Relevance of the treatment facility for disease-related knowledge of diabetic patients.
Explore the source record for details and available documents.
Diabetes Mellitus, Type 1↗
Biomedical subjects
M Hildebrandt
Publications and source records attributed to M Hildebrandt.
A guardian angel: the involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defence.
Dipeptidyl peptidase IV (DPP IV, also known as CD26; EC 3.4.14.5) is a non-integrin receptor glycoprotein with multiple functions, including cell adhesion, cellular trafficking through the extracellular matrix and co-stimulatory potential during T cell activation. By virtue of its exopeptidase activity, DPP IV plays a key regulatory role in the metabolism of peptide hormones. Based on data emerging from different biomedical specialties, it appears worthwhile to highlight the different facets of DPP IV in nutrition, immune responses and peptide hormone metabolism. The presentation of the complex regulatory circuits in which DPP IV appears to be involved may also serve as a note of caution, in view of attempts to apply selective inhibitors of DPP IV enzymic activity for the treatment of disease, e.g. Type II diabetes.
Animals↗
Detection of germ-cell tumor cells in peripheral blood progenitor cell harvests: impact on clinical outcome.
Our study was conducted to evaluate the impact of tumor cell contamination in peripheral blood progenitor cell (PBPC) harvests on the clinical outcome of patients with germ-cell tumors undergoing high-dose chemotherapy (HDCT) and autologous PBPC reinfusion. Samples of mononuclear cells from progenitor cell harvests of 57 patients with advanced or recurrent germ-cell tumors were retrospectively screened for contaminating tumor cells using immunocytochemical staining for cytokeratin filaments and reverse transcription-PCR (RT-PCR) testing for germ-cell alkaline phosphatase mRNA. The results were correlated to clinical prognostic variables as well as to the overall and event-free survival of these patients. Tumor cell contamination was detected in PBPC harvests of 16 of 57 enrolled patients (28%), and, among these, in 14 of 51 (27%) who underwent HDCT. The presence of contaminating tumor cells as detected by either immunocytochemical staining, RT-PCR, or both was strongly associated with a reduced overall survival (43% versus 71%, P = 0.0037) and event-free survival (0% versus 52%, P = 0.0005) after 1 year. In multivariate analysis, the demonstration of contaminating tumor cells had a higher predictive value for a poor event-free survival than other known prognostic variables. The presence of contaminating tumor cells in PBPC harvests of patients with germ-cell tumors seems to predict a poor overall and event-free survival in patients undergoing HDCT and autologous PBPC reinfusion.
Adult↗
Severe anorexia nervosa associated with osteoporotic-linked femural neck fracture and pulmonary tuberculosis: a case report.
We report a case study of a 38-year-old woman who had been suffering from anorexia nervosa (AN) since the age of 26. Before admittance to our clinic, she weighed 23.8 kg (at a height of 164 cm, 8.8 body mass index [BMI]) but still carried out strenuous physical activities. After good psychotherapeutic response and weight gain (34.4 kg), she accidentally fell and broke her femoral neck-favored as it was by osteoporosis. The X-ray taken before dynamic hip screw implantation coincidentally showed signs of pulmonary tuberculosis (TB), which could then be proven by computed tomography (CT) scans and cultures from a bronchoscopy. Other than lack of appetite and loss of weight, which we attributed to AN, there were no other clinical or biochemical indicators which could have pointed to an earlier TB diagnosis. As a result, the need for screening procedures is discussed. The manifestation of TB during the first weight gain after 12 years of severe malnutrition, during which there were no serious infections, seems to endorse former observations that AN patients appear to be "resistant" to some extent against infectious diseases, a "protection" which may be lost with convalescence and weight gain.
Adult↗
Dissociative effects of alcohol on recollective experience.
This article reports a study comparing the effects of a single dose of alcohol with a matched placebo drink on recognition memory with and without conscious recollection. A double-blind, cross-over design was used with healthy volunteers who were all social drinkers. Processing depth at study was manipulated using generate versus read instructions. Conscious recollection at test was assessed using the remember-know-guess paradigm (Gardiner, 1988; Tulving, 1985). Alcohol significantly reduced conscious recollection (remember responses) but had no effect on recognition in the absence of conscious recollection (know responses). False alarms rates were low and unaffected by alcohol. Previous findings that generation effects are found only for remember responses were closely replicated. A further dissociation of the generation effect occurred between treatments in that deeper processing at study facilitated recognition on placebo but not on alcohol. That both alcohol and depth of processing produce dissociative effects on recollective experience provides further evidence that remembering and knowing reflect distinct memory systems.
Adult↗
Alterations in expression and in serum activity of dipeptidyl peptidase IV (DPP IV, CD26) in patients with hyporectic eating disorders.
The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.
Anorexia Nervosa↗
Analysis of CD34-expressing cells in clinical practice.
The flow cytometric determination of haemopoietic cells defined as CD34-expressing cells has greatly added to the improvement of the management of harvesting circulating haemopoietic cells for subsequent autologous reinfusion in the setting of high-dose chemo/(radio)-therapy. Additionally, this flow cytometric determination has replaced, in some institutions, the in-vitro culture test for CFU-GM as the measure to estimate the haemopoietic potential of the cells to be reinfused/transplanted.
Antigens, CD34↗
Monitoring of tumor cell purging after highly efficient immunomagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: comparison of immunocytochemical tumor cell staining and reverse transcriptase-polymerase chain reaction.
We studied the efficiency of indirect tumor cell purging via enrichment of CD34+ hematopoietic progenitor cells from leukapheresis products (LP) in breast cancer patients based on immunomagnetic selection of CD34+ cells. Detection of tumor cells was made by immunocytochemical staining. In addition, we evaluated the capacity of cytokeratin 19 (CK19)- and a novel epidermal growth factor receptor (EGF-R)-specific reverse transcriptase-polymerase chain reaction (RT-PCR) for monitoring tumor cell depletion. LP from 13 breast cancer patients were analyzed. Twenty-three CD34 selection procedures were performed. A median of 1.4 x 10(10) total nucleated cells ([TNC] range, 0.88 to 3.5 x 10(10)) with a median CD34 purity of 2.5% (range, 0.4% to 6.3%) were entered into the selection procedure. Immunomagnetic CD34 enrichment resulted in a median purity of 83.3% (range, 45% to 95.4%) and a median recovery of 73.2% (range, 22% to 95%). Retransfusion of CD34-selected cells after high-dose chemotherapy resulted in a rapid and sustained hematologic recovery, reaching an absolute neutrophil count of 500/microL at day +10 and platelet count of 20,000/microL at day +11. Tumor cell depletion was quantified by immunocytochemical detection of CK19-positive cells. By this method, a median tumor cell depletion of 1.9 log (range, 0.7 to > 3 log) could be demonstrated. Immunocytochemical detection of tumor cells was more sensitive than RT-PCR, yielding positive results in 81% of LP (17 to 21) versus 58% positive LP (10 of 17). However, EGF-R-based RT-PCR was much more sensitive than CK19-based RT-PCR (10 of 17 v 1 of 17). Despite highly efficient CD34 selection, tumor cells were still detectable after CD34 enrichment using immunocytochemistry and EGF-R-specific RT-PCR. Thus, this novel EGF-R-specific RT-PCR appears to be of value as an additional method to detect contaminating breast cancer cells within LP.
Adult↗
Reverse transcriptase-polymerase chain reaction (RT-PCR)-controlled immunomagnetic purging of breast cancer cells using the magnetic cell separation (MACS) system: a sensitive method for monitoring purging efficiency.
A modified reverse transcriptase-polymerase chain reaction (RT-PCR) technique was established with the aim of monitoring the tumor cell contamination in peripheral blood stem cells harvested from breast cancer patients. In an experimental approach, single cell suspensions of different breast cancer cell lines were mixed to normal peripheral blood mononuclear cells in order to 1) determine the sensitivity of tumor cell detection within PBMC and 2) compare polymerase chain reaction in its capacity of monitoring the efficiency of immunomagnetic purging using the magnetic cell separation (MACS) system to immunocytochemical staining. Several target sequences were assessed for their indicative potential and specificity allowing the detection of breast cancer cells by RT-PCR. Among the sequences evaluated, epithelial growth factor receptor (EGF-R) mRNA and Cytokeratin 19 mRNA were shown to be highly specific and sensitive markers for the detection of breast cancer cells within normal peripheral blood mononuclear cells and for the evaluation of the efficiency in immunomagnetic purging. In addition, we were able to show that the MACS is a potent and efficient tool for the selection of tumor cells from peripheral blood mononuclear cells, thus establishing its value for clinical scale immunomagnetic purging.
Breast Neoplasms↗
Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma.
UNLABELLED: Increased glycolysis is a characteristic metabolic feature of a malignant transformed phenotype. In cultured cells transformed by viruses or activated oncogenes, enhanced glycolytic metabolism is mediated by the overexpression of glucose transporter 1 (Glut-1) and key regulatory glycolytic enzymes. Whether increased glucose metabolism in solid human malignant tumors is related to the overexpression of key regulatory proteins of glucose metabolism is presently unknown. We thus studied the expression of Glut-1 and glucose uptake, assessed with 2-fluorodeoxyglucose (FDG) and PET in human pancreatic carcinoma (PC) and chronic mass-forming pancreatitis (MFP). METHODS: Glucose uptake was measured in the fasting state with FDG and PET in 12 patients with PC and 15 patients with MFP. The standardized uptake value (SUV) of FDG was determined as a global quantitative measure of tissue glucose utilization in cancer tissue or MFP. The expression of Glut-1 and Glut-4 was analyzed from operatively removed cancer or MFP tissue by Northern analysis or semiquantitative reverse transcriptase-polymerase chain reaction. The count ratio of Glut-1 to Glut-4 transcripts was used as an indicator of selective Glut-1 up-regulation. RESULTS: The SUVs of FDG in patients with cancer and MFP were 2.98 +/- 1.23 and 1.25 +/- 0.51 (p < 0.01), respectively. Northern analysis showed intense Glut-1 expression in four of five patients with cancer but not in any of the five patients with MFP that were tested. In PC, Glut-1 and Glut-4 transcripts were found in five of five and three of 10 patients, respectively, using reverse transcriptase-polymerase chain reaction, whereas in MFP, Glut-1 was detected in one of five and Glut-4 was detected in all five patients. The Glut-1-to-Glut-4 transcript ratios were 6.17 +/- 1.27 in patients with cancer and 0.42 +/- 0.12 in patients with MFP. The mean Glut-1 concentration in eight patients with cancer was 1.71 nmol of Glut-1 mRNA/microg of mRNA (range, 0.0446-9.43) and 0.15 (range, 0-1.55) (p < 0.05) in 13 patients with MFP. CONCLUSION: The concomitant enhancement of glucose utilization and selective overexpression of Glut-1 mRNA in pancreatic cancer but not in MFP suggested constitutive activation of Glut-1 gene or decreased degradation of Glut-1 mRNA in human pancreatic cancer. These findings may imply a potential for the early detection of pancreatic cancer with FDG and PET and identify new targets for anticancer therapy.
Adult↗
[Prerequisites for diagnostic use of antisense oligonucleotides in nuclear medicine].
A new promising perspective in nuclear medicine is the use of radiolabeled antisense oligonucleotides as diagnostic markers. Especially for cancer diagnostics, a quantitative accumulation of antisense probes which are directed against abundantly expressed oncogene mRNAs seems to be reasonable. However, the development of this strategy still requires an optimization of several parameters: (i) rapid and efficient radiolabeling methods, (ii) a fast penetration of the probe into the target tissue, (iii) a fast internalization into the tumor cell, (iv) an oligonucleotide/mRNA hybrid formation with high specificity, and (v) a high stability of the hybrid against intracellular nucleases.
Humans↗
A human NDP-kinase B specifically binds single-stranded poly-pyrimidine sequences.
Recently, a DNA binding protein 'PUF' was purified that binds to a poly-pyrimidine rich element in the human c-myc promoter. Cloning of the corresponding gene surprisingly identified this putative transcription factor as isoform B of the enzyme nucleoside diphosphate kinase (NDPK-B) [Postel et al. (1993) Science, 261, 478-480], the product of the potential metastasis suppressor gene nm23-H2. Using different recombinant NDP kinases, we demonstrate by electrophoretic mobility shift analysis (EMSA) that the NDP kinase DNA binding properties are predominantly observed with human isoform B. Unlike typical DNA binding proteins that are involved in transcriptional regulation, binding occurs to single-stranded DNA rather than to a double-stranded oligonucleotide. As a consequence, complexes of single-stranded DNA and NDPK-B are generated from double-stranded oligonucleotide hybrids in an ATP independent manner. In addition to the c-myc element, NDPK-B is binding in vitro to a variety of poly-pyrimidine rich sequences including dC or dT homo-oligomers, (CT)n dinucleotide repeats, the initiator region of the Adenovirus major late promoter and even poly-pyrimidine rich RNAs. The possible consequences of these findings in understanding the multiple roles of NDP kinase are discussed.
Base Sequence↗
Overexpression of wild-type and mutant NDP kinase in Dictyostelium discoideum.
Nucleoside diphosphate (NDP) kinase has a central role in the synthesis of (deoxy-)trinucleotides. In addition, mutations in the gene encoding NDP kinase have been shown to have important consequences for Drosophila development and mammalian tumorogenesis. We have overexpressed, in Dictyostelium discoideum, a genomic clone encoding the enzyme NDP kinase. The concomitant increase in the levels of RNA and enzyme activity identifies a 5' non-coding genomic region of 0.9 kb as being the complete promoter region. Overexpression of wild-type NDP kinase has no effect on development. This is also true for an inactive mutant H122C that does not have a dominant inhibitor effect. Overexpression of the P105G mutant NDP kinase, which is known to be affected in its stability in vitro, only leads to a small increase in total NDP-kinase activity. Thermal and chemical denaturation experiments demonstrate the formation of hexameric hybrids between wild-type and mutant monomers.
Animals↗
Nucleoside diphosphate kinase: an old enzyme with new functions?
Explore the source record for details and available documents.
Amino Acid Sequence↗
Developmental regulation of antisense-mediated gene silencing in Dictyostelium.
In Dictyostelium, the expression of antisense transcripts has been successfully used to reduce or eliminate gene expression. In most cases this occurs on the level of RNA stability resulting in a loss of both sense and antisense transcript accumulation. We here show that the antisense effect is regulated during the developmental cycle, i.e., in certain developmental stages and under certain developmental conditions, complementary RNAs appear not to interact with each other, resulting in a failure to abolish expression of the gene of interest. We find that this is not only the case with artificially introduced antisense constructs but also with the endogenous, antisense-regulated PSV-A gene. Our data demonstrate that antisense-mediated gene silencing is conferred by a biochemical machinery that is subject to regulation in vivo. The results provide a basis to better understand this machinery and to dissect the components. They may also explain the failure of some antisense experiments in Dictyostelium and possibly in other organisms.
Animals↗
[Interference versus low frequency. A comparison of 2 methods of electric muscle stimulation].
The purpose of this study was to determine whether inferential or low-frequency stimulation can produce a stronger and less painful contraction of the quadriceps femoris muscle in 20 healthy subjects. Both currents used a pulse rate of 50 Hz. The perceived discomfort experienced with each type of electrical stimulation was quantified by the use of a visual analogue scale. An isokinetic dynamometer (Cybex) was used to assess peak torque. Paired t-test demonstrated that inferential stimulation was perceived to be significantly less uncomfortable than low-frequency stimulation and that inferential stimulation produced a significantly greater peak torque of muscle contraction than low-frequency stimulation. This study indicates that inferential stimulation can produce an electrically induced muscle contraction which is stronger and less unpleasant than low-frequency stimulation.
Adult↗
Differential antisense transcription from the Dictyostelium EB4 gene locus: implications on antisense-mediated regulation of mRNA stability.
The 2.2 kb mRNA of the Dictyostelium discoideum prespore gene EB4-PSV is constitutively transcribed during growth and development, but the message is only accumulated when cells form aggregates and establish the prespore-prestalk pattern. Disruption of the pattern by mechanical disaggregation results in a rapid loss of the mRNA, while transcription remains nearly unchanged. In early development and after disaggregation, when the mRNA is unstable, a 1.8 kb antisense transcript originating from the same gene locus is detected. This RNA has apparently no coding capacity and is transcriptionally regulated by a promoter located within the translated region of the gene. Excess transcription of antisense RNA in vegetative cells and after disaggregation suggests its involvement in the control of mRNA stability. In agreement with this assumption, the inhibition of RNA synthesis during disaggregation prevents destabilization of the mRNA. This stability regulation of an endogenous mRNA is reminiscent of the loss of specific mRNAs in cells transformed with antisense constructs.
Animals↗
Mechanisms of gene regulation by endogenous and artificially introduced antisense RNA.
Explore the source record for details and available documents.
Animals↗