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Biomedical subjects

Peter Neuhaus

Publications and source records attributed to Peter Neuhaus.

At least 91 records · Page 5Linked to original sources
PubMed2004

Donor hypertension increases graft immunogenicity and intensifies chronic changes in long-surviving renal allografts.

BACKGROUND: Marginal donor organs are used increasingly for transplantation. To define the influences of donor hypertension, we compared the behavior of kidney allografts from hypertensive and normotensive donors in an established rat model of chronic rejection. METHODS: Donor hypertension was induced by partial occlusion of the right renal artery with a silver clip. After 10 weeks, the left kidney was removed and transplanted. Normotensive animals served as controls. All recipients were treated with a low dose of cyclosporine for 10 days (1.5 mg/kg). Blood pressure and proteinuria were determined weekly four times after transplantation. To examine the effects of donor hypertension on late events, grafts (n=6/time point) were examined morphologically and by quantitative reverse transcriptase-polymerase chain reaction analysis at serial intervals. RESULTS: Recipients of kidneys from hypertensive donors developed systemic hypertension in contrast with normotensive controls (P<0.05). Allografts from hypertensive animals showed accelerated deterioration in structure and function after transplantation. Proteinuria became significantly elevated as early as 6 weeks (P<0.05) compared with controls and increased progressively thereafter (P<0.005). Grafts from hypertensive donors, histologically normal at the time of engraftment, developed significant morphologic deterioration after 12 weeks (P<0.01). Changes in allografts from normotensive donors remained minor. mRNA of proinflammatory mediators in hypertensive donor grafts (P<0.01) was up-regulated before transplantation and increased progressively over time (P<0.01). CONCLUSIONS: Donor hypertension intensifies the chronic injury associated with allogeneic kidney transplantation in the rat model used. This condition also leads to induction of recipient hypertension and may be a more important risk factor for chronic graft dysfunction than previously appreciated.

Animals↗
PubMed2004

Parathyroid hormone venous sampling before reoperative surgery in renal hyperparathyroidism: comparison with noninvasive localization procedures and review of the literature.

OBJECTIVES: To analyze the predictive values of selective venous sampling (SVS) in our own experience and in a systematic meta-analysis of the international literature and to compare them with the results of noninvasive localization studies before reoperative parathyroid surgery. DATA SOURCES: Twenty-one consecutive patients with persistent or recurrent renal hyperparathyroidism underwent preoperative SVS and noninvasive imaging. These data were added to a systematic review of the literature on localization studies before reoperative surgery. The literature search included localization studies, recurrent hyperparathyroidism, and reoperation. STUDY SELECTION Prospective and retrospective studies that provided at least the true-positive rate of 1 procedure were included. Data from initial surgery, hyperfunctioning autografts, and case reports were excluded. DATA EXTRACTION: Thirty-one publications reported on SVS (n = 22), technetium Tc 99m sestamibi scintigraphy (n = 17), thallium-technetium scintigraphy (n = 11), ultrasonography (n = 18), magnetic resonance imaging (n = 12), and computed tomography (n = 13). The overall analysis was performed by dividing the overall number of true- and false-positive results by the total number of patients. DATA SYNTHESIS: Localization by SVS was correct in 20 of 21 patients. In 1 patient with 2 localizations, only 1 was predicted correctly. Therefore, the sensitivity of SVS was at least 90%, with no false-positive results. Overall true- and false-positive rates, respectively, in 31 studies were 71% and 9% for SVS, 69% and 7% for technetium Tc 99m sestamibi scintigraphy, 54% and 16% for magnetic resonance imaging, 55% and 15% for thallium-technetium scintigraphy, 50% and 18% for ultrasonography, and 45% and 14% for computed tomography. CONCLUSIONS: With its high sensitivity, SVS is the gold standard in patients with persistent or recurrent renal hyperparathyroidism and negative results of noninvasive localization procedures. The noninvasive procedure of choice is now technetium Tc 99m sestamibi scintigraphy, with high sensitivity and a low rate of false-positive results.

Adolescent↗
PubMed2004

In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD).

The detoxification capacities of single-pass albumin dialysis (SPAD), the molecular adsorbents recirculation system, (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) were compared in vitro. In each experiment 4,100 mL of toxin-loaded human plasma was processed for 6.5 hours. MARS treatment (n = 6) was undertaken in combination with CVVHDF. For SPAD (n = 6) and CVVHDF (n = 6) a high-flux hollow fiber hemodiafilter (identical to the MARS filter) was used. Levels of ammonia, urea, creatinine, bilirubin, and bile acids were determined. Concentrations before and after application of detoxification procedures were expressed as differences and were compared using the Kruskal-Wallis test. Post hoc comparisons for pairs of groups were adjusted according to Bonferroni-Holm. Time, group, and interaction effects were tested using the nonparametric ANOVA model for repeated measurements. SPAD and CVVHDF induced a significantly greater reduction of ammonia levels than MARS. No significant differences were found among SPAD, MARS, and CVVHDF with respect to other water-soluble substances. SPAD induced a significantly greater reduction in bilirubin levels than MARS. Reductions in bile acid levels were similar for SPAD and MARS. When operating MARS in continuous veno-venous hemodialysis mode, as recommended by the manufacturer, no significant differences in the removal of bilirubin, bile acids, urea, and creatinine were found. However, MARS in continuous veno-venous hemodialysis mode was significantly less efficient in removing ammonia than MARS in CVVHDF mode. In conclusion, the detoxification capacity of SPAD is similar to or even greater than that of MARS.

Hemodialysis Solutions↗
PubMed2004

Microscopic tumor cell dissemination in gastric cancer.

PURPOSE: There is still much controversy surrounding the prognostic significance of microscopic tumor cell dissemination in gastric cancer and its correlation with histopathologic parameters. We herein investigate such dissemination, predominantly restricted to the subserosa, in patients with gastric cancer. METHODS: Intraoperative bone marrow aspiration was done in 26 patients undergoing resection of gastric carcinoma. Peritoneal lavage could not be done in 8 of these 26 patients. The R0-resection rate was 84% (n = 22). A cytokeratin-directed antibody and an antibody directed against carcinoembryonic antigen served for the immunocytochemical detection of tumor cells, and the alkaline phosphatase antialkaline phosphatase method was used for visualization. RESULTS: The bone marrow aspirate and peritoneal lavage fluid were immunocytochemically positive in 31% and 56% of the patients, respectively. There was a trend (P = 0.10) towards higher overall survival rates in patients with negative bone marrow samples than in those with tumor cells detected in bone marrow samples. Analyzing the results of peritoneal lavage did not reveal any significant differences. In the group of T1/2 cancers, survival was significantly worse if the bone marrow was positive for tumor cells, with 3-year survival rates of 25% vs 77%, respectively (P < 0.05). CONCLUSION: The rates of tumor cell dissemination into the bone marrow or into the peritoneal cavity were within the scope of previous reports. Dissemination into the bone marrow resulted in significantly impaired survival in patients with T1 and T2 gastric carcinoma, and it did not correlate with known prognostic parameters.

Bone Marrow↗
PubMed2004

Clinical practice of nutrition in acute liver failure--a European survey.

BACKGROUND: Evidence-based guidelines for artificial nutrition in hyperacute (HLF), acute (ALF) and subacute liver failure (SLF) cannot be given at present due to scarcity of clinical studies. METHODS: Current nutritional practice was surveyed using a questionnaire which was answered by 33 hepatology units (2-170 cases/year) in 11 European countries. RESULTS: All units used specific nutrition support regimes in liver failure patients. Eight units (385 patients/year) preferentially used tube-feeding with standard diets, 25 units (377 patients/year) used parenteral nutrition (PN). For PN glucose was infused at 4.0 g/kg d (median; range 0.6-10.0). Intravenous fat was given only by some units: (18/33) in HLF at 0.9 g/kg d (0.3-2.0), (21/33) in ALF at 1.0 g/kg d (0.3-2.0), and (23/33) in SLF at 1.0 g/kg d (0.3-3.0). Amino acid solutions, predominantly enriched in branched-chain amino acids, were used in HLF (19/33 units) and in ALF (23/33) at 0.9 g/kg d (0.5-1.5) and in SLF (24/33) at 1.0 g/kg d (0.7-1.5). CONCLUSION: Hepatology units use a considerable variety of specific nutrition support strategies in liver failure. About 50% of patients receive enteral nutrition. Dosage and monitoring of PN is similar to other critical illness with a wide variety of infusion rates and accepted ranges of substrate plasma concentrations.

Critical Care↗
PubMed2004

Flow pattern and shear stress distribution of distal end-to-side anastomoses. A comparison of the instantaneous velocity fields obtained by particle image velocimetry.

OBJECTIVE: To describe the local hemodynamics and pressure losses of crural bypass anastomoses using instantaneous velocity fields acquired by particle image velocimetry (PIV). METHODS: Silastic models of a Taylor patch, a Miller cuff and a femoro-crural patch prosthesis (FCPP) were attached to a circuit driven by a Berlin Heart, providing a pulsatile flow with an amplitude of 450 to 25 ml/min (mean 200 ml/min). An outflow resistance of 0.5 mmHg/ml/min (peripheral resistance units, PRU) was modeled using small silastic tubes providing a phase shift of -12 degrees between flow and pressure curves. The working fluid consisted of a glycerine/water mixture with a viscosity of 4 mPas. Hollow glass spheres with a mean size of 9-13 microm were used as tracer particles. Instantaneous velocity fields were obtained by means of PIV and shear rates as well as shear stresses were calculated. Triggered by the flowmeter signal, 10 measurements at 100 ms intervals per cardiac cycle were obtained. The pressures were measured on the inflow and at both distal outflows. The resulting mean pressure losses due to flow separation and distal fluid acceleration were calculated. RESULTS: Inside the Taylor patch anastomosis a large flow separation at the hood containing a clockwise rotating vortex was found. Additionally a smaller flow separation at the heel and a flow stagnation zone on the floor of the recipient artery were observed. Conversely, inside the Miller cuff a counterclockwise rotating vortex was seen inside a large heel flow separation. The FCPP also showed typical separation areas at the hood and heel of the anastomosis, although these were smaller compared to the other anastomoses. Inside the FCPP anastomosis no vortex creation was observed throughout the cardiac cycle. The mainstream velocities at the inlet levels were comparable for the three anastomoses. A significant fluid acceleration was present at the antegrade as well as the retrograde outlets of the Taylor and Miller cuff, while the fluid acceleration at the antegrade outflow of the FCPP was small, which was attributed to the end-to-end configuration of the antegrade FCPP leg. The calculated normalized antegrade and retrograde pressure losses for the Taylor form were 0.90 and 0.88, for the Miller cuff 0.89 and 0.86 and for the FCPP 0.94 and 0.86, respectively. The shear stresses inside the flow separations of the three anastomoses were significantly lower than normal wall shear stresses. High shear stress levels were found inside the transition zones between flow separation and high velocity mainstream. CONCLUSIONS: The flow pattern inside cuffed or funnel shaped anastomoses consists of large flow separation zones, which are thought to be associated with intimal hyperplasia development. In addition, fluid accelerations at the distal outlets result in pressure losses, which may contribute to impaired crural perfusion.

Anastomosis, Surgical↗
PubMed2004

The delay of rearterialization after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction.

BACKGROUND/AIMS: Graft reperfusion in liver transplantation is usually performed by initial portal reperfusion (IPR) and delayed rearterialization. Its influence on graft microcirculation is unknown. This study aimed to assess sinusoidal perfusion in dependence to this reperfusion technique during human living-donor liver transplantation. METHODS: Hepatic microcirculation was measured both in the donor and the recipient (n=14) by using the orthogonal polarization spectral imaging technique. By using initial portal reperfusion, the mean time interval between portal venous and hepatic arterial reperfusion was 27.7+/-13.3 min. RESULTS: Hepatic nutritive perfusion, as given by the functional sinusoidal density and the volumetric blood flow, was found significantly decreased during portal reperfusion when compared to baseline. Rearterialization resulted in hyperperfusion of individual sinusoids at a decreased density of the sinusoidal network. Interestingly, the time interval between portal venous and hepatic arterial reperfusion significantly correlated with the changes of the liver grafts' microcirculation. CONCLUSIONS: The study indicates graft microcirculatory dysfunction as a major determinant of postischemic liver injury. Moreover, microvascular impairment was significantly influenced by the interval between portal venous and hepatic arterial reperfusion, which suggests the reinforcement of the pathomechanism of injury involving hypoxia and rapid graft rewarming due to initial portal reperfusion.

Adult↗
PubMed2004

Fibrosis progression after liver transplantation in patients with recurrent hepatitis C.

BACKGROUND/AIMS: Aim of our study was to analyze fibrosis progression after liver transplantation (OLT) in hepatitis C virus (HCV)-infected patients based on protocol liver biopsies and to identify risk factors, which may play a role in the development of severe fibrosis stages. METHODS: One hundred and eighty-three liver graft recipients who had a histological follow-up evaluation of 1 year after OLT were analyzed. Overall 1039 protocol liver biopsies were performed after 1-, 3-, 5-, 7- and 10 years and staged according to the Scheuer score. RESULTS: The fibrosis progression rate was not linear. The fibrosis scores were 1.2 after one, 1.7 after three, 1.9 after five, 2.1 after 7 and 2.2 after 10 years. The 39 recipients with fibrosis stages 3 or 4 in the 1-year biopsy had a significantly reduced survival rate, while fibrosis stage 0-2 indicated excellent survival. Independent risk factors for progression of fibrosis at 1 year were HCV genotype 1 and 4 (P=0.01) and donor age>33 years (P=0.01), whereas risk factors for development of cirrhosis (30/183 recipients (16%)) were donor age (P=0.002) and multiple steroid pulses (P=0.05). CONCLUSIONS: These data provide information on the course of recurrent hepatitis C and may be helpful to individualize the treatment of transplanted patients.

Adult↗
PubMed2004

Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold hypoxia.

BACKGROUND/AIMS: Hepatic injury induced by ischemia/reperfusion following surgery, transplantation, or circulatory shock combined with resuscitation is a major clinical problem. METHODS: In this study, hypoxic and inflammatory conditions were mimicked by exposing human hepatocytes to N(2) (at 4 and 37 degrees C) or to cytokines/endotoxin to investigate the potential protective effects of heme oxygenase-1 (HO-1). Incubation of human hepatocytes with single cytokines (IFN-gamma, IL-1beta, TNF-alpha) or LPS, as well as a combination of all four stimuli (CM, cytomix) caused a time-dependent HO-1 mRNA expression over 12h and a decline by 24 h. In parallel, we observed a time-dependent membrane leakage for LDH and AST and a maximum HO-1 protein expression between 3-24 h. RESULTS: Warm and cold hypoxia showed similar results in HO-1 mRNA and protein expression and the release of LDH and AST. CoPP, a potent HO-1 inducer, and bilirubin, a co-product of the HO-pathway, protected human hepatocytes from warm and cold hypoxia. HO-1 enzyme activity was highest during warm hypoxia, followed by cold hypoxia and CM which was confirmed by intracellular Fe(2+) formation. CONCLUSIONS: Taken together, we demonstrated, that HO-1 induction protected human hepatocytes against warm and cold hypoxia. Our results also suggest that HO-1 induction may have therapeutic potential against inflammatory insults.

Aspartate Aminotransferases↗
PubMed2004

Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats.

BACKGROUND: Bacterial translocation is one important cause of nosocomial infections following major abdominal surgery. Oral administration of probiotics has been proposed to diminish bacterial translocation. MATERIAL AND METHODS: In total 68 rats were divided into seven groups: five of the groups received standard rat chow and were subjected to either sham-operation, 70% liver resection, colonic anastomosis, or a combination of 30 or 70% liver resection with synchronous colonic anastomosis, respectively. In two additional groups with synchronous operation, a combination of four different lactic acid bacteria and four fibers was administered two times daily pre- and postoperatively. Bacterial concentrations in cecum, mesenteric lymph nodes, liver, and spleen were analyzed and blood cultures were taken 48 h after operation. Furthermore, the following parameters were assessed: histological changes in the intestine, intestinal paracellular permeability (Ussing chamber), bursting pressure of the colonic anastomosis, and mitosis rate of the remnant liver. RESULTS: Bacterial translocation was observed in all rats, except in the sham group. Following liver resection, the highest bacterial concentrations were seen in liver and spleen, following colon anastomosis in the mesenteric lymph nodes. Bacterial translocation was increased in the animals with combined operation, in parallel to the extent of liver resection. In rats with colon anastomosis, bacterial concentration in the cecum was also higher than in the sham group. Application of probiotics significantly decreased bacterial concentration in the lymph nodes. In addition, animals with a high cecal concentration of lactobacilli had less translocation than the others. No histological changes were observed in the intestine. Paracellular permeability for ions, but not for the larger molecule lactulose, was increased in the colon in all groups with colon anastomosis. The bursting pressure of the colon anastomosis was not significantly different between the groups. Seventy percent liver resection led to a high rate of hepatocyte mitosis, whereas combination with colon anastomosis impaired the regeneration process. CONCLUSION: Synchronous liver resection and colon anastomosis led to increased bacterial translocation compared to the single operations in the rat model. It is possible to diminish this process by oral administration of probiotics. Bacterial overgrowth in the cecum and impaired hepatic regeneration, but not histological changes or alterations of paracellular permeability, are potential pathogenic mechanisms for translocation in this setting.

Administration, Oral↗
PubMed2004

Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury.

BACKGROUND: Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia. METHODS: Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals. RESULTS: Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-kappaB/Rel-binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity. CONCLUSIONS: MP (probably by downregulation of NF-kappaB-binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.

Animals↗
PubMed2004

Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity.

AIMS: To characterize the interindividual variability and the individual CYP involved in the formation of alpha-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen from tamoxifen. METHODS: Microsomes from 50 human livers were used to characterize the interindividual variability in the alpha-hydroxylation, N-desmethylation and N-didesmethylation of tamoxifen. Selective inhibitors and recombinant enzymes were used to identify the forms of CYP catalysing these reactions. RESULTS: The rates of formation of alpha-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen were highly variable, and correlated with each other (P < 0.0001). The respective ranges were 0.7-11.4, 25.7-411, and below the limit of quantification--4.4 pmol mg(-1) protein min(-1). Formation of all metabolites was observed with expressed recombinant CYP3A4, inhibited by troleandomycin (65, 77 and 35%, respectively, P < 0.05) and associated with CYP3A4 expression (rs = 0.612, rs = 0.585 and rs = 0.430, P < 0.01, respectively). CONCLUSIONS: Formation of alpha-hydroxy-, N-desmethyl- and N-didesmethyl-tamoxifen in vitro is highly variable and mediated predominantly by CYP3A4.

Adolescent↗
PubMed2004

Living-donor liver transplantation--European experiences.

To overcome the problem of organ shortage in recent years, liver transplantation from a living donor has been established. From a surgical standpoint, split liver transplantation and living-donor liver transplantation (LRLTx) are very complex surgical procedures requiring meticulous surgical techniques. LRLTx was first developed and performed in Asia and the USA. In the beginning of the 1990s, LRLTx was introduced in Europe. In Europe, 46 of 118 registered transplant centres had already performed LRLTx in December 2001. Up to this time point, more than 800 LRLTx were performed since 1991. Medical discussions in the field of LRLTx include the need for high quality procedures, simplifying donor evaluation, optimizing surgical techniques and immunosuppression, all of which are current problems. The perioperative morbidity of the donor including all minor complications is stated to be 10-25%. Biliary complications of 5-10% are the major portion. The results of LRLTx for paediatric and adult recipients are comparable. The perioperative complication rate is slightly higher in LRLTx than after cadaver transplantation. This can be explained by the complexity of the surgical intervention with technical complications and the limited experience so far. Other reasons that can be ascertained are extended indications with higher incidence of tumour recurrence and infectious complications in these recipients. In recent years, LRLTx has emerged as a clinically safe alternative to cadaver transplantation in many cases and has further extended the donor pool. LRLTx has been shown to be a good option for patients with liver disease in which a long waiting time is not permitted.

Dissection↗
PubMed2004

Hepatocyte growth factor and c-Met expression in rat and human liver fibrosis.

BACKGROUND: Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes in vitro. AIMS: Substitution of HGF was suggested for human liver disease on the basis of animal experiments. The cellular sources of HGF and its receptor, c-Met, in liver disease in vivo are not well defined. METHODS: We characterised HGF and c-Met expression in normal and cirrhotic human livers and rat livers at various time points after CCl4 administration by in situ hybridisation and immunohistology. HGF transcripts were restricted to resting and activated stellate cells in rat and human liver. RESULTS: In rat liver, HGF showed peak levels 6-12 h following acute intoxication, and remained increased after repeated CCl4 injury. HGF transcript levels were very low in normal human liver, but excessively raised in fibrosis/cirrhosis. In contrast, HGF immunoreactivity was found not only in perisinusoidal/periductular cells but also in cholangiocytes of proliferating ductules. c-Met RNA and protein was expressed in hepatocytes, cholangiocytes, and arteriolar endothelial cells. CONCLUSIONS: The HGF-specific immunostaining of proliferating cholangioles in the absence of HGF RNA suggests c-Met-mediated uptake of HGF and paracrine stimulation of cholangiocellular proliferation. Mitogenic effects of HGF on hepatocytes may therefore be accompanied by undesired cholangiogenesis and angiogenesis limiting its therapeutic value in chronic liver disease.

Animals↗
PubMed2004

Prospective evaluation of the clinical utility of different methods for the detection of human cytomegalovirus disease after liver transplantation.

Standardized human cytomegalovirus (HCMV) assays were prospectively evaluated to predict HCMV disease. In 135 consecutive adult liver transplantations, pp65-antigenemia, quantitative HCMV-DNA and qualitative pp67-messenger-RNA were determined weekly. No ganciclovir prophylaxis or preemptive treatment was used. One hundred and ten (81.5%) patients showed no HCMV-infection, 25 patients were positive in at least one of the HCMV-tests (18.5%). Four suffered from HCMV viral syndrome (3.0%) and another four from tissue invasive disease. In total, pp65-antigenemia was detected in 18, HCMV-DNA in 22 and pp67-mRNA in 18 patients. The sensitivity and negative predictive value (NPV) for HCMV-disease was 100% for all tests. The PPV for symptomatic HCMV-infection was 47% for pp67 mRNA. In contrast, the PPV of pp65-antigenemia (using a threshold of > 2/200 000 cells) and quantitative PCR (using a cutoff of > 5000 copies/mL) were 80% and 89%, respectively. A cost analysis revealed symptom-triggered or preemptive treatment was less expensive than general ganciclovir prophylaxis, if the incidence of CMV disease was low (<30%). Quantitative human cytomegalovirus (HCMV)-DNA and pp65-antigen assays have a comparable sensitivity and can therefore predict the onset of HCMV symptoms at an early stage. Compared with general prophylaxis, symptom-triggered or preemptive treatment based on one of these assays might reduce the costs and also the danger of ganciclovir resistance.

Antigens, Viral↗
PubMed2004

Ca(2+) channel properties in neuroendocrine tumor cell cultures investigated by whole-cell patch-clamp technique.

Neuroendocrine tumor (NET) cells of the gastroenteropancreatic system express a variety of voltage-operated Ca(2+) channels (VOCCs). In addition, NET cells release hormones and biogenic amines in distinct patterns, leading to typical hypersecretion syndromes. Interestingly, these patterns depend on the primary location of the NET. The aim of this study was to investigate a possible link between clinically distinct entities of NETs and specific properties of VOCCs. Using whole-cell patch-clamp technique, electrophysiological data were obtained from permanent NET cell cultures as well as from primary cultivated NET cells from foregut and midgut tumors. Definite Ca(2+) channel characteristics were analyzed by a color-coding method. As a result, we could demonstrate specific Ca(2+) channel characteristics in NET cells from midgut tumors that were not found in NET cells from a foregut location. This may be important functionally with respect to different cell biological functions of NET cells. In summary, clear differences exist in the VOCC pattern in NET cells from foregut versus midgut. This may be functionally relevant in the hypersecretion syndrome predominantly found in foregut NETs. Therefore, these data on the characteristics of VOCCs could be useful in the development of a novel therapy for NET disease; for example, specific VOCC subtype modulators may help.

Calcium Channels↗