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Ulrich Schaefer

Publications and source records attributed to Ulrich Schaefer.

10 recordsLinked to original sources
PubMed2006

The plasminogen activator system modulates sympathetic nerve function.

Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.

Adrenergic Fibers↗
PubMed2005

Optimization of the TRAP assay to evaluate specificity of telomerase inhibitors.

Telomerase inhibition represents a promising approach to anticancer treatment. In order to clarify the therapeutic potential of telomerase inhibitors we examined different substances (small molecule compounds BIBR1532 and BRACO19, as well as hTR antisense oligonucleotides 2'-O-methyl RNA and PNA) in A-549, MCF-7, and Calu-3 cell lines in a cell-free TRAP assay. We demonstrated that each of the tested agents inhibited telomerase in all used cell lines and that the antisense oligonucleotides represent the most potent inhibitors. Interestingly, upon evaluating the specificity of telomerase inhibitors we found out that not all agents acted specifically against telomerase. We observed that BRACO19 and PNA had an inhibitory effect also on PCR amplification of the TSR8 oligonucleotide which is provided in the TRAP(EZE) kit as a PCR control. By modifying the experimental protocol and using a different reverse primer we were able to enhance PNA selectivity, although the PCR inhibition of the TSR8 control template by BRACO19 could not be prevented. We propose an explanation for the lack of target specificity and suggest caution when testing putative telomerase inhibitors, as it appears that some of those substances may not affect specifically telomerase or telomeric G-rich sequences and thus can lead to the misinterpretation of experimental results.

Acridines↗
PubMed2004

Mast cells: a unique source of renin.

In addition to the traditional renin-angiotensin system, a great deal of evidence favors the existence of numerous independent tissue-specific renin-angiotensin systems. We report that mast cells are an additional source of renin and constitute a unique extrarenal renin-angiotensin system. We use renin-specific antibodies to demonstrate that cardiac mast cells contain renin. Extending this observation to the human mast cell line HMC-1, we show that these mast cells also express renin. The HMC-1 renin RT-PCR product is 100% homologous to Homo sapiens renin. HMC-1 cells also contain renin protein, as demonstrated both by immunoblot and immunocytochemical analyses. Renin released from HMC-1 cells is active; furthermore, HMC-1 cells are able to synthesize renin. It is known that, in the heart, mast cells are found in the interstitium in close proximity to nerves and myocytes, which both express angiotensin II receptors. Inasmuch as myocardial interstitium contains angiotensinogen and angiotensin-converting enzyme, and because we were able to detect renin only in mast cells, we postulate that the release of renin from cardiac mast cells is the pivotal event triggering local formation of angiotensin II. Because of the ubiquity of mast cells, our results represent a unique paradigm for understanding local renin-angiotensin systems, not just in the heart, but in all tissues. Our findings provide a rationale for targeting mast cells in conjunction with renin-angiotensin system inhibitors in the management of angiotensin II-related dysfunctions.

Animals↗
PubMed2002

A long-term follow-up study after retro-orbital irradiation for Graves' ophthalmopathy.

PURPOSE: The aim of this retrospective analysis was to find out whether low-dose radiation, which is used in the treatment of Graves' ophthalmopathy, could cause radiation-induced cancer, which would in turn adversely affect the survival of the irradiated population and cause an increase in the cancer-specific death rate. METHODS AND MATERIALS: From 1963 to 1978, 250 patients received bilateral orbital irradiation for a progressive Graves' ophthalmopathy. Median age was 49 years. Overall survival and causes of death were evaluated with the help of patients still living, registration offices, medical records, referring physicians, and relatives. Survival curves were calculated with the Kaplan-Meier method. The outcome for each patient was compared with data from life tables regarding gender, age, and calendar period-specific person-years at risk. In addition, treatment outcome for living patients was evaluated with a questionnaire. RESULTS: After a median follow-up of 31 years, 102 patients are still alive, 123 patients have died, and 25 patients have been lost to follow-up. The 10-year, 20-year, and 30-year survival rates were 89%, 68%, and 49%, compared with the age-adapted survival rate of the normal population of 92%, 76%, and 52%. Evaluation of cancer-specific survival was possible in 166 cases. The 10-year, 20-year, and 30-year cancer-specific survival rates were 98%, 92%, and 88%, compared with 97%, 93%, and 87% in the normal population. Treatment response was evaluable in 94 cases. A complete response was reported in 41 patients, a partial response in 39 patients, and no change in 14 patients. CONCLUSIONS: No significant evidence of radiation-induced cancer death was seen in this small cohort of patients treated with radiotherapy for Graves' ophthalmopathy. The long-term treatment results seem to be satisfactory. Studies with greater numbers of patients are necessary to examine the risks and benefits more precisely.

Cause of Death↗
PubMed2002

Systemic mast cell disease (SMCD) and bone pain. A case treated with radiotherapy.

BACKGROUND: Systemic mast cell disease (SMCD) is a rare disease characterized by a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells. SMCD preferentially involves the skin, spleen, liver, lymph nodes and the bone marrow. The cause of SMCD is unknown. Bony pain, caused by mast cell infiltration of the marrow cavity, is present in up to 28% of cases and is frequently chronic and difficult to palliate with medical therapy. CASE REPORT: We report one case of refractory bone pain in a 54-year-old female Caucasian patient with advanced SMCD and associated bony involvement, which was treated with radiotherapy for pain palliation. Between 1995 and 1998, the patient was irradiated at four different locations: 1) right shoulder and proximal right humerus, 2) both hands, 3) both knees, 4) left humerus with a total dose of 40 Gy in 2.0 or 2.5 Gy daily fractions. RESULTS: Different results of pain palliation were achieved. In one location the pain was reduced for 55 months until her death due to disease progression, whereas in two other locations a pain control was maintained for 3 and 6 months after radiotherapy. In one location, no pain reduction was achieved. Severe side effects were not observed. CONCLUSION: Palliative radiotherapy has a role in the control of severe intractable bone pain in patients with advanced SMCD, though in some cases the effect may be short or incomplete. The observed palliation of pain can even differ in the same patient.

Bone and Bones↗
PubMed2002

Split liver transplantation and risk to the adult recipient: analysis using matched pairs.

BACKGROUND: The technique of liver splitting is an effective way of increasing the donor pool and reducing pediatric waiting list mortality. But the procedure is still not fully accepted because of concerns that it may cause complications in adult recipients. STUDY DESIGN: Fifty-nine adult recipients of primary extended right split liver transplantations (SLTs) were matched to recipients of whole liver transplantations (WLTs) according to the following criteria: 1) United Network for Organ Sharing (UNOS) status, 2) donor age, 3) recipient age, 4) total cold ischemic time, 5) indication for liver transplantation, 6) Child-Pugh class, and 7) year of transplantation. A WLT-recipient match was identified in 40 adult recipients of primary SLT. RESULTS: Fifteen percent of the recipients in our study were highly urgent cases (UNOS 1), and 85% were UNOS status 3-4. The 3- and 12-month patient survival rates after SLT and WLT were 82.5% and 77.1%, and 92.5% and 87.5%, respectively (log rank p = 0.358). The 3- and 12-month graft survival rates showed no significant difference in either group (80% and 74% in SLT and 87.5% and 77.4% in WLT [log rank p = 0.887]). The rates of primary nonfunction, primary poor function, biliary and vascular complications, intra- and postoperative blood transfusion, and intensive care stay were comparable for SLT and WLT. CONCLUSIONS: SLT, using the extended right hepatic lobe, does not notably differ from WLT with regard to initial graft function, postoperative complications, or patient and graft survival. Based on this, the liver can be considered a paired organ, and mandatory splitting of good-quality livers can be recommended.

Adolescent↗
PubMedDate not supplied

Intraoperative radiation therapy (IORT) in primary locally advanced and recurrent carcinoma of the rectum at a "non-dedicated" facility.

BACKGROUND: Primary locally advanced and recurrent colorectal cancer still present a significant clinical challenge. Local failure rates are high in both situations. Promising results have been reported by combined radiochemotherapy, extensive surgery and intraoperative radiation therapy (IORT). Our aim was to perform IORT at a "non-dedicated" facility to improve the local tumour control rate without increasing the complication rate. MATERIALS AND METHODS: From February 1997 to April 2001, 19 patients with recurrent and 4 patients with primary locally advanced colorectal cancer underwent surgery and IORT. The histology was adenocarcinoma in all cases. A complete removal of the tumour was possible in 11 patients, while an incomplete resection was achieved in 12 cases. IORT doses ranged from 10-20 Gy and electron energies from 6-14 MeV were used. Fourteen patients had pre- or postoperative external beam radiochemotherapy. RESULTS: After a median follow-up of 27 months, 18 patients (78%) are alive. Five of these patients have a progressive disease. Five patients (22%) died in progressive disease. The amount of residual cancer remaining after surgery is an important factor regarding treatment outcome. Complications were observed in 8 patients (35%). These complications were severe only in 4 patients (17%). Fifteen patients (65%) have had no complications at all. No perioperative or postoperative deaths were seen. CONCLUSION: IORT combined with radical surgery, external beam radiotherapy and systemic chemotherapy is feasible at a "non-dedicated" facility without increasing the postoperative complications. A complete resection is the most important factor for a favourable outcome.

Adenocarcinoma↗
PubMedDate not supplied

Selenium influences the radiation sensitivity of C6 rat glioma cells.

BACKGROUND: A radioprotective effect of low selenium doses on normal tissue and a possible radiosensitization of tumor cells at higher concentrations have been previously suggested. However, systematic experimental and clinical data are scarce. MATERIALS AND METHODS: C6 cells were cultured for 14 days at different selenite concentrations (0 microM, 2 microM, 3 microM and 3.6 microM) and irradiated with 0 Gy to 20 Gy. Plating efficiency and survival were determined using the colony assay. RESULTS: The overall radiosensitivity was low (D0,control=6.1 Gy). Irradiated cells exposed to increasing selenite concentrations showed a lower plating efficiency and, for doses > 2 Gy, a lower survival than the control. For Se concentrations of 0 microM, 2 microM and 3 microM, respectively, SF2 amounted to 0.72, 0.48 and 0.46, and SF5 to 0.37, 0.25 and 0.12. Student's t-test yielded a significant difference between the 0 microM and 3 microM curves at 5 Gy (p=0.02) and 10 Gy (p=0.009). CONCLUSION: Our experiments suggest a radiosensitizing effect of selenite in glioma cells at concentrations of 2-3 microM.

Animals↗
PubMedDate not supplied

No predictive value of beta-hCG in patients with stage I seminoma--results of a long-term follow-up study after adjuvant radiotherapy.

BACKGROUND: Radical inguinal orchiectomy followed by adjuvant para-aortic radiotherapy has been the standard treatment in stage I seminoma. We have reviewed our experience with reduced total doses (less than 26 Gy) in stage I seminoma to investigate if patients with an elevated beta-human chorionic gonadotropin (beta-hCG) level before orchiectomy possibly require higher total doses of adjuvant radiotherapy (RT). PATIENTS AND METHODS: Two hundred and sixty-seven consecutive patients, with newly diagnosed pure seminoma of the testis, were treated with adjuvant RT between 1992 and 2000. All patients had stage I disease. Serum AFP and beta-hCG levels were analyzed prior to and after orchiectomy in case of an elevated beta-hCG level. The measurements were repeated after RT in routine follow-up at regular intervals. Serum beta-hCG was considered as elevated if the values exceeded the normal range (up to 5 U/L). A median total dose of 25.2 Gy (range, 19.8 to 26.0 Gy) was applied to the para-aortic region. RESULTS: Fourteen patients were excluded from this analysis because beta-hCG measurement was not available. Nineteen of the remaining 253 patients (7.5%) had an elevated serum beta-hCG, which returned to normal post-operatively by the start of adjuvant radiotherapy. Median serum beta-hCG level before orchiectomy was 27.7 U/L (range, 5.1 to 420 U/L) in the group of patients with initial elevation of serum beta-hCG. This did not correlate with tumor size or rete testis invasion. After a median follow-up of 6.1 years (range, 3.0 to 11.2 years), 11 out of 267 (4.1%) patients had developed lymph node recurrence, resulting in an actuarial 5-year relapse-free survival of 96%. Median time to relapse was 19 months (range, 11 to 47 months) after RT. Only one relapsing patient initially had an elevated serum beta-hCG level of 34.1 U/L. This patient had nodal relapse within the mediastinum without renewed elevation of the serum beta-hCG level. CONCLUSION: An elevated pre-treatment beta-hCG level appears to have neither importance nor a predictive value in stage I seminoma. Therefore, we recommend the current adjuvant standard treatment without any modification for all beta-hCG-positive stage I seminoma.

Adult↗