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Robert Zimmermann

Publications and source records attributed to Robert Zimmermann.

At least 19 recordsLinked to original sources
PubMed2006

Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism.

The mobilization of free fatty acids from adipose triacylglycerol (TG) stores requires the activities of triacylglycerol lipases. In this study, we demonstrate that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major enzymes contributing to TG breakdown in in vitro assays and in organ cultures of murine white adipose tissue (WAT). To differentiate between ATGL- and HSL-specific activities in cytosolic preparations of WAT and to determine the relative contribution of these TG hydrolases to the lipolytic catabolism of fat, mutant mouse models lacking ATGL or HSL and a mono-specific, small molecule inhibitor for HSL (76-0079) were used. We show that 76-0079 had no effect on TG catabolism in HSL-deficient WAT but, in contrast, essentially abolished free fatty acid mobilization in ATGL-deficient fat. CGI-58, a recently identified coactivator of ATGL, stimulates TG hydrolase activity in wild-type and HSL-deficient WAT but not in ATGL-deficient WAT, suggesting that ATGL is the sole target for CGI-58-mediated activation of adipose lipolysis. Together, ATGL and HSL are responsible for more than 95% of the TG hydrolase activity present in murine WAT. Additional known or unknown lipases appear to play only a quantitatively minor role in fat cell lipolysis.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed2006

Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase.

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.

Adipocytes↗
PubMed2006

Hepatitis B vaccination status among healthy adults in Germany.

OBJECTIVES: The hepatitis B vaccination policy in Germany was intensified by the implementation of hepatitis B vaccination for adolescents in the vaccination calendar in 1995. To investigate the effect of this measure on the hepatitis B vaccination coverage of healthy adults, we analysed the hepatitis B vaccination status of blood donors. Furthermore, the reasons for vaccination and the relationship between vaccination status and age, sex, and current profession were studied. METHOD: Using a standardised questionnaire, randomly incoming whole blood donors were asked for hepatitis B vaccination status, the reason for vaccination, gender, age and current profession. Multiple logistic regression analysis with vaccination status as dependent variable and age, gender and current profession as explanatory variables was performed. RESULTS: Overall, 1519 (22.3%) of the 6812 interviewed whole blood donors were vaccinated against hepatitis B. Younger age was significantly associated with higher acceptance of hepatitis B vaccination with already 44.1% of whole blood donors aged 18-29 years being hepatitis B immunised. Beside health care workers, teaching professions and students showed the highest hepatitis B vaccination rate. Foreign travel was nearly an equivalently important reason for hepatitis B vaccination as occupational risks. CONCLUSION: The high hepatitis B vaccination coverage among young and healthy adults indicates the success of the intensified hepatitis B vaccination policy since 1995. However, concentrating education measures on individuals with lower educational level and intensifying hepatitis B vaccination in the context of foreign travel could further increase the acceptance of hepatitis B vaccination.

Adolescent↗
PubMed2006

LPL-mediated lipolysis of VLDL induces an upregulation of AU-rich mRNAs and an activation of HuR in endothelial cells.

Lipoprotein lipase (LPL), the major enzyme for hydrolysis of circulating triglyceride-rich lipoproteins, is bound to the luminal surface of capillary endothelial cells. Products of LPL-mediated lipolysis, such as free fatty acids (FFA) and lipoprotein-remnants, can affect endothelial function and gene expression, and hence vascular homeostasis. In this study we tried to identify lipolysis-induced mRNAs in porcine aortic endothelial cells (ECAP) using a cDNA subtraction method. cDNA obtained from ECAP incubated with LPL and VLDL was subtracted from cDNA from cells cultured under control conditions. Analysis of the identified sequences revealed an upregulation of several mRNAs with adenine and uracil-rich elements (ARE) in their 3'-untranslated regions, such as IL-8, ESM-1 and VCAM-1. HuR, a ubiquitously expressed RNA-binding protein, is known to stabilize ARE-harboring mRNAs. Therefore, we investigated whether HuR is involved in this process and found that lipolysis induced an increased polysomal localization of HuR, which is typical for its activation pathway. In addition, the mRNAs for GM-CSF and TNF-alpha - established ARE-containing targets for HuR-mediated regulation - were upregulated by LPL-mediated lipolysis in ECAP. Differential expression of AU-rich mRNAs in response to LPL-mediated lipolysis might have an impact on physiological processes regulating lipid metabolism or pathophysiological processes promoting endothelial dysfunction and atherogenesis.

Animals↗
PubMed2006

Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.

Adipose triglyceride lipase (ATGL) was recently identified as an important triacylglycerol (TG) hydrolase promoting the catabolism of stored fat in adipose and nonadipose tissues. We now demonstrate that efficient ATGL enzyme activity requires activation by CGI-58. Mutations in the human CGI-58 gene are associated with Chanarin-Dorfman Syndrome (CDS), a rare genetic disease where TG accumulates excessively in multiple tissues. CGI-58 interacts with ATGL, stimulating its TG hydrolase activity up to 20-fold. Alleles of CGI-58 carrying point mutations associated with CDS fail to activate ATGL. Moreover, CGI-58/ATGL coexpression attenuates lipid accumulation in COS-7 cells. Antisense RNA-mediated reduction of CGI-58 expression in 3T3-L1 adipocytes inhibits TG mobilization. Finally, expression of functional CGI-58 in CDS fibroblasts restores lipolysis and reverses the abnormal TG accumulation typical for CDS. These data establish an important biochemical function for CGI-58 in the lipolytic degradation of fat, implicating this lipolysis activator in the pathogenesis of CDS.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed2006

The new generation of platelet additive solution for storage at 22 degrees C: development and current experience.

The storage of platelets (PLTs) in PLT additive solutions (PASs) might have several advantages. It can reduce allergic and febrile transfusion reactions, facilitate AB0-incompatible PLT transfusions, enable pathogen inactivation, and make more plasma available for other purposes (eg, for fractionation). For this reason, there has been considerable focus on the development of new PASs that assure maintenance of good PLT quality throughout storage. Several compounds in PASs such as citrate, acetate, phosphate, potassium, and magnesium have all turned out to be important, and the same applies to the necessary amount of glucose as determined by the plasma carryover. The latest generation of PASs, the modified PAS-III and Composol-PS, contains most or all of those compounds. Recently published data on the in vitro quality of either buffy coat- or apheresis-derived PLT concentrates stored in 70% or even 80% of PAS might encourage transfusion specialists to consider using these PASs in routine blood banking. However, because in vitro tests do not adequately predict clinical effectiveness of PLTs after transfusion, in vivo studies are still needed to assess the quality of PAS-stored PLTs.

Blood Platelets↗
PubMed2006

Two techniques for the preparation of cell-scaffold constructs suitable for sinus augmentation: steps into clinical application.

The objective of this clinical trial was the analysis of 2 methods for engineering of autologous bone grafts for maxillary sinus augmentation with secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of mandibular periosteum were cultured in a good manufacturing practice laboratory (2 weeks) with autologous serum and then transferred onto a collagen matrix. After another week, these composites were transplanted into the sinuses. In group 2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [Ø] = 8 mm) blocks, and cultivated for another 1.5 months. These composites were transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2) months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5 years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone was found in all cases at median densities of 38% (n = 12) in group 1, 32% in group 2A (n = 3), and 25% in group 2B (n = 5). Differences between group 1 and 2B as well as 2A and 2B were statistically significant ( p = 0.025). No adverse effects were seen. All methods described were capable of creating new bone tissue with sufficient stability for successful implant placement.

Adult↗
PubMed2006

Is there a need for autogenous blood donation in orthognathic surgery?

BACKGROUND: The present study sought to determine the frequency of blood transfusion and to evaluate the need for autogenous blood donations in patients undergoing bimaxillary orthognathic surgery. METHODS: According to an inclusion and exclusion protocol, 65 patients were selected for further analysis. Twenty-six patients donated a total of 45 units of autogenous blood; the remaining 39 patients did not. Medical records were reviewed retrospectively. RESULTS: Donors tended to have lower preoperative, intraoperative, and postoperative hemoglobin values, as well as lower hematocrit and leukocyte counts. Only the difference in mean preoperative leukocyte count, however, was statistically significant (donor: 6500/microl versus nondonor: 7400/microl; p = 0.021). The rate of transfusion was 2.5 percent for nondonors and 13 percent for donors of autogenous blood. Six donors had to be transfused a total of 8 units of autogenous blood, whereas only one of 39 nondonors received an allogenic blood transfusion. This difference turned out to be significant according to Fisher's exact test (p = 0.013). None of the donors received allogenic blood transfusion. CONCLUSIONS: In the authors' analysis, preoperative autogenous blood donation appears to be effective in reducing exposure to allogenic blood. Donors of autogenous blood, however, were transfused significantly more often than nondonors were. Neither intraoperative blood loss nor hematological values justify a preoperative donation of autogenous blood on a regular basis.

Adult↗
PubMed2006

CD 14+ cell collection in non-cytokine-stimulated donors with the COM.TEC cell separator.

BACKGROUND: The COM.TEC cell separator (Fresenius Hemocare), equipped with the MNC program (single-stage chamber) and the PBSC-LYM program (dual-stage chamber), was evaluated for CD 14+ cell collection regarding cell yields, collection efficiencies (CEs), and the content of residual cells in harvests. STUDY DESIGN AND METHODS: Twenty-four non-cytokine-stimulated donors underwent 5-L mononuclear cell (MNC) collections on the COM.TEC device to compare both programs. Two software versions (v02.03.05 vs. v 03.00.04) were investigated for optimization of the CD 14+ cell collection process. Blood counts of donors and products were analyzed for CD 14+ cells by flow cytometry and for platelets (PLTs), white blood cells, and red blood cells (RBCs) by a blood cell counter. RESULTS: In 5-L collections, the MNC program resulted in high CEs (83+/- 23%) and yields (1.2 x 10(9)+/- 0.6 x 10(9) per unit) of CD 14+ cells, but the products showed high residual PLTs. The use of a dual-stage chamber in the PBSC-LYM program produced a low content of residual PLTs (0.7 x 10(11) +/- 0.3 x 10(11) per unit) and RBCs but failed to reach a target of 1 x 10(9) CD 14+ cells. Modulated light to stabilize the buffy-coat detection by the interface monitor significantly improved CD 14+ cell enrichment. By use of the PBSC-LYM program, higher centrifuge velocity (1700 rpm [382 x g] vs. 1500 rpm [297 x g]) improved significantly CD 14+ cell yields (0.7 x 10(9) vs. 0.5 x 10(9) cells). CONCLUSION: A pure CD 14+ cell product with low numbers of residual cells was obtained by the PBSC-LYM program, which could be useful for good manufacturing practice-conformed production within closed systems. The MNC program offers the collection of high CD 14+ cell yields with excellent CEs but also high residual PLT counts.

Blood Donors↗
PubMed2006

Washing platelets with new additive solutions: aspects on the in vitro quality after 48 hours of storage.

BACKGROUND: Rare clinical conditions cause the need for washed platelet (PLT) concentrates (PCs). Saline-washed PCs can only be stored shortly, however, owing to lack of substrates for PLT metabolism. New PLT additive solutions (PASs) contain such substrates and might be used alternatively. The in vitro quality of apheresis PCs washed with Composol-PS or modified PAS-III (PAS-IIIM) stored up to 48 hours after wash was compared. STUDY DESIGN AND METHODS: Twelve blood donors underwent two apheresis procedures (A and B) collecting 6.0 x 10(11) PLTs in 500 mL of plasma with a least 2 weeks in between. The PCs collected by Apheresis A were stored for 3 days and then split in two equal units before washing with Composol-PS or PAS-IIIM. The PCs collected by Apheresis B were split after collection. One unit was released for transfusion and 1 unit was stored unwashed up to Day 6 and used as reference unit. In vitro testing was performed before and after washing as well as 24 and 48 hours after wash. RESULTS: After 48 hours of postwash storage, the units washed with either PAS showed acceptable results for hypotonic shock response (HSR), P-selectin expression, and pH, whereas PLT aggregability was significantly impaired. Throughout the storage, unwashed units showed better in vitro quality. HSR and P-selectin expression were similar before and immediately after the washing procedure. CONCLUSION: Based on these in vitro results, 48-hour postwash storage of washed PCs with the two PASs seems to be feasible. In vivo recovery studies, however, must confirm this finding in the future.

Blood Platelets↗
PubMed2006

Platelet function in variable platelet split products intended for neonatal transfusion.

BACKGROUND: Only a few systematic studies have examined the effect of variable produced small platelet (PLT) aliquots on PLT function before transfusion to neonates. Although neonatal transfusion could be critical, no standardization of production or systematic quality controls have been introduced so far. STUDY DESIGN AND METHODS: PLT split products were prepared in three different ways (30- or 60-mL bag, syringe aliquot) at different times from the parent unit (Days 1-4) and stored for 2 or 4 hours. The measures of PLT function include pH, lactate, P-selectin expression, and cytokines (beta-thromboglobulin [beta-TG], PLT-derived growth factor AB [PDGF-AB]). Additionally, syringe passage (0.5 mL/min) was assessed. RESULTS: High product variability of PLT content was found (40% deviation of PLT content from programmed target, 13%-19% PLT loss by product distribution), which resulted in PLT concentrations of split units between 0.94 x 10(9) and 1.66 x 10(9) PLTs per mL. Different gas transfer rates (pCO2) of PLT containers caused different pH values of the product (Trima 7.47 +/- 0.09 vs. COM.TEC 7.33 +/- 0.08; p < 0.0001), but acceptable results of PLT metabolism were found in all split units (minimum pH, 7.09; maximum lactate content, 13.1 mmol/L). P-selectin expression on PLTs increased by factor of 2 in the parent units stored for 4 days (16.9 +/- 8.6% 32.2 +/- 13.4%; p = 0.02). After Day 3, beta-TG and PDGF-AB increased by twofold. PLTs stored during passage for 100 minutes in syringes dropped pO(2) by 50 percent and caused 15 percent higher lactate levels. CONCLUSION: High variability of PLT content in split units requires at least additional PLT counts before transfusion in critical preterm or neonatal infants.

Adult↗
PubMed2006

A pilot study of continuous ambulatory monitoring of blood pressure in repeated preoperative autologous blood donation.

BACKGROUND: The aim of this study was to investigate the occurrence of hypotension in the 24-hour period after preoperative autologous blood donation (PABD) in patients with and without hypertension. STUDY DESIGN AND METHODS: In 20 patients, 24-hour ambulatory blood pressure monitoring (ABPM) was performed before PABD was started and on every donation day in two repeated phlebotomies. RESULTS: Seven patients had no hypertension and 11 patients had hypertension. In 2 additional patients, hypertension was diagnosed during the study. Overall, the mean systolic BP (SBP) decreased from 131+/-15 mmHg before donation to 128+/-13 and 127+/-10 mmHg after Donations 1 and 2; the corresponding values for the diastolic BP (DBP) were 77+/-9, 75+/-9, and 73+/-7 mmHg, both without significant differences between the groups with and without hypertension. In single patients, substantial decreases of BP occurred, especially during the night. Two patients with and 2 without hypertension showed a nightly decrease in SBP and DBP of more than 10 percent (in 1 of these patients, more than 20%). Concerning diurnal BP variability, 1 patient with and 1 without hypertension, the latter showing a nightly decrease of SBP and DBP of more than 10 percent, also changed to the pattern of a nightly "extreme dipper" after PABD. CONCLUSION: In 25 percent of the patients, changes of BP were observed during the 24-hour period after PABD, especially during the night, which are known to be associated with an increased risk of cerebral or myocardial ischemia. Whether those changes of BP lead to major morbidity or mortality requires further investigation.

Adult↗
PubMed2006

Impact of different hold time before addition of platelet additive solution on the in vitro quality of apheresis platelets.

BACKGROUND: The quality of platelets (PLTs) stored in PLT additive solution (PAS) is dependent on the type and proportion of the used PAS. No data are available as to whether a different hold time before the addition of PAS to hyperconcentrated PLT suspensions has an impact on PLT quality. The in vitro quality between single-donor PLT concentrates was compared with two different hold times with two PASs. STUDY DESIGN AND METHODS: On two occasions, 6x10(11) PLTs in 150 mL of plasma were collected from 20 blood donors. The units were split into two equal parts, and 140 mL of PAS-II or PAS-IIIM (randomized sequence) was added after 2 or 8 hours resulting in a PAS proportion of 65 percent. On Days 1, 5, and 7, glucose and lactate concentration, pH value, PLTs' P-selectin expression, response to hypotonic shock, and release of transforming growth factor-beta1 were determined. RESULTS: On all days, the lactate concentrations were higher and pH values were lower in units with an 8-hour hold time, whereas the results of in vitro tests relating to the in vivo viability and activation of PLTs were similar for both groups. PAS-IIIM-stored PLTs showed a lower glycolytic activity and better results in all performed in vitro tests than PAS-II-stored PLTs. CONCLUSIONS: Although the metabolism of glucose was enhanced during hold time, the differences between both hold time groups are not meaningful from a biological viewpoint. Therefore, an 8-hour hold time is feasible. PLT storage in PAS-IIIM results in a PLT in vitro quality superior to that of PLTs stored in PAS-II.

Blood Platelets↗
PubMed2006

Lack of beneficial effects of platelet-rich plasma on sinus augmentation using a fluorohydroxyapatite or autogenous bone: an explorative study.

BACKGROUND: Maxillary sinus augmentation is frequently necessary before placement of dental implants in the posterior maxilla. Besides autogenous bone graft, various bone substitutes have been used, with favourable results. Although platelet-rich plasma (PRP) has been used in the field of oral and maxillofacial surgery for years, its beneficial effects on osseous regeneration still remain unclear. The aim of this study was to evaluate the short and long time effects of PRP on single-stage sinus augmentation using autogenous bone or a fluorohydroxyapatite (Algipore) in a randomized prospective animal study. METHODS: After extraction of maxillary premolars of sixteen minipigs, the wounds were allowed to heal for 2 months. Then, sinus augmentations were performed bilaterally using one of the following grafting materials: autogenous bone and Algipore with or without PRP. Three dental implants (Ankylos) were installed in each sinus simultaneously. Four animals were euthanized at each period of observation (1, 2, 8 and 12 months). Implant-bearing specimens were sectioned bucco-lingually along the long axis of implants and undecalcified ground specimens were prepared. The bone-implant-contact (BIC) was measured by means of microradiographic examination. For histological evaluation, the specimens were stained with toluidin blue, and the percentage of the newly formed bone and the remaining bone substitute were evaluated. RESULTS: The grafting materials chosen showed increasing levels of BIC and newly formed bone throughout the period of observation in both PRP and non-PRP groups. Adding PRP resulted in lower BIC and newly formed bone compared with autogenous bone grafts or Algipore alone. However, a statistical significance was not found. The percentages of the remaining bone substitute in both the PRP and non-PRP groups were closely comparable in all observation periods. CONCLUSIONS: The application of PRP could not reveal significant beneficial effects on the BIC, the percentage of the newly formed bone and the remaining bone substitute in this study.

Animals↗
PubMed2006

The ATGL gene is associated with free fatty acids, triglycerides, and type 2 diabetes.

Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.

Adult↗
PubMed2006

Prospective evaluation of hepatitis B, C and HIV infections as possible sequelae of antineoplastic treatment in paediatric sarcoma patients: a report from the Late Effects Surveillance System.

Cancer therapy and supportive measures entail the risk of infection with hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV). The objective of this analysis was to establish the incidence of infections with these viruses during antineoplastic treatment in our paediatric sarcoma patients, who are being followed-up within the Late Effects Surveillance System (LESS), which prospectively registers sequelae of therapy for Ewing's-, soft tissue- and osteosarcoma in patients treated in Germany, Austria and Switzerland within the trials EICESS-92/EURO-E.W.I.N.G.-99, CWS-96/CWS-2002P and COSS-96. We studied 264 eligible relapse-free paediatric patients [median age at diagnosis 14.3 (IQR 11.1-16.4) years], treated from January 7, 1998 until April 24, 2004. According to the LESS protocol, serological examinations for HBV, HCV and HIV were scheduled 4 weeks and 6 months after cessation of antineoplastic treatment. The median follow-up was 20.6 (IQR 12.4-26) months. None of the patients was reported to have acquired HBV, HCV or HIV during antineoplastic treatment. Blood donor screening and prophylactic measures employed in Germany, Austria and Switzerland to prevent infections of cancer patients with HBV, HCV and HIV seem to be very effective, having fully prevented new infections in this large cohort of paediatric sarcoma patients.

Adolescent↗