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Biomedical subjects

U Schulz

Publications and source records attributed to U Schulz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Soft tissue sarcomas after radiation treatment for breast cancer. Three case studies and review of literature.

AIMS: By means of 3 cases with infield soft tissue carcinomas after radiotherapy for breast cancer, symptoms and therapy are described. Consequences for treatment planning and patient's information before radiotherapy for breast cancer are discussed. PATIENTS: Three of 1,025 patients with breast cancer irradiated from 1984 to 1997 suffered from infield secondary soft tissue sarcomas. The latency periods were 61, 49 and 59 months. Two patients had been treated with breast-conserving therapy (computerized planning, 50 Gy to reference point, 5 times 2 Gy/week, 5-MV photons), 1 patient received a local boost dose of 15 Gy (10-MeV electrons), patient 3 radiotherapy of the thoracic wall and regional lymph nodes after mastectomy using 12-MeV electrons (thoracic wall) and 5-MV photons (lymph node areas) to 50 Gy, 5 times 2 Gy/week. No adjuvant chemotherapy was given. All sarcomas were very extensive, all patients died from local progression and/or distant failure after 17, 13 and 12 months. RESULTS: The incidence of spontaneous sarcomas of the breast is about 0.06%, after operation and radiotherapy 0.09 to 0.45%. No correlations to radiotherapy technique and no risk factors were found. Radiation dose could play a role, but there are very sparse data about this. CONCLUSIONS: Secondary soft tissue sarcomas are very rare, but familiar complications of radiotherapy. Only early diagnosis leads to a chance for cure. Because of unclear correlations to the treatment parameters and rareness of this event, in our opinion no regular information to the patient receiving radiotherapy for breast cancer is mandatory.

Aged↗
PubMed2000

Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation.

IL-10 is a potent immunosuppressant which inhibits allo-antigen-specific T cell responses. In addition, IL-10 is a strong endogenous anti-inflammatory cytokine. To investigate the role of IL-10 in the induction of acute GVHD following allogeneic bone marrow transplantation (BMT) we performed a prospective study on spontaneous IL-10 production by peripheral blood mononuclear cells (PBMNC) in 84 patients admitted for allogeneic BMT. High spontaneous IL-10 production by PBMNC at the time of admission and prior to any preparative treatment correlated with a subsequent low incidence of GVHD and transplant-related mortality (8%), as compared to patients with low or intermediate IL-10 production (50%, P < 0. 01). Our data demonstrate the prognostic significance of increased IL-10 production in BMT patients and suggest a major role of IL-10 in maintaining immunobalance in the setting of allogeneic BMT. Bone Marrow Transplantation (2000) 25, 237-241.

Adolescent↗
PubMed1999

Radiotherapy for stages I and IIA/B testicular seminoma.

Radiotherapy is generally accepted as a standard treatment for early-stage testicular seminoma. Relapse rates of 2% to 5% in clinical stage I and 10% to 20% in stage IIA/B (according to the Royal Marsden classification) can be achieved. Disease-specific survival reaches 100%. With such excellent cure rates, treatment-related side effects gain particular importance. Therefore, a prospective multicenter trial was initiated for radiotherapy of testicular seminoma with limited treatment portals and low total doses of irradiation. In clinical stage I, 483 patients were treated with 26 Gy to the para-aortic region only. In stage IIA, 42 patients and, in stage IIB, 18 patients received irradiation to the para-aortic and high iliac lymph nodes with 30 and 36 Gy, respectively. With a median time to follow-up of 55 months for stage I and 55.5 months for stage IIA/B, there were 18 (3.7%) and 4 (6.7%) cases of relapse in both treatment groups. Disease-specific survival was 99.6% in stage I and 100% in stage IIA/B. Acute toxicity was dominated by moderate gastro-intestinal side effects. No major late toxicity has been observed to date. Limited volume pure para-aortic treatment for stage I and para-aortic/high iliac irradiation for stage IIA/B with 26, 30 and 36 Gy, respectively, yields excellent cure rates with only moderate acute toxicity and is therefore recommended as standard treatment.

Adolescent↗
PubMed1999

Galectin-1, a natural ligand for the receptor-type protein tyrosine phosphatase CD45.

Galectin-1 binds preferentially to N-acetyllactosamine residues on oligosaccharides associated with several cell surface glycoconjugates. In the present work, placental galectin-1 has been identified to be a natural ligand for the receptor-type protein tyrosine phosphatase CD45. The binding of galectin-1 to CD45 was detected by affinity chromatography of NP 40 solubilized Jurkat T cell membranes on galectin-1 agarose followed by immunoblotting of the galectin-1 agarose bound fraction applying monoclonal antibodies to CD45 isoforms. The PTPase activity of the galectin-1 agarose binding membrane fraction could be inhibited by sodium orthovanadate. Preincubation of Jurkat T cell membrane preparations with galectin-1 decreased the membrane-associated PTPase activity in a concentration-dependent manner. Incubation of Jurkat cells with galectin-1 suppressed the immunoprecipitated PTPase activity of CD45. Galectin-1 stimulates the cell surface expression of phosphatidylserine an early indicator of apoptosis. In CD45+ Jurkat T cells, galectin-1 induces higher levels of phosphatidylserine when compared with CD45- Jurkat cells. These observations indicate that galectin-1-mediated ligation of CD45 is involved in the induction of apoptosis in Jurkat T cells.

Apoptosis↗
PubMed1999

gamma2-COP, a novel imprinted gene on chromosome 7q32, defines a new imprinting cluster in the human genome.

We describe a novel imprinted gene, gamma 2-COP (nonclathrincoatprotein), identified in a search for expressed sequences in human chromosome 7q32 where the paternally expressed MEST gene is located. gamma 2-COP contains 24 exons and spans >50 kb of genomic DNA. Like MEST, gamma 2-COP is ubiquitously transcribed in fetal and adult tissues. In fetal tissues, including skeletal muscle, skin, kidney, adrenal, placenta, intestine, lung, chorionic plate and amnion, gamma 2-COP is imprinted and expressed from the paternal allele. In contrast to the monoallelic expression observed in these fetal tissues, biallelic expression was evident in fetal brain and liver and in adult peripheral blood. Biallelic expression in blood is supported by the demonstration of gamma 2-COP transcripts in lymphoblastoid cell lines with maternal uniparental disomy 7. Absence of paternal gamma 2-COP transcripts during embryonic development may contribute to Silver-Russell syndrome. However, on mutation scanning the only gamma 2-COP mutation detected was maternally derived. Amino acid comparison of gamma2-COP protein revealed close relation to gamma-COP, a subunit of the coatomer complex COPI, suggesting a role of gamma2-COP in cellular vesicle traffic. The existence of distinct coatomer complexes could be the basis for the functional heterogeneity of COPI vesicles in retrograde and anterograde transport and/or in cargo selection. Together, gamma 2-COP and MEST constitute a novel imprinting cluster in the human genome that may contain other, as yet unknown, imprinted genes.

Amino Acid Sequence↗
PubMed1999

Genomic structure and comparative analysis of nine Fugu genes: conservation of synteny with human chromosome Xp22.2-p22.1.

The pufferfish Fugu rubripes has a compact 400-Mb genome that is approximately 7.5 times smaller than the human genome but contains a similar number of genes. Focusing on the distal short arm of the human X chromosome, we have studied the evolutionary conservation of gene orders in Fugu and man. Sequencing of 68 kb of Fugu genomic DNA identified nine genes in the following order: (SCML2)-STK9, XLRS1, PPEF-1, KELCH2, KELCH1, PHKA2, AP19, and U2AF1-RS2. Apart from an evolutionary inversion separating AP19 and U2AF1-RS2 from PHKA2, gene orders are identical in Fugu and man, and all nine human homologs map to the Xp22 band. All Fugu genes were found to be smaller than their human counterparts, but gene structures were mostly identical. These data suggest that genomic sequencing in Fugu is a powerful and economical strategy to predict gene orders in the human genome and to elucidate the structure of human genes.

Amino Acid Sequence↗
PubMed1998

Interaction of Mg2+ with the allosteric site of muscarinic M2 receptors.

Mg2+-ions have been suspected to attenuate the inhibitory effect of allosteric modulators on the dissociation of orthosteric ligands from muscarinic M2 receptors. It was aimed to gain more insight into the molecular events underlying the effect of Mg2+. The interaction of Mg2+ with the allosteric model compounds W84 (hexane-1,6-bis [dimethyl-3'-phthalimidopropylammonium bromide]) and Chin3/6 (hexane-1 ,6-bis[dimethyl-3'-¿4-oxo-2-phenyl-3,4-dihydro-2H-quinazolin-1-yl propylammonium bromide]) was studied in porcine heart muscarinic receptors, the primary binding site of which was occupied by the ligand [3H]N-methylscopolamine ([3H]NMS). The incubation buffer was composed of 4 mM Na2HPO4 and 1 mM KH2PO4 (pH 7.4, 23 degrees C). The retardation of [3H]NMS dissociation (control t1/2=5.6 min) induced by the allosteric test compounds was diminished by 3 mM Mg2+ to a greater extent than to be expected with regard to its contribution to the ionic strength of the buffer solution. Concentration-effect curves for the allosteric retardation of [3H]NMS dissociation by W84 (half maximal effective concentration EC0.5=24 nM in the absence of Mg2+) and by Chin3/6 (EC0.5=28 nM) were shifted by Mg2+ to the right in a parallel fashion. The curve-shift was compatible with a competitive interplay between Mg2+ and the modulators. The pKb-values as a measure of the antagonistic potency of Mg2+, however, differed depending on the modulator, i.e. pKb=3.4 with W84 and pKb=2.8 with Chin3/6. Mg2+ itself was capable of slowing the dissociation of [3H]NMS; the maximal retardation of [3H]NMS dissociation was about 3 fold, the concentration-effect relationship was compatible with a two-site model using the above-mentioned pKb-values as affinity constants. Since the equilibrium-binding of [3H]NMS remained unchanged up to a Mg2+-concentration of 3 mM, the cation appears to inhibit the association and dissociation of [3H]NMS to the same extent in this concentration range. Taken together, the findings indicate that Mg2+ may bind to the allosteric region of muscarinic M2 receptors and that more than one site is involved in this interaction. The sites of action may represent divalent cation binding sites.

Allosteric Site↗
PubMed1998

Gliomatosis cerebri: a brain tumour which is too difficult to treat?

Gliomatosis cerebri is a rare form of primary diffuse brain tumour first described by Nevin in 1938. It was originally considered to be a post-mortem diagnosis before Troost et al reported a clinically diagnosed case in 1987. However antemortem diagnosis remains difficult due to vague clinical symptoms and often non-specific findings on CT scanning. Gliomatosis cerebri has been classified by the World Health Organization as an infiltrative tumoural process, which involves at least two, and usually three, lobes of the brain. Magnetic resonance (MR) imaging shows a diffuse infiltrative process with possible mass effect but no necrosis. Histology is usually of a low grade astrocytic neoplasm which seemingly infiltrates out of proportion to the degree of anaplasia. We report two patients who presented over the past year, whose clinical and radiological features prompted a preoperative diagnosis of gliomatosis cerebri, confirmed by biopsy.

Adult↗
PubMed1997

Extended field and total central lymphatic radiotherapy in the treatment of early stage lymph node centroblastic-centrocytic lymphomas: results of a prospective multicenter study. Study Group NHL-frühe Stadien.

BACKGROUND: A prospective multicenter trial was performed to evaluate survival, patterns of relapse, and toxicity for clinically staged patients with lymph node centroblastic-centrocytic (cb/cc) lymphomas in Stages I-IIIA after large extended field irradiation (EFI) or total central lymphatic irradiation (TCLI). METHODS: Between January 1986 and August 1993, 117 adults with clinical Stage I-IIIA lymph node cb/cc lymphoma (Kiel classification) were recruited. Patients in Stages I or II with mediastinal, hilar, periaortic, iliac, or mesenteric involvement and in Stage IIIA received TCLI, whereas patients with more peripherally located cb/cc lymphomas were treated with EFI. TCLI and EFI were administered to a total dose of 26 gray (Gy) with 2 Gy per daily fraction, with the exception of the whole abdomen, which was irradiated to a total dose of 25.5 Gy with 1.5 Gy per fraction. A boost of 10 Gy with 2 Gy per fraction was administered to enlarged and involved lymph nodes at the start of radiotherapy. RESULTS: Sixty, 40, and 17 patients had Stage I, II, and limited IIIA disease (no bulk and less than 6 involved lymph node regions), respectively. Overall survival was 86% at 5 and 7 years; median follow-up was 68 months. The probabilities of relapse at any site, recurrences in lymph nodes, and in-field lymph node recurrences after TCLI were 17% in Stage I; 56%, 43%, and 40% in Stage II, respectively; and 44%, 35%, and 35% in Stage IIIA, respectively. The risk of disseminated extralymphatic relapses was 9% at 7 years. The most important adverse prognostic factor for in-field lymph node recurrences was a deviation of >20% from the assigned total radiation dose. After EFI, patients in Stage I had a significantly lower risk of recurrences in adjuvant irradiated lymph node regions than in unirradiated lymph node regions. Acute toxicity of EFI and TCLI was moderate. CONCLUSIONS: In-field lymph node recurrences remained the main risk after TCLI, and a deviation of >20% from the assigned radiation dose was the major risk factor for in-field recurrences. From these data, a total dose of 40-44 Gy in conventional fractionation for the treatment of macroscopic cb/cc lymphomas and 30 Gy for the treatment of subclinical disease is recommended. A randomized study comparing TCLI with EFI is now being organized by this group.

Adult↗
PubMed1997

Monoallelic expression of human PEG1/MEST is paralleled by parent-specific methylation in fetuses.

We have isolated the human PEG1/MEST gene and have investigated its imprinting status and parental-specific methylation. FISH mapping assigned the gene to chromosome 7q32, and homologous sequences were identified on the short arm of human chromosomes 3 and 5. Through the use of a newly identified intragenic polymorphism, expression analysis revealed that PEG1/MEST is monoallelically transcribed in all fetal tissues examined. In two informative cases, expression was shown to be confined to the paternally derived allele. In contrast to the monoallelic expression observed in fetal tissues, biallelic expression was evident in adult blood lymphocytes. Biallelic expression in blood is supported by the demonstration of PEG1/MEST transcripts in a lymphoblastoid cell line with maternal uniparental disomy 7. The human PEG1/MEST gene spans a genomic region of approximately 13 kb. Sequence analysis of the 5' region of PEG1/MEST revealed the existence of a 620-bp-long CpG island that extends from the putative promoter region into intron 1. We demonstrate that this CpG island is methylated in a parent-of-origin-specific manner. All MspI/HpaII sites were unmethylated on the active paternal allele but methylated on the inactive maternal one.

Adult↗
PubMed1996

[Quality and the profit situation in ambulatory radiotherapy].

BACKGROUND: Increasing demands of quality assurance and growing complexity of the concepts of radiotherapy planning produce increasing costs. These costs, on the other hand, cannot be got back from the paying institutions, because, in general, treatment sessions are paid in a lump sum. Using examples from everyday's practice, it will be shown, in which range levels of quality have an influence on profit. METHOD: For 4 frequent indications for curative radiotherapy: NSCLC, radiotherapy after breast-conserving operation for breast cancer, cancer of the hypopharynx and cancer of the uterine cervix, treatment plans on 3 different quality levels have been created. For each treatment step, times in minutes have been measured and costs calculated according to staff, machines, and rooms. RESULT: Rising quality levels implies, in general, lowering the profit. CONCLUSIONS: Radiotherapists have to define in their workshops, which quality level is tolerable, essential, desirable or an option for the future. The single radiotherapist, then, has to decide, on what quality level he is able to work, and which radiotherapy techniques he cannot afford to offer in general or at certain times. The professional organisations have the difficult task to fight for a level of reimbursement allowing the further evolution of our profession.

Ambulatory Care↗
PubMed1995

In-vivo investigation of material quality of bone tissue by measuring apparent phalangeal ultrasound transmission velocity.

The square of ultrasound transmission velocity in a material is related to the modulus of elasticity, which is known to be an indicator of stability in bone. The aim of our study was to use ultrasound transmission velocity to obtain information about the material properties of bone tissue, keeping other factors possibly influencing ultrasound transmission as constant as possible. Apparent phalangeal ultrasound transmission velocity (APU) measured in 54 isolated, fresh pig phalanges was shown to be independent of bone mineral density (BMD) measured by SPA. Fastest sound transmission led exclusively through cortical bone so that intertrabecular connectivity in spongious bone could not influence the result. In humans APU was measured in the mediolateral direction at the midphalanx of the middle finger. In 53 healthy subjects (15-81 years old; 27 women, 26 men), there was a decrease of APU with age (r = -0.30, p < 0.05). Further, when comparing the results of both hands intraindividually almost identical values indicated constant intraindividual architecture of bone at this location. There was no evidence for a relation of APU to physical load comparing dominant and nondominant hand and relating the results to subjectively estimated physical load. In a second group of 43 perimenopausal women (47-60 years old), APU, which again decreased with age (r = -0.33, p < 0.05), was found not to be correlated to BMD measured by SPA at the distal forearm (cortical bone).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Electrofishing from animal welfare aspects].

Through improper application of electrofishing techniques fish may be harmed severely. The injuries can range from inner bleeding to broken vertebrae. Due to these possible injuries each electrofishing procedure requires approval of the fisheries authorities. Only persons with a special license are allowed to fish with electricity. The fisheries authorities only approve electrofishing for reasons stated in the fisheries laws. If an application to fish with electricity is approved, the permission is restricted to certain persons, certain equipment units, certain stretches of water and clearly outlined goals. Damages to fish can be reduced to a minimum by the strict regulations of the fisheries authorities and by the training of the fishermen.

Animal Welfare↗
PubMed1995

[Long-term experiences with a long-acting gonadotropin releasing hormone analog in therapy of central precocious puberty: effect on body growth].

In central precocious puberty (CPP), characterised by premature but otherwise normal puberty, the early onset of the pubertal growth spurt with increased height velocity results in premature epiphyseal closure with reduced final height. We examined the growth pattern in 11 patients (9 girls and 2 boys) with CPP treated with a long-acting gonadotropin-releasing hormone analogue (GNRHa). Every 28 days 75 micrograms of the GNRHa Triptorelin (Decapeptyl CR, Fa. Ferring) per kg body weight are given intramuscularly. We observed body height, height velocity, bone maturation (dBA/dCA) and predicted adult height in these patients for up to 4 years. Before treatment body height was markedly elevated (2.5 +/- 4.4 SD above the age appropriate mean); after two years of therapy it reached the normal range. Height velocity decreased significantly within the first six months of treatment and remained subsequently low (F = 7.59; p < 0.0001). In the first year on treatment bone maturation (dBA/dCA) dropped from 1.8 +/- 0.42 to 0.7 +/ 0.27 and in the second year to its lowest value of 0.3 +/- 0.13 (F = 2.35; p < 0.05). The predicted adult height increased from 154.5 +/- 4.0 cm at the beginning of treatment to 160.3 +/- 3.9 cm at the most recent follow-up examination. The present data indicate that treatment with a long-acting GNRHa markedly affects body growth in CPP by reducing height velocity and delaying bone maturation. The predicted adult height appears to increase, consequently.

Adolescent↗
PubMed1993

Architecture in cortical bone and ultrasound transmission velocity.

The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.

Animals↗
PubMed1993

Fluorescence microscopic studies and flow cytometric measurements of lectin and hormone binding to isolated rat pancreatic acinar cells.

The binding of fluorescence-labelled lectins and a fluorescence-marked hormone to the cell surface of isolated rat pancreatic acinar cells was studied by light microscopy and flow cytometric measurements. The pancreatic acinar cells were prepared by collagenase digestion. The fluorescence of cells was studied after binding of FITC-labelled WGA or UEA I as well as of FITC-marked pancreocymin/cholecystokinin (CCK-FITC) in a fluorescence microscope or FACScan. The strong binding of lectins was inhibited by preabsorption with the specific sugars. In comparison to the lectins the binding of CCK-FITC was low. There were two populations of acinar cells with different CCK-FITC binding capacity as detected by flow cytometry. The CCK-FITC cell surface fluorescence was significantly decreased by preincubation with unmarked hormone as well as with the non-labelled lectins. The inhibition of CCK-FITC binding by lectins is discussed in respect to a possible competition of the lectins and CCK for the CCK receptor.

Animals↗
PubMed1993

Lectin binding studies with FITC-marked WGA and UEA I and flowcytometric measurements on isolated rat pancreatic acinar cells.

Lectin binding to the glycocalyx of isolated rat pancreatic acinar cells was studied by flowcytometric measurements. The pancreatic exocrine cells were prepared after collagenase digestion and cleaned in a density gradient. The fluorescence of cells was measured in a FACScan after binding of FITC marked WGA or UEA I. The binding of lectins was inhibited by preabsorption of WGA-FITC with N-acetyl-glucosamine, sialic acid or chitinous and by preabsorption of UEA-FITC with alpha-L-fucose, respectively. Furthermore, we were able to measure a decreased WGA-FITC and UEA-FITC binding after a short preincubation of isolated cells with the peptide hormone cholecystokinin and its agonists (caerulein, pentagastrin).

Animals↗