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U Krause

Publications and source records attributed to U Krause.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Association between elevated serum VEGF and polarographically measured tumor hypoxia in head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between VEGF concentration in serum (sVEGF) and polarographically measured tumor oxygenation in patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: In 56 patients with SCCHN we estimated the classical tumor parameters, the sVEGF concentration (immunoassay) and the tumor oxygenation (Eppendorf pO2 histograph). The platelet count and the tumor volume were evaluated simultaneously. RESULTS: In a unifactorial analysis the total volume (132 cm3 vs. 38 cm3), the hypoxic subvolume (HSV = total volume multiplied with the relative frequency of values < or = 5 mm Hg/63 cm3 vs. 10 cm3) and the platelet count (380 10(9)/l vs. 271 10(9)/l) were significantly higher in the patient group with a sVEGF level > 707 pg/ml compared to the group with a sVEGF below this threshold. The multifactorial analysis confirmed significant effects for the hypoxic subvolume and the platelet count. Regarding hypoxic subvolume and sVEGF as continuous parameters a significantly positive correlation was found. This correlation remained somewhat weaker but significant after inclusion of the platelet count as covariate. CONCLUSION: On base of our data a clinical association between elevated sVEGF and polarographically measured tumor hypoxia could be confirmed. This was possible considering not only the relative grade of hypoxia but also the absolute amount of hypoxic regions. The VEGF released from platelets during blood clotting influences the sVEGF level essentially, however, the hypoxia effect was not completely deleted. Due to the platelet effect an estimation of sVEGF is not able to substitute polarographical measurement of tumor pO2. Therefore in an ongoing study we investigate whether VEGF values estimated in plasma are better correlated with the polarographically measured tumor pO2 than serum VEGF levels.

Adult↗
PubMed2000

Rapid identification of all known retroviral reverse transcriptase sequences with a novel versatile detection assay.

We have developed a highly sensitive, universal assay that allows detection as well as identification of all known retroviral reverse transcriptase (RT)-related nucleic acids in a biological sample by a single two-step experiment. The assay combines polymerase chain reaction (PCR) and reverse dot-blot hybridization (RDBH), using an array of immobilized synthetic retrovirus-specific oligonucleotides and two sets of mixed oligo primers (MOPs). These primers were derived from highly conserved motifs found in all known reverse transcriptase genes. The PCR/RDBH assay was used for qualitative analyses of human endogenous retrovirus (HERV) transcription in peripheral blood mononuclear cells (PBMCs) and in particles released by the human mammary carcinoma-derived cell line T47D. Sensitivity was further demonstrated by detection of down to 10 copies of pig endogenous retrovirus (PERV) DNA in human cDNA samples. Therefore, this assay is particularly useful for the identification of retroviral sequences in xenografts as well as in recipients of xenografted tissues and organs. Moreover, it is a valuable tool to detect retroviral transcripts and particles in cell cultures used for production of therapeutic polypeptides. The assay is further suitable for monitoring vector preparation used in human gene therapy to exclude transfer of copackaged endogenous retroviruses into target cells.

Animals↗
PubMed2000

Partial purification and characterization of a wortmannin-sensitive and insulin-stimulated protein kinase that activates heart 6-phosphofructo-2-kinase.

A wortmannin-sensitive and insulin-stimulated protein kinase (WISK), which phosphorylates and activates cardiac 6-phosphofructo-2-kinase (PFK-2), was partially purified from perfused rat hearts. Immunoblotting showed that WISK was devoid of protein kinase B (PKB), serum- and glucocorticoid-regulated protein kinase and protein kinase Czeta (PKCzeta). Comparison of the inhibition of WISK, PKCalpha and PKCzeta by different protein kinase inhibitors suggested that WISK was not a member of the PKC family. In addition, WISK contained no detectable phosphoinositide-dependent protein kinase-1 (PDK1) activity. WISK phosphorylated recombinant heart PFK-2 in a time-dependent manner to the extent of 0.4 mol of phosphate incorporated/mol of enzyme subunit, and increased the V(max) of PFK-2 twofold, without affecting the K(m) for fructose 6-phosphate. WISK phosphorylated Ser-466 to a greater extent than Ser-483 in recombinant heart PFK-2, and both sites were demonstrated to be phosphorylated to the same extent by PKB. Gel filtration and in-gel kinase analysis indicated that WISK was a monomer with a M(r) of 56500. Treatment of WISK with protein phosphatase 2A (PP2A) catalytic subunits reversed the effect of insulin, suggesting the involvement of an upstream activating kinase. Indeed, PDK1 was able to partially reactivate the PP2A-treated WISK and this reactivation was not enhanced by PtdIns(3,4,5)P(3)-containing vesicles. Moreover, a single 57000-M(r) band was labelled on incubation of the dephosphorylated WISK preparation with PDK1 and [gamma-(32)P]ATP. These findings provide evidence for the existence of a new protein kinase in the insulin signalling pathway, probably downstream of PDK1.

Androstadienes↗
PubMed2000

Deep venous thrombosis and consecutive pulmonary embolism as the first sign of an ovarian cancer: MR angiography using an intravascular contrast agent (CLARISCAN).

We describe a case of progressive deep venous thrombosis and chest pain studied by contrast-enhanced magnetic resonance (MR) angiography with the new intravascular contrast medium CLARISCAN (NC100150 Injection). Combined MR venography and angiography demonstrated pelvic vein thrombosis and consecutive pulmonary embolism caused by a large abdominal tumor, diagnosed as an ovarian cancer after surgery. The potential role of an intravascular contrast medium for studying the vascular system in multiple regions of the body within a single examination without the need for bolus timing is discussed. J. Magn. Reson. Imaging 2000;12:497-500.

Clinical Trials, Phase II as Topic↗
PubMed2000

[No association between p53 overexpression and polarographically measured tumor oxygenation in patients with head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between the polarographically measured tumor oxygenation and the p53 status in patients with squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: In 99 patients with mostly advanced, histologically proven squamous cell carcinoma of the head and neck we estimated the classical tumor parameters (TNM stage, histological grading) the immunohistochemical p53-overexpression (DO-7) and the tumor oxygenation status (Eppendorf pO2 Histograph). The tumor volume and the hemoglobin concentration were evaluated simultaneously. RESULTS: No statistically significant difference could be detected between immunohistological p53-positive (p53 > or = 10% stained cells) and p53-negative tumors (p53 < 10% stained cells) regarding both the median pO2 and the relative frequency of values < or = 5 mm Hg. Moreover, no statistically relevant differences could be seen between both p53-groups considering the hemoglobin concentration, the TNM stage, the histological grading and the tumor volume. CONCLUSION: Our data imply that there is no association between p53-overexpression and tumor hypoxia in head and neck carcinomas. However, this is not necessarily in contradiction to experimental or clinical data that confirmed a relationship between hypoxia and p53-mediated increased malignancy of tumor cells in other tumor entities. The comparable oxygenation status of p53-positive and p53-negative tumors in our study is associated with an analogous clinical tumor aggressiveness of both groups. That could be caused by a hypoxia related but p53-independent selection of tumor cells with a more malignant phenotype in head and neck carcinomas. However, further research is needed to prove this possible relationship.

Adult↗
PubMed2000

Asymptomatic aneurysm of the proximal right subclavian artery: a rare ultrasound diagnosis.

True aneurysms of otherwise normal subclavian arteries are uncommon peripheral vascular anomalies. Most patients with subclavian artery aneurysms are symptomatic by presenting neurologic signs. We report a young woman who had an asymptomatic true aneurysm of the right subclavian artery assumed to be of congenital origin. This case is unique in that the aneurysm was in the extremely rare anatomic location of the right supraclavicular fossa between the origins of the right subclavian artery and the vertebral artery. Aneurysms of the right subclavian artery may represent a potential pitfall in conventional gray-scale ultrasound of the neck particularly the supraclavicular fossa. Differential diagnosis includes cervical cyst, pharyngo-esophageal diverticulum, vascular anomalies, struma, enlarged lymph node, as well benign or malignant neoplasms. Color duplex ultrasound should be performed as the method of choice for further analysis of suspected aneurysms. In this report the role of B-mode ultrasound and color duplex ultrasound is discussed in relation to digital subtraction- and MR angiography in confirmation of the diagnosis.

Adult↗
PubMed2000

Constitutive macropinocytosis in oncogene-transformed fibroblasts depends on sequential permanent activation of phosphoinositide 3-kinase and phospholipase C.

Macropinocytosis results from the closure of lamellipodia generated by membrane ruffling, thereby reflecting cortical actin dynamics. Both transformation of Rat-1 fibroblasts by v-Src or K-Ras and stable transfection for expression of dominant-positive, wild-type phosphoinositide 3-kinase (PI3K) regulatory subunit p85 alpha constitutively led to stress fiber disruption, cortical actin recruitment, extensive ruffling, and macropinosome formation, as measured by a selective acceleration of fluid-phase endocytosis. These alterations closely correlated with activation of PI3K and phosphatidylinositol-specific phospholipase C (PI-PLC), as assayed by 3-phosphoinositide synthesis in situ and in vitro and inositol 1, 4,5 trisphosphate steady-state levels, respectively; they were abolished by stable transfection of v-Src-transformed cells for dominant-negative truncated p85 alpha expression and by pharmacological inhibitors of PI3K and PI-PLC, indicating a requirement for both enzymes. Whereas PI3K activation resisted PI-PLC inhibition, PI-PLC activation was abolished by a PI3K inhibitor and dominant-negative transfection, thus placing PI-PLC downstream of PI3K. Together, these data suggest that permanent sequential activation of both PI3K and PI-PLC is necessary for the dramatic reorganization of the actin cytoskeleton in oncogene-transformed fibroblasts, resulting in constitutive ruffling and macropinocytosis.

Animals↗
PubMed1999

The GSI Cancer Therapy Project.

At the Heavy Ion Research Institute GSI in Darmstadt an experimental cancer treatment program with a five years duration has been developed. A new method for cancer treatment with ions is applied, using rasterscan method in addition to an active pulse to pulse variation of ion beam properties, including the energy, intensity and focusing. An overview of this Cancer Therapy Project is presented, that covers both accelerator aspects to provide the required beam variations within a short time and the installations at the treatment place for rasterscan control. In addition to a description of the technical design (control-hard- and software) experimental results will be shown, containing the achieved beam properties and measurements of rasterscan performance.

Academies and Institutes↗
PubMed1999

[Solitary fibrous tumors of the pleura].

Solitary fibrous tumors of the pleura (SFTP) are very rare neoplasms. The majority of these tumors are benign, but about 10-20 % fulfill the criteria of malignancy. The clinical presentation varies according to the size and intrathoracic localization. In early stages, often asymptomatic, the tumors may grow to an enormous size and then cause symptoms such as cough, chest pain and dyspnea, but also paraneoplastic syndromes such as hypoglycemia or digital clubbing. Between 1981 and June 1998 we treated in our institution 16 SFTP in 14 patients (4 M, 10 F, average age at first operation 58 years). Eight patients showed symptoms, whereas in the other cases the tumors were found on routine chest X-rays. The usually pedunculated SFTP were completely resected without complications. Two patients developed malignant recurrences, which infiltrated the right upper lung lobe and the diaphragm respectively. In these cases the tumor was resected together with the adjacent structures. Since late recurrences are more often malignant than primary SFTPs long-term follow-up is mandatory even in benign lesions.

Adult↗
PubMed1999

[Unusual intra-extracranial extension of meningioma of the lateral skull base].

Extracranial meningiomas are rare tumors of the lateral skull base. A 37-year-old woman presented with tinnitus und progressive hearing loss of her right ear. A painful mass lesion was also palpable in her mandibular angle. CT and MRI scans revealed an intracranial mass with extension to the lateral skull base. These findings suggested the occurrence of a paraganglioma or meningioma. In a two-stage surgical procedure tumor was extirpated without functional impairment to the patient. Histology of the excised lesion demonstrated an endotheliomatous meningioma. Since an extracranial meningioma can present as a mass lesion of the lateral skull base, CT and MRI scans are essential in preoperative surgical planning.

Adult↗
PubMed1998

A 2-week pretreatment with 13-cis-retinoic acid + interferon-alpha-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers.

BACKGROUND: We have evaluated the tumor tissue pO2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-alpha-2a prior to and during radiotherapy. PATIENTS AND METHODS: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-alpha-2a (IFN-alpha-2a) as part of a phase-II protocol. cRA/IFN-alpha-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6 x 10(6) IU IFN-alpha-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-alpha-2a treatment was continued with 50% of the daily doses. Tumor tissue pO2-measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO2-histograph. RESULTS: In 11 out of the 22 patients, pO2-measurements were performed prior to the cRA/IFN-induction therapy. The median pO2 of these untreated tumors was 17.7 +/- 16.3 mm Hg. The relative frequency of hypoxic readings with pO2-values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3 +/- 21.0%). After the 2-week induction period with cRA/IFN, the median pO2 had increased from 17.7 +/- 16.3 mm Hg to 27.6 +/- 19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO2 of 10 mm Hg or less), the median pO2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO2 increased from 6.3 +/- 2.7 mm Hg to 27.0 +/- 5.6 mm Hg (p = 0.004, t-test for paired samples). The frequency of hypoxic readings (pO2-values < 5 mm Hg) decreased from 44.7 +/- 17.1% to 2.0 +/- 2.5% (p = 0.012, t-test for paired samples). There was, however, no obvious volume reduction after 14 weeks of cRA/IFN on clinical examination. A complete clinical remission of the local tumor was observed in 19/22 patients after radiotherapy and additional cRA/IFN-alpha-2a-treatment. In primarily hypoxic tumors (with a median pO2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. CONCLUSIONS: Pretreatment with cRA/IFN improves oxygenation of primarily hypoxic cervical cancers. The mechanisms of action remain unclear and further investigation of the combination regimen is recommended.

Aged↗
PubMed1998

Implantable vascular access systems: experience in 1500 patients with totally implanted central venous port systems.

Totally implantable venous access systems are widely used, but large-scale studies evaluating these systems are lacking. In this study 1500 patients (719 male, 781 female) with an average age of 49 years (15-86 years) were fitted with subcutaneously implanted venous access systems, in most cases for long-term chemotherapy. All patients were observed until removal of the system, death, or the end of treatment. A retrospective analysis showed an average catheter life of 284 patient-days. A total of 1308 (87%) of the patients had no implant-related complications. Catheter infections occurred in 3.2% of the patients and catheter thromboses in 2.5%. Rarer complications, such as catheter malfunction, migration of the catheter, skin necrosis, catheter fracture, catheter disconnection, and pneumothorax, occurred in another 4.3% of the patients. The complications led to explantation of 178 access systems (11.9%). There was a significant difference (p < 0.05) between the low rate of infections and other complications in the group of patients with solid tumors (2% and 4%, respectively) and the rate in patients with hematologic diseases (6% and 8%, respectively). This study confirms the safety and convenience of using totally implantable venous access systems in patients on long-term chemotherapy.

Adolescent↗
PubMed1998

Prevention of deep venous thrombosis associated with superficial thrombophlebitis of the leg by early saphenous vein ligation.

BACKGROUND: Thrombophlebitis of the superficial veins of the leg used to be regarded as a mild and uncomplicated disease, particularly in German speaking countries. PATIENTS AND METHODS: In a retrospective clinical study from 6/91 until 12/96 we followed the progress of all patients (n = 398) with thrombophlebitis of the vena saphena magna or parva. Parameters of interest were: the incidence of concomitant deep vein thrombosis and subsequent pulmonary embolism. All patients underwent colour duplex scanning, most of them repeatedly. In cases of proven ascending superficial thrombosis, or involvement of the saphenofemoral junction, proximal saphenous vein ligation was performed (n = 56, 49 vena saphena magna and 7 vena saphena parva). Among these groups, there were 10 patients with malignant disease (18%), ten with a history of thrombosis (18%), another five comprised diabetes, recent major surgery and organ transplantation. RESULTS: In 56 operations we found free-floating thrombi 6x (11%), 19x the sapheno-femoral junction was involved (33%), 24x the saphenous vein close to the junction (43%). Three patients develop deep vein thrombosis, despite surgery (0.75% of all and 5% of the operated cases). 2 patients suffered from (non-lethal) pulmonary embolism (0.5% and 3.5%, respectively). One embolism occurred before vein ligation. Perioperative morbidity amounted to 8.5% (superficial wound infection, hematoma). CONCLUSION: Venous ligation is probably effective in reducing the rate of fatal pulmonary embolism.

Adult↗
PubMed1998

[Results of selective goiter resection in functional autonomy].

In the period from 1989 to 1994 a surgical treatment of toxic nodular goiter was performed in 145 patients. An unifocal autonomous adenoma occurred in 69 cases, a multifocal disease 76 times. The operative strategy consisted in a bilateral resection 105 times, and unilateral resection 29 times. An excision of a single node was carried out in ten cases. In one operation a hemithyroidectomy on one side and a subtotal resection of the other lobe was done. In May 1996 an interrogation about the current thyroid function was performed. In 105 (72.4%) patients a re-evaluation was possible. Concerning the postoperative therapy for prevention of recurrent hyperthyroidism or goiter growth, 84 patients (80%) had been treated with thyroxin and/or iodine. Under this therapy, after a mean period of 36 months 94 patients (89.5%) were clinically euthyroid. Nine patients (8.6%) were hypothyroid. Two patients developed a recurrent hyperthyroidism. Both of them belonged to the group of patients with multifocal autonomies, and both had been treated with thyroxin postoperatively. In one case, recurrent goiter growth occurred that did not need a therapeutic intervention. This patient as well had been treated for a multinodular goiter originally. She had not been taking a specific medication postoperatively. We conclude that a functional resection of autonomic tissue in nodular goiters is efficient in controlling the thyroid metabolism. A medical prophylaxis was not able to prevent recurrent hyperthyroidism in two cases.

Female↗
PubMed1997

Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle.

GENBANK/dy examines the mechanisms of glucocorticoid-induced insulin resistance in rat soleus muscle. Glucocorticoid excess was induced by administration of dexamethasone to rats for 5 days. Dexamethasone decreased the sensitivity of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation, glycogen synthesis and glucose oxidation to insulin. The total content of GLUT4 glucose transporters was not decreased by dexamethasone; however, the increase in these transporters in the plasma membrane in response to insulin (100 m-units/litre) was lessened. In contrast, the sensitivity of lactate formation to insulin was normal. The content of 2-deoxyglucose in the dexamethasone-treated muscle was decreased at 100 m-units/litre insulin, while the contents of glucose 6-phosphate and fructose 2,6-bisphosphate were normal at all concentrations of insulin studied. The maximal activity of hexokinase in the soleus muscle was not affected by dexamethasone; however, inhibition of this enzyme by glucose 6-phosphate was decreased. These results suggest the following. (1) Glucocorticoid excess causes insulin resistance in skeletal muscle by directly inhibiting the translocation of the GLUT4 glucose transporters to the plasma membrane in response to insulin; since the activity of hexokinase is not affected, the changes in the sensitivity of glucose phosphorylation to insulin seen under these conditions are secondary to those in glucose transport. (2) The sensitivity of glycogen synthesis and glucose oxidation to insulin is decreased, but that of glycolysis is not affected: a redistribution of glucose away from the pathway of glycogen synthesis and glucose oxidation could maintain a normal rate of lactate formation although the rate of glucose transport is decreased.

3-O-Methylglucose↗
PubMed1997

The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes.

Recent studies indicate that phosphatidylinositol 3-kinase is essential in the regulation of many processes dependent on membrane flow. Autophagy is a complex pathway in which cell material, including proteins, can be degraded. Membrane flow plays a pivotal role in this process. To find out whether phosphatidylinositol 3-kinase is also required for autophagy, we tested the effects on autophagy of two structurally unrelated phosphatidylinositol 3-kinase inhibitors, wortmannin and 2-(4-morpholinyl)-8-phenylchromone (LY294002). The addition of low concentrations of each of these inhibitors to incubations of hepatocytes in the absence of amino acids resulted in a strong inhibition of proteolysis. The antiproteolytic effect of wortmannin (IC50 30 nM) and LY294002 (IC50 10 microM) was accompanied by inhibition of autophagic sequestration and not by an increase in lysosomal pH or a decrease in intracellular ATP. No further inhibition of proteolysis by the two compounds was observed when autophagy was already maximally inhibited by high concentrations of amino acids. 3-Methyladenine, which is commonly used as a specific inhibitor of autophagic sequestration, was an inhibitor of phosphatidylinositol 3-kinase, thus providing a target for its action. It is proposed that phosphatidylinositol 3-kinase activity is required for autophagy. 3-Methyladenine inhibits autophagy by inhibition of this enzyme.

Adenine↗