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A Eggert

Publications and source records attributed to A Eggert.

At least 37 records · Page 2Linked to original sources

Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression.

BACKGROUND: Disruption of apoptotic pathways may be involved in tumor formation, regression, and treatment resistance of neuroblastoma (NB). TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell lines. PROCEDURE: In this study we analyzed the expression and function of TRAIL, its agonistic and antagonistic receptors, and important intracellular signaling elements in 18 NB cell lines. RESULTS: Semiquantitative RT-PCR revealed that TRAIL-R2 and TRAIL-R3 are the main TRAIL-receptors used by NB cells. Sensitivity to TRAIL-induced apoptosis did not correlate with mRNA expression of TRAIL receptors or cFLIP. Surprisingly, caspase-8 and caspase-10 mRNA was detected in only 5 of 18 NB cell lines. Interestingly, only these five NB cell lines were susceptible to TRAIL-induced apoptosis in a time- and dose-dependent manner. CONCLUSIONS: Treatment with 5-aza-2'-deoxycytidine restored mRNA expression of caspase-8 and -10 and TRAIL sensitivity of resistant cell lines, suggesting that gene methylation is involved in caspase inactivation. Since many cytotoxic drugs induce caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might be an important mechanism of resistance to chemotherapy in NB.

Apoptosis↗

Different effects of TrkA expression in neuroblastoma cell lines with or without MYCN amplification.

BACKGROUND: Expression of the neurotrophin receptor TrkA is associated with a favorable prognosis in neuroblastoma (NB) and promotes growth inhibition and neuronal differentiation. Aggressive, MYCN-amplified NB tumors express little or no TrkA mRNA, suggesting that MYCN overexpression may inhibit TrkA expression. PROCEDURE: To study the interactions of TrkA expression and MYCN amplification in NB, we stably expressed the TrkA receptor in the MYCN single copy cell lines SH-SY5Y and NB69 as well as in the MYCN amplified cell lines CHP134 and IMR5. RESULTS: All four transfected cell lines demonstrated high TrkA expression and similar activation of the TrkA receptor and of mitogen-activated protein kinases as well as induction of immediate-early genes in response to nerve growth factor (NGF). Introduction of TrkA restored NGF responsiveness of SH-SY5Y and NB69 cells, as demonstrated by morphologic differentiation, growth inhibition, and enhanced survival in serum-free medium. However, no morphologic, growth, or survival responses to NGF were detected in MYCN-amplified CHP134 and IMR5 TrkA transfectants. CONCLUSIONS: Thus, transfection of TrkA into MYCN amplified NB cell lines only partly restored the TrkA/NGF signaling pathway, suggesting additional inhibitory effects of MYCN overexpression on TrkA signaling.

Cell Division↗

Relative quantitative RT-PCR protocol for TrkB expression in neuroblastoma using GAPD as an internal control.

An RT-PCR protocol for the relative quantitative measurement of TrkB transcripts using glyceraldehyde-3-phosphate-dehydrogenase (GAPD) transcripts as an internal control is described. Both TrkB and GAPD sequences were co-amplified in the exponential phase of amplification using 5'-biotinylated primers. The PCR products were subjected to PAGE, electro-transferred to nylon membrane and detected by a chemiluminescent procedure using alkaline phosphatase conjugated with avidin. Signals detected on X-ray film were analyzed by densitometry. The ratio between TrkB and GAPD expression levels was determined to normalize the expression levels of TrkB transcripts. Initially, strong signals of GAPD transcripts led to overexposure of X-ray film compared to those of TrkB, which causes difficulties in the accurate determination of the TrkB/GAPD ratio. To circumvent this problem, uniformly biotinylated GAPD primers were replaced with a mixture of biotinylated and non-biotinylated GAPD primers of the same sequence and concentration. GAPD signals detected on X-ray film were proportionally decreased as the amount of biotin-labeled primers was reduced in the total GAPD primers. This modification enabled both GAPD and TrkB signals to be analyzed within the linear range of X-ray film detection without affecting the amplification efficiency of TrkB sequence. Use of composite primers may have a wide range of applicability in quantitative analysis of nucleic acids.

Biotinylation↗

High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas.

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. Neuroblastoma (NB) is a common pediatric tumor of neural crest origin, which is biologically and clinically heterogeneous. Increased tumor vascular index correlates with poor outcome of NB. To determine which angiogenic factors contribute to NB angiogenesis and thereby support tumor progression, we examined the expression of eight angiogenic factors [vascular endothelial growth factor (VEGF), VEGF-B, VEGF-C, basic fibroblast growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor alpha, and platelet-derived growth factor (PDGF)] by semiquantitative RT-PCR in 37 NB primary tumors and in 22 NB cell lines. We also analyzed the relationship between angiogenic factor expression and clinicopathological factors as well as patient survival. All eight angiogenic factors examined were expressed at various levels in NB cell lines and tumors, suggesting their involvement in NB angiogenesis. The expression levels of most angiogenic factors were correlated with each other, suggesting their synergy in regulating the angiogenic process. Significantly higher expression levels of VEGF, VEGF-B, VEGF-C, basic fibroblast growth factor, Ang-2, transforming growth factor alpha, and PDGF-A (P < 0.0001-0.026) were found in advanced-stage tumors (stages 3 and 4) compared with low-stage tumors (stages 1, 2, and 4S). Expression of PDGF-A was significantly associated with patient survival (P = 0.04). The redundancy in angiogenic factor expression suggests that inhibition of VEGF bioactivity alone might not be a sufficient approach for antiangiogenic therapy of human NB.

Angiogenesis Inducing Agents↗

[Endoguide Reinbek--a device for trocarless insertion of instruments in endoscopic surgery].

UNLABELLED: The Endoguide Reinbek (EGR) is a device that allows the insertion and use of laparoscopic instruments without a trocar-sheath unit. It consists of a steel rod 40 cm long and 10 mm in diameter, with pointed ends that can be screwed off. One end is 10 mm in diameter and the other, 6 mm. Both points can be covered by a removable handle. APPLICATION: The EGR is introduced into the abdominal cavity via a 10-mm port. Camera supervision is applied to select the exact position for any instrument. The tip of the EGR perforates the abdominal wall from inside, thus preventing any damage to blood vessels of viscera. A small skin incision is made over the tip once the skin bulges outward at the body surface. Once outside the abdomen the tip is removed, leaving a socket into which any instrument, e.g. a forceps, fits. The instrument is "guided" into the abdominal cavity by simply pushing it axially to the EGR. Inside the abdomen the EGR is disconnected from the instrument and withdrawn. The instrument is used without a port. There is no more loss of gas than when trocars are used. The EGR is especially useful for instruments that do not have to be changed during the operation and for the application of endoscopic drains. However, instruments can also be changed. The main advantage of the EGR is cost reduction, especially if disposable trocars have been used thus far. If reusable trocars have been applied so far there is a significant reduction in the maintenance effort (dismanting, cleaning, reassembly and resterilization of trocars). Moreover, endoscopic instruments can be positioned more safely and more precisely.

Cost Control↗

Understanding the dendritic cell lineage through a study of cytokine receptors.

Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function.

Animals↗

[Repair of inguinal hernia--a determination of the current status].

Inguinal hernias show a considerable variability in size and morphology. Hernia repair can be performed with good results using standard procedures or techniques with prosthetic mesh implantation. However, recurrence and complication rates have to be reduced further. To achieve that goal we propose a concept of stage adjusted hernia repair: Small indirect hernias: Zimmermann repair or transversalis fascia hernioplasty (Shouldice, Lotheissen-Mc Vay). Large indirect hernias: transversalis fascia hernioplasty or prosthetic mesh. Direct hernias: prosthetic mesh or transversalis fascia hernioplasty. Recurrent hernia: large mesh or transversalis fascia hernioplasty.

Hernia, Inguinal↗

Acetonitrile serum concentrations and cyanide blood levels in a case of suicidal oral acetonitrile ingestion.

Acute acetonitrile toxicity is mainly dependent on the release of cyanide via hepatic metabolism. Although evaluated in animals, few data are available concerning the toxicokinetic parameters of acetonitrile and acetonitrile-liberated cyanide in human. This paper reports a case of suicidal oral acetonitrile ingestion of about 5 mL without severe symptoms of intoxication in a previously healthy adult male with a body weight of 60 kg. Acetonitrile serum concentrations as well as cyanide blood levels were determined over the whole hospitalization. The elimination half-lives calculated from these data were 32 h for acetonitrile and 15 h for cyanide. After sodium thiosulfate bolus application, the cyanide blood level rapidly decreased to 10% of the initial value, indicating that sodium thiosulfate sufficiently detoxifies acetonitrile-liberated cyanide. Since cyanide levels again increased to maximal values about 4.5 h after sodium thiosulfate application, continued thiosulfate therapy is required as predicted by the long elimination half-lives of acetonitrile and acetonitrile-liberated cyanide. Determination of cyanide and acetonitrile concentrations is recommended for the estimation of optimal individual sodium thiosulfate dosage.

Acetonitriles↗

[Falsification of breath alcohol concentration measurement. An experimental and case report].

As a rule, in our comparison of breath alcohol and blood alcohol concentration levels both readings were in agreement. Nevertheless, we repeatedly observed readings showing significant differences for which there was no apparent explanation. In two cases where discrepancies were extreme (breath alcohol concentration greater than 2.0%; blood alcohol concentration, 0.0%) we discovered that the cause was sniffing. The effects of various pharmaceutical drugs were tested. Experimentally the inhalation of liquid gas resulted in ostensible breath alcohol concentration levels of more than 2%. These experiments were reproducible. Consequences for the exployment of alcohol breath testing devices are discussed.

Adult↗

[Interdigestive motility in duodenal diverticula].

In a controlled study of patients with cholelithiasis and patients with cholelithiasis and duodenal diverticula a significantly higher rate of bacteriocholia and miscolonization of the duodenum with intestinal bacteria as well as a significantly higher rate of interdigestive disorder of motility with missing of a wandering activity front was found in the group of patients with diverticula in 11 out of 25 patients. If a cyclic sober motility is found in patients with diverticula, the duration of cycle, the maximum pressure of the interdigestive complexes and its wandering speed are not significantly different from those of the control group. The studies allow the interpretation that retention of food in the diverticula is not the reason for the bacterial miscolonization of the duodenum and the biliary tract, but in patients with diverticula a disturbed self-cleaning mechanism is present. The pathogenesis of duodenal diverticula is not clear.

Ampulla of Vater↗

[Effect of intraoperative local polyvinylpyrrolidone iodine administration on the risk of wound infection following appendectomy].

A study conducted into 91 appendectomised patients revealed wound infection rates to worsen from eight to 26 per cent (p less than 0.05) in the wake of locally delimited intra-operative application of povidone-iodine solution, two per cent in concentration. No other factors were found to be responsible for that aggravation. Tissue toxicity was found to outweight bactericidal effects, even with application in diluted and PVP-bonded form. Hence, povidone-iodine solutions not even in diluted form should ever be applied to wound treatment.

Adult↗

Injuries to the metatarsophalangeal joints in athletes.

Injury to the metatarsophalangeal joints in sports has become an increasing problem with the advent of more flexible shoewear and artificial playing surfaces. These injuries vary from mild sprains to severe tearing of the capsuloligamentous complex including avulsion fractures. This may include a compression fracture of the metatarsal head in the more severe cases. At the extreme, dislocation or fracture-dislocation of the metatarsophalangeal joint occurs. The findings in 62 cases of these injuries in Rice University athletes from 1971 to 1985 are presented. Treatment follows a standard regimen of ice, taping and anti-inflammatory medication with gradual return to sports activity as symptoms allow. Recommendations for preventive therapy include stiffening the forefoot in athletic shoes or the use of an orthotic device. This should reduce the incidence of long-term sequelae.

Adult↗

[Intraoperative orthograde intestinal irrigation. On a method used in colonic surgical emergencies].

With the help of intraoperative orthograde irrigation of the colon it is possible to handle emergency abdominal colectomies like elective operations of the colon. The resection of the large bowel following the intraoperative orthograde irrigation is determined by the causal malady as cancer, diverticulitis and perforation. Lymphadenectomy and colonic resection with primary anastomosis succeeded without preventative colostomy. One of the nine, mostly geriatric patients undergoing an emergency resection of the left colon or rectosigmoid died of pulmonary embolism. No typical complications as anastomotic leakage or disturbance of wound healing ensued, common morbidity came to four of the nine patients. For the intraoperative orthograde irrigation of the colon accurate surgical engineering and tactics are absolutely necessary as described. It is possible to renounce the radical colectomy, colostomy and staged procedures in the treatment of emergency colon resection.

Aged↗