a glomangioma was finally made by liver biopsy and subsequent histology. A review of the literature revealed a potential transformation of glomangiomas. Since the patient reported on inappetence weight loss and the tumor showed growth tendency, the indication for surgical excision was made. Final histologic investigation revealed no signs of malignancy. The primary glomangioma of the liver is a new differential diagnosis of benign liver tumors. As there is a possibility of malignant degeneration, we propose the decision for surgical removal once there are clinical symptoms and a growth tendency of the lesion.
BACKGROUND: Distant healing as a treatment modality is frequently used by patients and healers. Some preliminary evidence suggests possible effects. Since patients suffering from multiple chemical sensitivity and chronic fatigue syndrome have only few effective treatment options, distant healing will be offered as a treatment within a formal trial of distant healing. DESIGN AND METHOD: A four-armed randomized trial will include 400 patients with self-attributed, environmental problems who fulfil the diagnostic criteria of severe idiopathic chronic fatigue, chronic fatigue syndrome or multiple chemical sensitivity. Patients will be recruited by specialized general practitioners and environmental clinics. They will be treated by healers distributed all over Europe, coming from various healing traditions and nationalities. Each patient will be treated by 3 healers. Healers will have no contact with the patients and will only be provided with the patient's Christian name and a photograph. The patients will be randomized to one of 4 groups in a 2 x 2 factorial design. They will either receive (distant) healing or not, and either know or not know this decision. Thereby the effects of expectation and of time can be disentangled from the specific effects of healing. OUTCOME MEASURE: Primary outcome measure will be the mental health summary scale of the MOS SF-36. The measure will be taken at the beginning and at the end of a 6- month treating or waiting period, respectively. A variety of moderator variables will be considered to evaluate which of these may be predictive of outcome.
In patients with pulmonary emphysema, studies have reported 2-3% of individuals with severe alpha1-Pi deficiency. The aims of this study were to evaluate the accuracy of a new method for quantifying alpha1-Pi through phenotyping from dried blood spots (DBS) and to test the hypothesis that the screening of a population at risk increases the detection rate for severe alpha1-Pi deficiency. The accuracy of phenotyping results from DBS was compared to conventional methods in a total of 555 individuals. In a prospective study 1,060 patients with chronic lung disease were screened for alpha1-Pi deficiency using DBS. The validation of the phenotyping method from DBS showed an accuracy of 100%. Out of 1,060 tested patients, none had a severe PiZ deficiency and only 3 had PiSZ, whilst 36 (3.34%) individuals were identified as heterozygous for PiMS and 39 (3.68%) for PiMZ. No patients with severe alpha1-Pi deficiency could be detected in this population and the frequency of PiMS or PiMZ detected was similar to that of the normal population. Thus, the screening of an unselected population of chronic obstructive pulmonary disease and asthma patients may not detect a large number of individuals with severe alpha1-Pi deficiency.
Extrahepatic bile duct disease is a rare finding in infancy and early childhood. However, there is an increasing number of patients operated at this age reported in the literature. This increase may have multifactorial reasons, e.g. real increase, better ability of detection as a result of better diagnostic techniques and knowledge of predisposing factors of extrahepatic bile duct disease in childhood, especially in early childhood and infancy. The following report describes three cases of extrahepatic bile duct disease in infancy and early childhood treated at the Department of Surgery of the University of Technology in Aachen, Germany. From 1986 to 1998 28 Patients below 18 years were operated at our Department of Surgery. There was a recognizable increase of patients in 1996, 1997 and 1998. Whereas from 1986 to 1995 an average of 1.5 Cholecystectomies in pediatric patients were done, the years from 1996 to 1998 show an average of 5,33 patients operated per year. Every patient obtained a Cholecystectomy -- 15 conventional open Cholecystectomies and 13 Laparoscopies, which were primarily performed in children in our clinic in 1991. Besides cholecystectomy in one case a Hepaticoenterostomy was necessary and in another case surgical treatment of the Papilla of Vater and the Common Bile Duct was performed. In 22 patients symptomatic Cholelithiasis was the indication for a Cholecystectomy. Another Patient had a gallbladder polyp consisting of heterotopic Duodenal glands, two patients showed a shock gallbladder following trauma and cardiac operation and three patients had chronic Cholecystitis without gallstones. Clinical data was collected and retrospectively reviewed. Additionally, we created a personal questionnaire to carry through a follow-up. Three Patients were less than 3 1/2 years old. The youngest patient was only 5 months old and presented with Cholelithiasis and Choledocholithiasis. Another male patient, aged 2 years received a Cholecystectomy and a Hepaticoenterostomy because of a Choledochal Cyst Type Ib (Todani-Classification). And a 3-year-old-girl had a shock gallbladder caused by thromboembolism following cardiac operation nine days before.
We determined the crystal structure of the motor domain of the fast fungal kinesin from Neurospora crassa (NcKin). The structure has several unique features. (i) Loop 11 in the switch 2 region is ordered and enables one to describe the complete nucleotide-binding pocket, including three inter-switch salt bridges between switch 1 and 2. (ii) Loop 9 in the switch 1 region bends outwards, making the nucleotide-binding pocket very wide. The displacement in switch 1 resembles that of the G-protein ras complexed with its guanosine nucleotide exchange factor. (iii) Loop 5 in the entrance to the nucleotide-binding pocket is remarkably long and interacts with the ribose of ATP. (iv) The linker and neck region is not well defined, indicating that it is mobile. (v) Image reconstructions of ice-embedded microtubules decorated with NcKin show that it interacts with several tubulin subunits, including a central beta-tubulin monomer and the two flanking alpha-tubulin monomers within the microtubule protofilament. Comparison of NcKin with other kinesins, myosin and G-proteins suggests that the rate-limiting step of ADP release is accelerated in the fungal kinesin and accounts for the unusually high velocity and ATPase activity.
The microtubule-associated protein tau is a natively unfolded protein in solution, yet it is able to polymerize into the ordered paired helical filaments (PHF) of Alzheimer's disease. In the splice isoforms lacking exon 10, this process is facilitated by the formation of beta-structure around the hexapeptide motif PHF6 ((306)VQIVYK(311)) encoded by exon 11. We have investigated the structural requirements for PHF polymerization in the context of adult tau isoforms containing four repeats (including exon 10). In addition to the PHF6 motif there exists a related PHF6* motif ((275)VQIINK(280)) in the repeat encoded by the alternatively spliced exon 10. We show that this PHF6* motif also promotes aggregation by the formation of beta-structure and that there is a cross-talk between the two hexapeptide motifs during PHF aggregation. We also show that two of the tau mutations found in hereditary frontotemporal dementias, DeltaK280 and P301L, have a much stronger tendency for PHF aggregation which correlates with their high propensity for beta-structure around the hexapeptide motifs.
Lymphomas were studied in kindreds with autoimmune lymphoproliferative syndrome (ALPS; Canale-Smith syndrome), a disorder of lymphocyte homeostasis usually associated with germline Fas mutations. Fas (CD95/APO-1) is a cell surface receptor that initiates programmed cell death, or apoptosis, of activated lymphocytes. Lymphoma phenotype was determined by immunohistochemistry, frequency of CD3(+)CD4(-)CD8(-) T-cell-receptor alpha/beta cells by flow cytometry, nucleotide sequences of the gene encoding Fas (APT1, TNFRSF6), and the percentage of lymphocytes undergoing apoptosis in vitro. Of 223 members of 39 families, 130 individuals possessed heterozygous germline Fas mutations. Eleven B-cell and T-cell lymphomas of diverse types developed in 10 individuals with mutations in 8 families, up to 48 years after lymphoproliferation was first documented. Their risk of non-Hodgkin and Hodgkin lymphomas, respectively, was 14 and 51 times greater than expected (each P <.001). Investigation of these 10 patients and their relatives with Fas mutations revealed that all had defective lymphocyte apoptosis and most had other features of ALPS. The tumor cells retained the heterozygous Fas mutations found in the peripheral blood and manifested defective Fas-mediated killing. These data implicate a role for Fas-mediated apoptosis in preventing B-cell and T-cell lymphomas. Inherited defects in receptor-mediated lymphocyte apoptosis represent a newly appreciated risk factor for lymphomas.
We investigated Danaparoid Sodium (Orgaran) as anticoagulant using three different concentrations (9, 4,5 or 3 U/ml anticoagulant solution) for the use in the autotransfusion device Cell Saver 5 (Haemonetics). Fresh units of whole blood packs were mixed in the reservoir in a proportion of 5:1 with the anticoagulant solution. Having started the Cell Saver 5 in the automatic mode, the amount of Danaparoid in the retransfusion blood was determined (chromogenic Antifactor-Xa test). The lowest concentration of the anticoagulant was applied in 4 patients with Heparin-induced Thrombocytopenia Type II undergoing total hip arthroplasty. There was a correlation between the concentration in the reservoir and in the retransfusion blood. None of the patients showed a disturbance of his coagulation system. One of them had slight clotting in the reservoir. We recommend the use of the lower concentrations tested: 4,5 U/ml or, particularly for patients with renal insufficiency or low body weight or expected high retransfusion volumes, 3 U/ml as anticoagulant concentrations. If the autotransfusion device is used according to the manufacturer's instructions there may be virtually no risk of clotting in the Cell Saver or of inhibition of the coagulation system in the patient.
To investigate genetic abnormalities associated with the development of thymic epithelial tumors, we performed microsatellite analysis of 26 thymomas belonging to three different World Health Organization types (A, B3, and C) using 48 repeats. The most frequent aberration seen was loss of heterozygosity (LOH) in the region 6q23.3-25.3 detected in 11 tumors (45.8% of informative cases). Further consistent LOHs were detected in regions 3p22-24.2, 3p14.2 (FHIT gene locus), 5q21 (APC), 6p21, 6q21-22.1, 7p21-22, 8q11.21-23, 13q14 (RB), and 17p13.1 (p53). Microsatellite instability was extremely rare, occurring in one type B3 thymoma only, although, at 12.5% of the analyzed loci. Comparing the allelotypes of the analyzed thymomas, we were able to identify two pathogenetic pathways these tumors develop along, characterized by the 6q23.3-25.3 and 5q21 LOHs, respectively. The APC aberration on 5q21 showed significant associations with LOH in the 3p22-24.2, 13q14, and 17p13.1 regions. Interestingly, type A thymomas presented with consistent LOH in the region 6q23.3-25.5 only, they did not reveal any aberrations in the APC, RB, and p53 gene loci or regions 3p22-24.2 and 8q11.21-23. The absence of these aberrations might be the reason for the well-known benign behavior of type A thymomas as compared to types B3 and C tumors.
Monoclonal antibodies were developed against vitellogenin (vtg) of rainbow trout. This protein is used as a biochemical response to the exposure with estrogenic compounds. Several mice were immunized with purified vtg and the spleen cells of these mice were fused with myeloma cells. The resulting hybridoma cells were screened with an enzyme immunoassay for the production of specific anti-vtg antibodies. Twelve positive cell lines were detected. The hybridoma cell line B8D8 was adjusted to serum free medium; it produced monoclonal antibodies with a high selectivity and sensitivity. A detection limit of 5 microg/l vtg was achieved with a competitive enzyme immunoassay applying a preincubation step and a streptavidin-biotin amplification system (ABC system). Cross-reactivity with vtg of other species was detected with roach (Rutilus rutilus), flounder (Platichthys flesus) and dab (Limanda limanda). The assay was applied to rainbow trout (Oncorhynchus mykiss), which were exposed for six months to defined concentrations of effluents (10%, 20%, 30% and 40%) and surface water. Increased vtg levels in male fish are correlated with the increasing levels of effluent. The effluent levels in the exposure experiments are relevant for effluent loadings of the Berlin waterways during the seasons of the year.
The T cell death associated gene 51 (TDAG51) was shown to be required for T cell receptor (TCR)-dependent induction of Fas/Apo1/CD95 expression in a murine T cell hybridoma. Despite the absence of a nuclear localization sequence and a nucleic acid binding domain, it was suggested to be localized in the nucleus and to function as a transcription factor regulating Fas-expression. However, we demonstrate that the human (h)TDAG51 protein is localized in the cytoplasm and the nucleoli, suggesting a role in ribosome biogenesis and/or translation regulation. Indeed, it strongly inhibited translation of a luciferase mRNA in a reticulocyte translational extract. Furthermore, cotransfection of hTDAG51 and the luciferase gene into 293T cells resulted in a strong inhibition of luciferase mRNA translation. Our findings were further strengthened by isolating in a yeast two-hybrid screen three proteins which are involved in the regulation of translation. We speculate that hTDAG51 couples TCR signaling to inhibition of protein biosynthesis in activated T lymphocytes.
UNLABELLED: Former studies demonstrated that small amounts of heparin might remain in the prepared retransfusion blood during intraoperative autotransfusion. This could lead to serious complications in patients suffering from heparin-induced-thrombocytopenia type II (HIT II). Lepirudin is an approved anticoagulant in HIT II-patients. We studied to what extent lepirudin is washed out during the preparation of retransfusion blood, when it is used as anticoagulant for the autotransfusion device cell saver 5. METHODS: We investigated four different concentrations of lepirudin solutions, 5 mg, 10 mg, 20 mg and 30 mg per litre normal saline. In order to imitate a clinical situation, each lepirudin solution was mixed with human blood in a 1:5-ratio and put into the reservoir of the cell saver. The device was started in the automatic mode using 1000 ml saline as washing solution. Several runs were carried out (five times using the 5 mg/l solution, ten times the 10 mg/l, eleven times the 20 mg/l and eleven times the 30 mg/l solution). The lepirudin concentration in the prepared retransfusion blood was measured. RESULTS: The median percentage reduction of the lepirudin content from the reservoir blood to the retransfusion blood was 100% for the 5 mg/l, 90.4% for the 10 mg/l, 94.3% for the 20 mg/l and 86.3% for the 30 mg/l solution. The differences of percentage reduction are not significant. But the different lepirudin concentrations in the anticoagulant solution have a significant influence on the lepirudin concentration in the retransfusion blood. The lepirudin concentration (median) in the retransfusion blood was 0.00 microgram/ml for the 5 mg/l, 0.16 microgram/ml for the 10 mg/l, 0.19 microgram/ml for the 20 mg/l and 0.66 microgram/l for the 30 mg/l lepirudin solution. CONCLUSION: Lepirudin as an anticoagulant for intraoperative autotransfusion is effectively eliminated using the cell saver 5 device in the automatic mode with 1000 ml saline as washing solution. A clinically relevant disturbance of coagulation is not to be expected, even if the highest concentration of lepirudin anticoagulant solution investigated in this study is used.