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71.
Volker B. Fiedler Sybylle Buchheim Helmut Göbel Rolf-Eberhard Nitz 《Naunyn-Schmiedeberg's archives of pharmacology》1982,321(4):314-320
Summary The effects of i.v. molsidomine and dopamine infusion on mean haemodynamic changes, myocardial oxygen consumption (pressure-rate-product), and ultimate infarct size were studied in pentobarbital-anaesthetized, open-chest dogs and compared to those occurring in dogs receiving saline infusion. Either agent was administered in a separate setting. Haemodynamic variables and oxygen consumption were determined during a 6-h period after ligation of the left anterior descending coronary artery and collected at 1-h intervals. Infarct size was determined by post-mortem nitroblue tetrazolium stain of intracellular lactic dehydrogenase enzymes. Coronary artery ligation during saline infusion (n=8) resulted in decreased blood pressure and cardiac output, whereas heart rate, systemic peripheral resistance, end-diastolic filling pressure and myocardial oxygen consumption increased. Infarct size amounted to 24.2±3.2% (i. e., 23.8±3.1 g) of left ventricular mass. Infusion of 1.4 g/kg/min molsidomine (n=8) produced significant fall of blood pressure, cardiac output, filling pressure and oxygen consumption while heart rate and peripheral resistance were unaffected. The infarct volume was reduced to 49% (P<0.01) of that observed in saline controls. The administration of 3 g/kg/min dopamine (n=8) elevated blood pressure and cardiac output initially with a subsequent reduction of either parameter. Arteriolar vascular resistance and oxygen consumption increased but filling pressure remained unchanged. Infarct size was not different from saline controls. Infusion of 6 g/kg/min dopamine, however, significantly increased blood pressure, heart rate, and peripheral resistance. Cardiac output and filling pressure fell and myocardial oxygen consumption rose. The histochemically measured final infarct was reduced to 13.5±1.8% of left ventricle (i. e., 16.2±2.2 g, P<0.05 vs saline control), but the hearts were edematous and haemorrhagic. Therapy with molsidomine appears promising in the treatment of clinical myocardial infarction with haemodynamic sequellae. The safe use of therapy with higher dopamine doses in patients with acute myocardial infarction, however, awaits further investigation.Part of the dopamine experiments were done at Bayer AG, Institut für Pharmakologie 相似文献
72.
Pignatelli Brigitte; Bereziat Jean-Claude; Descotes Gerard; Bartsch Helmut 《Carcinogenesis》1982,3(9):1045-1049
Measurements were made of the effects of phenolic compounds,some of which are present in the human diet, on the nitrosationof proline by nitrite to give N-nitrosoproline (NPRO). In vitro,resorcinol, catechin, p-nitrosophenol and phenol were catalystsand chlorogenic acid an inhibitor; guaiacol showed a marginalcatalytic effect. Both the catalytic and the inhibiting effectswere dependent on pH and on the concentration of phenolic compounds;catalysis by resorcinol and catechin was increased at optimalratios of [nitrite]: [phenolic compound]. Endogenous nitrosationwas examined in vivo by co-administration of nitrite, prolineand a phenolic compound to rats and by monitoring the amountof NPRO excreted in the urine. Under similar experimental conditions,the catalytic effects observed in vivo decreased in the sameorder as those observed in vitro: resorcinol > p-nitrosophenol> catechin > phenol guaiacol; chlorogenic acid acted asan inhibitor. Catalysis and inhibition of N-nitrosation in ratsin vivo appears to occur via mechanisms similar to those invitro, although the effects in vivo were smaller. The implicationsof our findings for the endogenous formation of N-nitroso compoundsand for variations in exposure due to different dietary constituentsin humans are discussed. 相似文献
73.
Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very limited. Only a few specific medical therapies
for bladder disorders have therefore been established. The objective of this study was to develop a model for videomicroscopy
of bladder SMC contractions. Cells were isolated from human cystoprostatectomy specimens and cultured in a modified EMEM medium.
These cells were identified as SMCs by means of immunohistochemistry. For videomicroscopy, the culture flasks were coated
with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell culture microscope with a
time-lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in concentrations ranging from 100 μM to
10 mM, was applied. The percentage of contracting cells within the observation field was evaluated for quantitative analysis.
In control experiments without contractile stimulant 6% of the cells were observed to contract. Stimulation with acetylcholine
induced a significant dose-dependent increase to 47% in contracting cells. These results demonstrated that videomicroscopy
is an appropriate tool to investigate the contraction mechanisms of bladder SMCs. This model offers the possibility of studying
drug effects on the human detrusor in vitro.
Received: 16 September 1999 / Accepted: 1 May 2000 相似文献
74.
Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene.
Dorota Butkiewicz Odilia Popanda Angela Risch Lutz Edler Hendrik Dienemann Volker Schulz Klaus Kayser Peter Drings Helmut Bartsch Peter Schmezer 《Cancer epidemiology, biomarkers & prevention》2004,13(12):2242-2246
Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (-4) G-to-A polymorphism was identified previously in the 5' untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking <20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined. 相似文献
75.
Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. 总被引:4,自引:0,他引:4
Leo Kager Andreas Zoubek Ulrike P?tschger Ulrike Kastner Silke Flege Beate Kempf-Bielack Detlev Branscheid Rainer Kotz Mechthild Salzer-Kuntschik Winfried Winkelmann Gernot Jundt Hartmut Kabisch Peter Reichardt Heribert Jürgens Helmut Gadner Stefan S Bielack 《Journal of clinical oncology》2003,21(10):2011-2018
PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma. 相似文献
76.
Torsten Haferlach Claudia Schoch Helmut L?ffler Winfried Gassmann Wolfgang Kern Susanne Schnittger Christa Fonatsch Wolf-Dieter Ludwig Christian Wuchter Brigitte Schlegelberger Peter Staib Albrecht Reichle Uschi Kubica Hartmut Eimermacher Leopold Balleisen Andreas Grüneisen Detlef Haase Carlo Aul Jochen Karow Eva Lengfelder Bernhard W?rmann Achim Heinecke Maria Cristina Sauerland Thomas Büchner Wolfgang Hiddemann 《Journal of clinical oncology》2003,21(2):256-265
PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account. 相似文献
77.
Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. 总被引:27,自引:0,他引:27
Donghui Li Jijiang Zhu Pervez F Firozi James L Abbruzzese Douglas B Evans Karen Cleary Helmut Friess Subrata Sen 《Clinical cancer research》2003,9(3):991-997
PURPOSE: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis. 相似文献
78.
79.
Martin Ganssauge Helmut Wilhelm Karl-Ulrich Bartz-Schmidt Sabine Aisenbrey 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2009,247(12):1707-1710
Background
To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin®).Methods
Interventional case report with an 18-month follow-up.Results
A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin®) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors.Discussion
Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin®) in the treatment of retinal vascular diseases.80.