Biomedical subjects

R Ludwig

Publications and source records attributed to R Ludwig.

At least 55 records · Page 3Linked to original sources

PubMed1996

[Prognosis of shoulder calcifications after irrigation treatment and roentgen findings. A prospective study and literature review].

In 106 shoulder joints of 94 patients suffering from calcifying shoulder (calcifying tendinitis), needling and lavage were performed. Patients were prospectively investigated before and after treatment to examine if location, size, number and density of calcium deposits would predict outcome after the above-mentioned lavage. Excellent and good results were seen for subacromial calcifications and those situated near the tuberculum majus. Density and number of calcifications were without discriminating value, whereas large calcium deposits (> 1,5 cm) and fairly small calcifications (< 1,0 cm) responded very well to conservative treatment as described above.

Adult↗

PubMed1996

A new design for a three-channel surface gradient coil employing a three-dimensional finite element model.

A new design of a three-channel surface gradient coil (SGC) is presented. The optimal objective of this design is to minimize parasitic field gradients by modifying the wire arrangement in the individual coils. A 3D finite element (FE) model is employed to analyze the SGC's field predictions. The numerical analysis results of the new SGC design indicate improved field behaviors when compared with those of a previously reported SGC designed by Cho and Yi (J. Magn. Reson. 94, 471-485 (1991)). To confirm the predicted improvement, two Gy (Y-axis) gradient coils, based on the old and new designs, have been constructed and installed in a General Electric CSI 2 Tesla MRI system with a 15-cm bore. Based on the resulting MR images, the new gradient coil configuration provides more uniform field gradients and less parasitic field gradients, which results in higher quality images than the previously reported SGC design. This paper also demonstrates the remarkable accuracy of the 3D FE simulation model.

Computer Simulation↗

PubMed1996

Metabolism of neuropeptide Y and calcitonin gene-related peptide by cultivated neurons and glial cells.

Neuropeptide Y and calcitonin gene-related peptide are abundant neuropeptides in the mammalian central and peripheral nervous systems. Their enzymatic degradation by cultivated neurons, astrocytes, and microglia, as well as by purified urokinase-type plasminogen activator, plasmin, thrombin, and trypsin, was investigated in an in vitro approach to elucidate the role of matrix-degrading serine proteinases for inactivation of neuropeptides, especially those of higher amino acid chain length, in the brain. Astrocytes were almost unable to catabolize the peptides. Cultivated neurons and microglia digested neuropeptide Y through cleavage after Arg19, Arg25, Arg33, and Arg35, calcitonin gene-related peptide was cleaved after Arg11 and Arg18. The same cleavage pattern was observed, when neuropeptide Y and calcitonin gene-related peptide were degraded by purified urokinase-type plasminogen activator, plasmin, thrombin, and trypsin. For further characterization of the neuropeptide-degrading serine proteinase activities from cell cultures, urokinase-type plasminogen activator was identified on microglia by immunostaining, whereas tissue-type plasminogen activator mRNA occurred in neurons and astrocytes, but not in microglia. The data are consistent with the possibility that the neuropeptide-degrading serine proteinase activity on neurons and microglia is due to a mixture of plasmin and plasminogen activator activities.

Animals↗

PubMed1996

Time course of methotrexate polyglutamate formation and degradation in the pre-B-leukaemia cell line Nalm6 and in lymphoblasts from children with leukaemia.

With the aim of investigation, the mechanisms of resistance to methotrexate (MTX) in children refractory to leukaemia-treatment, we established a method of analysing MTX metabolism in Nalm6 cells (human pre-B). The optimal extracellular concentration for MTX uptake and MTX polyglutamate (MTXPG2-6) formation at a density of 5 x 10(6) cells/ml was 1 microM 3H-MTX. After 15 h incubation at this concentration, a plateau of 5 pmol/10(6) cells of total MTX accumulated in the form of equal amounts of polyglutamates 3, 4 and 5 and low amounts of MTX and polyglutamates 2 and 6. MTX preloaded cells rapidly lost MTX and MTXPG2 in MTX-free medium, while MTXPG5 was still formed and then degraded very slowly. After 8 h in medium without MTX, 40% of total MTXPG was lost, after 24 h, 70%. The method is feasible for patient blasts. The number of blasts isolated from bone marrow after diagnosis is enough to perform small kinetic studies. The uptake of MTX into patient blasts is about 1/10 of that in Nalm6 cells.

Antimetabolites, Antineoplastic↗

PubMed1996

[Resection of nephroblastoma: problems and complications--evaluation of the Nephroblastoma Study SIOP 9/GPOH].

The german SIOP 9/GPOH trial and study registered 486 patients with Wilms' tumor (1/89-3/94). Preoperative chemotherapy was the general approach. The indication for primary surgery was limited (age < 0.5 and > 16 years, uncertainty of diagnosis, emergency). Wilms' tumors were operated in 482 patients (4 died preoperatively) in 78 centres. Surgical and histological reports were analyzed concerning intra- and perioperative problems and complications. A total of 60% of pretreated and 39.8% of untreated tumors had local stage I. Nephroblastomas ruptured intraoperatively in 6.0% after pretreatment versus 11.5% in primary surgery. A tumor thrombus in the inferior vena cava complicated surgery in 3.1% of cases. A total of 14.3% of all histologically positive lymphnodes were correctly biopsied by the surgeon despite their normal macroscopic aspect. The overall rate of intra- and perioperative complications was low.

Adolescent↗

PubMed1995

Expression of resistance-related proteins in nephroblastoma after chemotherapy.

Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no preoperative chemotherapy. In untreated patients, no expression of P-glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P-glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S-transferase-pi, we found significant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P-glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase-II expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Limk1 is predominantly expressed in neural tissues and phosphorylates serine, threonine and tyrosine residues in vitro.

We have isolated the murine Limk1 gene, which is a single copy gene located at the distal end of mouse chromosome 5. Limk1 exhibits a 95% homology to the human homologue, LIMK, which contains two LIM domains and a putative protein kinase domain. Although Limk1 and LIMK contain all motifs found in catalytic kinase domains, amino acids previously described to be diagnostic of either serine/threonine- or tyrosine-kinases are not present. It is demonstrated that GST-Limk1-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro and that mutation of residue D460 within the IHRDL motif abolishes kinase activity. Northern blot showed preferential expression of a 3.5 kb message in adult spinal cord and brain. In situ hybridisation confirmed high expression levels in the nervous system, particularly in the spinal cord and the cranial nerve and dorsal root ganglia. Limk1 also contains two tandem LIM-domains. These zinc-finger like domains can mediate protein-protein interactions and have been described in nuclear and cytoskeletal proteins. The combination of LIM- and kinase domains may provide a novel route by which intracellular signalling can be integrated.

Amino Acid Sequence↗

PubMed1995

A radioactive assay for the degradation of neuropeptide Y.

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian central nervous system. Like other neuropeptides, NPY is inactivated by specialized neuropeptidases. To trace the degradation of NPY, an assay was established using biotinylated NPY. Biotinyl-NPY was radiolabeled with Na125l by the chloramine-T method and bound to a streptavidin-agarose matrix. The amount of radiolabeling was analyzed by reverse-phase HPLC. The assay was carried out with five peptidases and inhibitors to demonstrate different specific activity. Measurable amounts of radioactivity were released by treatment with endopeptidase-24.18, plasmin, and trypsin, whereas dipeptidylpeptidase IV (DPPIV) and angiotensin-converting enzyme (ACE) showed no activity in this assay. In the case of DPPIV this is due to a resistance of the assay to aminopeptidase attack. The assay is useful to study the specific degradation of NPY particularly by endopeptidases in all kinds of biological samples.

Amino Acid Sequence↗

PubMed1995

Paediatric surgical oncology. 5--Nephroblastoma. International Society of Paediatric Oncology (SIOP) Nephroblastoma Trial & Study Committee.

The favourable results from the treatment of Wilms' tumour are an example of the success of multimodal therapy in paediatric oncology. The epidemiology, methods of diagnosis, benefits of pre-operative chemotherapy, basic principles of surgery and post-operative treatment modalities are presented. The approach to the management of Wilms' tumour considered in this paper is mainly that of the International Society of Paediatric Oncology.

Chemotherapy, Adjuvant↗

PubMed1995

Mutations of p53 in Wilms' tumors.

Mutations of p53 frequently occur in a wide variety of cancers including lung, breast, gastrointestinal, brain, and hematologic malignancies. These alterations apparently contributed to development of the malignant phenotype. Wilms' tumor is one of the most common solid tumors in childhood. The frequency of p53 alterations in this tumor is unknown. We analyzed 66 Wilms' tumor samples for p53 mutations by single-stand conformational polymorphism (SSCP) following polymerase chain reaction (PCR). Samples with an abnormal SSCP pattern were reamplified and analyzed by direct sequencing method. Mutations of p53 were found in three (5%) of 66 Wilms' tumors within the coding region (exons 2-11), showing that the frequency of p53 mutations was low. Two mutations substituted amino acids residues and one encoded a stop codon. Two of the mutations were located in the mutational hotspots (exons 5 and 6); the other was in exon 10. These data suggest that p53 mutations are infrequent in the development of Wilms' tumors.

Base Sequence↗

PubMed1994

Circulating haematopoietic progenitors during treatment of renal anaemia with recombinant human erythropoietin.

The effect of recombinant human erythropoietin (rhEPO) and interleukin 3 (IL3) on circulating haematopoietic progenitors consisting mainly of immature burst-forming-units-erythrocytes (BFU-E), was investigated in ten paediatric patients treated by regular haemodialysis. During a 30-week study rhEPO treatment resulted in a rise of median haemoglobin levels from 6.7 g/dl to > 10 g/dl in all patients. Before initiating rhEPO treatment the number of circulating BFU-E in chronic renal failure patients responded to grading doses of rhEPO in vitro similar to that in control children; however, the dose-response curves were not predictive for the in vivo response to rhEPO. After an initial rise in five patients BFU-E numbers declined by week 30 of rhEPO treatment. BFU-E numbers decreased to 35% of pretreatment values. The number of granulocyte-macrophage colony forming cells (GM-CFC) also decreased during rhEPO treatment. Addition of IL3 to the culture medium containing saturating concentrations of granulocyte-macrophage colony stimulating factor did not stimulate BFU-E numbers of patients before rhEPO treatment or those of controls. However, 2 weeks after start of rhEPO treatment IL3 increased the growth of patient's BFU-E in vitro to 220% of pretreatment levels, followed by a gradual decrease of stimulation until the end of observation. These findings indicate that: (1) long-term recruitment of circulating haematopoietic progenitors during rhEPO treatment is low in children with renal anaemia; (2) rhEPO sensitivity of circulating BFU-E is not predictive for the in vivo response; (3) rhEPO treatment results in enhanced sensitivity of BFU-E to IL3.

Adolescent↗

PubMed1994

Hepatotoxicity in irradiated nephroblastoma patients during postoperative treatment according to SIOP9/GPOH.

This report describes liver toxicity in the risk group qualifying for combined postoperative irradiation and chemotherapy according to SIOP9/GPOH and diagnosed between January 1989 and June 1992 in hospitals participating in the GPOH studies (German Pediatric Oncology Hematology Group). Of 269 Wilms' tumor patients receiving postoperative treatment, 58 had abdominal irradiation (local SIOP, Stages II N+ and III standard histology [SH, n = 42]; and local Stages II and III, unfavorable histology [UH, n = 16]). Age was between 6 months and 22 years. Parallel to abdominal irradiation the patients were treated with polychemotherapy of differing combination depending on surgical stage and histology. All of them received actinomycin D (ACT D) and vincristine. However, ACT D was given according to protocol for standard histology Stage II and III in a dose of 15 micrograms/kg on 5 consecutive days and as single injection of 30 micrograms/kg in Stage IV standard and in unfavorable histology. For 37/58 children the major part (> 50%) of the liver was within the irradiation portals and 28/37 had whole liver irradiation. Doses ranged between 12 and 22.5 Gy and in 9 children parts of the liver received additional irradiation up to a total of 30 Gy. Eleven of 58 children (18%) developed hepatotoxicity and 4 of them veno-occlusive disease (VOD). Liver toxicity in irradiated patients occurred at a median of 6.5 weeks after start of postoperative treatment. The rate of toxicity was 4/14 versus 7/23 in patients receiving > 20 versus < 20 Gy to the major part of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Differential expression of leukocyte differentiation antigens in small round blue cell sarcomas.

BACKGROUND: Small round blue cell sarcomas (SRBCS) comprise a group of cytomorphologically poorly differentiated neoplasms that are characterized by different histogenesis and biologic behavior. METHODS: Twenty-seven well-characterized SRBCS were examined immunohistochemically to detect the expression of a panel of leukocyte differentiation (CD) antigens and class I (HLA-A,B,C) and class II (HLA-DR) major histocompatibility complex antigen. RESULTS: Although various cell surface antigens were detectable in SRBCS, the pan-leukocytic-histiocytic CD53 antigen was absent in the neoplastic population of all tumors studied; this finding allowed the authors to discriminate these lesions from lymphomas and leukemias. Some antigens had a differential pattern of expression in the SRBCS group, in particular in the undifferentiated tumor cell populations. In most instances, neuroblastomas (NB) and ganglioneuroblastomas (GNB) were CD9+/CD24+/CD56+ but CD40-/HLA-A,B,C-. Rhabdomyosarcomas (RMS) were CD56+ in all specimens and CD9+ in many samples; generally, they showed CD24-/CD40-/HLA-A,B,C-. Ewing sarcomas (ES) and peripheral primitive neuroectodermal tumors (pPNET) were HLA-A,B,C+/CD40+ but CD9-/CD24-/CD56- in most instances. Thus, with few exceptions, the expression of CD9 and CD56 and the simultaneous absence of HLA-A,B,C and CD40 differentiated GNB, NB, and RMS from ES and pPNET. GNB, NB, and RMS differed in regard to their CD24 expression. CONCLUSIONS: These data show that various types of SRBCS have different patterns of cell surface antigens. Therefore, these antigens are considered to be helpful in the immunophenotypic subclassification of SRBCS: The immunophenotypic similarities between ES and pPNET, however, might be an additional argument for a close relationship between these two lesions.

Antigens, CD↗

PubMed1993

Exon skipping due to a mutation in a donor splice site in the WT-1 gene is associated with Wilms' tumor and severe genital malformations.

A germline WT-1 point mutation is described in a patient with unilateral Wilms' tumor, nephritis and ambiguous external genitalia. The patient was diagnosed as a possible case of Denys Drash syndrome (DDS). Analysis of the WT-1 exons and intron borders revealed a G to C transversion in the +1 position of the splice donor consensus sequence in intron 6. Two transcripts of abnormal size were identified in tumor RNA. Sequencing of the altered WT-1 mRNA revealed that this point mutation leads to exon-skipping, resulting in transcripts either missing exon 6 or exons 5 and 6. The normally occurring alternative splicing of exon 5 in the WT-1 gene is not affected by this mutation. The reading frame is changed when either both exons 5 and 6 or exon 6 alone are missing and a stop codon follows immediately downstream in exon 7. Most mutations identified in DDS are missense mutations located in the zinc finger (ZF) region (exons 7, 8 and 9) but recently a patient with a germline mutation in exon 6 leading to premature chain termination was described. Therefore the site of the mutation in the WT-1 gene in this patient cannot exclude the possibility that he has DDS.

Base Sequence↗

PubMed1993

Chemotherapy with cytosine arabinoside in a child with Burkitt's lymphoma on maintenance hemodialysis and hemofiltration.

A case of Burkitt's lymphoma (stage IV) in an 8-year-old boy with end-stage renal failure due to hemolytic uremic syndrome is reported. The boy was treated by maintenance hemodialysis (HD) and hemofiltration (HF). During chemotherapy treatment with continuous cytosine arabinoside (Ara-C) infusion (100 mg/m2/d) for 7 days, concentrations of Ara-C and its metabolite uracil arabinoside (Ara-U) were measured in blood, dialysate, and filtrate. Ara-C levels were always below 200 ng/ml and were only qualitatively detectable in blood, dialysate, and filtrate. Ara-U levels were higher than 200 ng/ml after 18 h treatment and were measured quantitatively. Ara-U clearance during 3 h HD was 92 ml/min and the calculated mass removal 14.7 mg/3 h. In contrast, the Ara-U clearance during 3 h HF was 14 ml/min and the mass removal was 6.7 mg/3 h. Ara-C and Ara-U are eliminated by HD and HF in anuric patients. A continuous infusion of 100 mg Ara-C m2/d during HD or HF treatment did not result in a serum concentration above 200 ng/ml.

Arabinofuranosyluracil↗

PubMed1993

Chemotaxis of polymorphonuclear neutrophils (PMN) in patients suffering from recurrent infection.

PMN function was tested in patients suffering from recurrent infections. In 65 out of 240 patients lack of oxygen radical production or reduced chemotactic activity was found. In most cases the reduction was transient and associated with clinical impairments of the patients. Only a few patients had primary cellular defects. In one of those patients the expression of beta 2 integrins was reduced, while PMN of the other patients expressed beta 2 integrins normally. Thus, cellular defects other than the reduced expression of beta 2 integrins might also result in impaired chemotactic activity.

Adult↗

PubMed1992

Identification in human urine of a natural growth inhibitor for cells derived from solid paediatric tumours.

Partially purified urine of healthy human subjects contains several fractions able to inhibit the proliferation of cultured human neuroblastoma cells. One of the most active fractions was further analysed by gas chromatography-mass spectrometry and shown to contain genistein, a substance formed in the human body from precursors obtained by diet. Synthetic genistein was able to inhibit the proliferation of human neuroblastoma cells with a half-maximal effect at 5-10 mumol l-1 concentrations. Genistein displayed similar potencies in inhibiting the proliferation of cells derived from various other solid pediatric tumours. Our results suggest that genistein is a natural antineoplastic agent present in diet and that it could be useful for the therapy of paediatric tumours.

Cell Division↗

PubMed1992

[Sonography in therapy-oriented diagnosis and after-care of primary bone and soft tissue tumors].

Based on the results of 150 patients with primary tumors or the suspicion of malignant lesions of the locomotor system the perspectives and limits of the sonographic diagnosis under the therapeutic aspects of interdisciplinary oncologic cooperation is demonstrated. As the ideal adjunct to conventional roentgenograms, ultrasound is the first-line imaging procedure in the fields of primary diagnosis, follow-up, post-therapeutic care as well as tumor exclusion for methodic, patient-related and economic/logistic reasons. Its consequent application will markedly reduce the number of more invasive and expensive methods.

Adult↗