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Biomedical subjects

G Mayer

Publications and source records attributed to G Mayer.

At least 91 records · Page 5Linked to original sources
PubMed1999

Aptamers as tools in molecular biology and immunology.

We have listed and described recent promising developments in the field of aptamer research. The properties and the application potential of aptamers propose an exciting future for aptamers either in the clinic or as research tools for various purposes. We have reviewed exciting examples in which the SELEX technology was applied to obtain promising tools that may help to facilitate our understanding of biological processes and to interfere at distinct points in signal transduction cascades. High affinities and specificities of aptamer/target-interactions can now routinely be achieved. Furthermore, a wide spectrum of chemical modifications of nucleotides is known which greatly increase the stability of RNA molecules in biological materials, considerably enhancing their application potential. The aptamer technology shows that the combination of organic synthesis and molecular biology can contribute to interesting and promising new drug leads, which may very soon find their way into daily clinical practice or onto the laboratory benches of many researchers in the life sciences.

Allergy and Immunology↗
PubMed1999

Effect of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature.

Multiple myeloma with IgG-lambda monoclonal gammopathy and severe renal impairment with light-chain deposit disease was diagnosed in a 51-year-old man. Following conventional therapy with VAD (vincristine, adriamycin, dexamethasone) a partial remission was achieved. Peripheral blood stem cells (PBSC) were then collected following mobilization with cyclophosphamide and recombinant human granulocyte colony-stimulating factor and enriched for CD34-positive cells by immunoaffinity column. Fourteen months after diagnosis high-dose melphalan was given, followed by infusion of CD34-positive PBSC. Aside from mild oral mucositis and trigonitis, high-dose therapy was tolerated well. After he underwent PBSC transplantation his renal function improved, and the patient has been in in continuous complete remission for 1 year. Thus, high-dose chemotherapy can be safely administered to patients with multiple myeloma and severe renal impairment. Our findings confirm previous reports summarized in the current presentation.

Antineoplastic Agents, Alkylating↗
PubMed1999

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias.

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.

Aged↗
PubMed1999

Post-transplant acute myeloid leukemia (PT-AML).

Acute myeloid leukemia following organ transplantation (PT-AML) is a rare event with only a few published cases in the literature. We present three patients who developed AML (FAB M1, M5, M4) after renal, double lung or liver transplantation. Molecular analysis detected a t(9;11) in one patient and documented the recipient origin of AML in a second patient. All patients were treated with chemotherapy. Immunosuppression was reduced to cyclosporin A (CsA) and prednisone in two patients and to prednisone alone in one patient. Two patients achieved a complete remission (CR), with a remission duration of 4.6 months in one patient, the other patient died from septicemia after 15.2 months in CR. One patient was refractory to chemotherapy and died from septicemia. This report together with the documented cases in the literature suggests that PT-AML (1) develops after a median interval of 5 years after transplantation with variable latency (range, <1-17 years); (2) is heterogeneous with respect to FAB classification; (3) shows chromosomal and molecular changes typical of therapy-related AML (t-AML: -7, +8, 11q23, inv16, t(15;17)); (4) standard chemotherapy is feasible after reduction of immunosuppression and produces a CR rate of 56% with a median remission duration of 4.6 months and an overall survival of 2.6 months; (5) the major complications are early death (25%), gram-negative septicemia, progressive disease or relapse. This review provides diagnostic and therapeutic experiences and guidelines for the management of this increasing group of post-transplant patients.

Acute Disease↗
PubMed1999

Enhancing of anti-viral activity against HIV-1 by stimulation of CD8+ T cells with thymic peptides.

HIV-1 can be neutralized by soluble factors produced and secreted by activated CD8+ T cells. Production of such anti-viral CD8 factors (including chemokines) can be induced with IL-2 or phytohaemagglutinin (PHA). In addition to PHA or IL-2, we have co-stimulated CD8+ T cells with PHA/IL-2 and a mixture of thymic peptides (TP) of molecular weights below 10 kD. For the activation, CD8+ T cells were purified from peripheral blood mononuclear cells of HIV-1- individuals and any resultant anti-viral activity was monitored using an HIV-1 neutralization assay. Using HIV-1 isolates highly resistant to chemokine inhibition we detected significantly higher levels of HIV-1 neutralizing activity in CD8+ T cell culture supernatants which had been co-activated with TP. When the TP-induced anti-viral activity was monitored, neutralization of both non-syncytia-inducing (NSI) and syncytia-inducing (SI) patient isolates was enhanced by 38% (NSI, PHA +/- TP), 66% (SI, PHA +/- TP), 28% (NSI, IL-2 +/- TP), and 57% (SI, IL-2 +/- TP) compared with the anti-viral activity present in supernatants from CD8+ T cell cultures stimulated only with PHA or IL-2. Peptide sequence analysis of purified TP showed that the TP mixture predominantly contains peptides with homology to human histone and collagen sequences. Our data demonstrate that CD8+ T cells are additionally activated by a mixture of TP. In this way, the production of HIV-1 neutralizing CD8 factors can be enhanced.

Adjuvants, Immunologic↗
PubMed1999

Lipid-lowering therapy in membranous nephropathy.

Membranous nephropathy (MN) is a very common cause of nephrotic syndrome in adults, and lipid abnormalities are, therefore, frequently found in these subjects. Although efficient lipid-lowering therapy is available, almost nothing is known about the contribution of hyperlipidemia in the pathogenesis of progressive renal failure in MN. Studies in an experimental animal model of human MN, Heymann nephritis, have shown that lipids play an essential role in the pathogenesis of proteinuria. Local production of reactive oxygen species after subepithelial immune complex deposition leads to the formation of lipid peroxidation (LPO) adducts, which ultimately alter the composition of the glomerular basement membrane. As the magnitude of urinary protein excretion is associated with the long-term prognosis, a normalization of glomerular permselective properties has been used as a surrogate parameter for the beneficial effects of treatment. Probucol, a drug with LPO inhibitor potential, is able to reduce urinary protein excretion in rats with passive Heymann nephritis. In humans with MN, preliminary data also support this observation. It remains to be determined, however, if this intervention, which does not interfere with immune complex formation, will reduce the number of the patients reaching end-stage renal failure because of MN. In conclusion, lipids may contribute to glomerular injury in MN, as LPO might be an especially important factor, opening the possibility for new therapeutic interventions, thereby avoiding the side-effects of the currently used treatment regimen.

Glomerulonephritis, Membranous↗
PubMed1999

Immunogold signal amplification: Application of the CARD approach to electron microscopy.

Catalyzed reporter deposition (CARD) is a technique that allows amplification of routine immunolabeling in light microscopy. This procedure takes advantage of the horseradish peroxidase (HRP) from an HRP-avidin complex to catalyze the accumulation of reporter-conjugated tyramine (a phenolic compound) onto a surface displaying biotinylated antigen-antibody complexes. The large amount of labeled tyramine deposited allows the detection of an antigenic site with multiple reporter molecules. In this study we modified this amplification protocol to combine it with the immunogold technique for the ultrastructural localization of antigens in electron microscopy. We constructed various tyramide conjugates that permit the combination of this amplification method with a particulate colloidal gold marker. The new probes yield results of high specificity and enhanced intensity. Assessment of the level of resolution of the labeling has demonstrated that, in spite of the amplification, the resolution remains very good. Therefore, once associated, the immunogold and the CARD techniques lead to specific, high-resolution, sensitive and amplified signals that exhibit the advantages of both approaches.(J Histochem Cytochem 47:421-429, 1999)

Amylases↗
PubMed1999

Novel C5-dependent mechanism of neutrophil stimulation by bioincompatible dialyzer membranes.

The objective of the study was to evaluate the contribution of reactive oxygen intermediate formation for receptor modulation on neutrophils by the cellulosic dialyzer membrane cuprophan (CU). In patients dialyzed with CU, CD11b and CD66b upregulation on neutrophils (by 104.3 +/- 37.9% and 85.7 +/- 31.1%, respectively), and a downregulation of L-selectin (by 44.9 +/- 26.9%) was seen, whereas expression of CD11a remained unaltered. Hemodialysis with polysulfone did not bring about major changes in surface receptor expression. In vitro incubation of isolated neutrophils in the presence of serum with hollow fibers of CU or polysulfone showed similar results: Only CU resulted in upregulation of CD11b and CD66b expression (by 65.5 +/- 18.7% and 60.1 +/- 24%) and a decrease in CD62L expression (by 60.6 +/- 18.2%). In contrast to receptor alterations, generation of reactive oxygen intermediate by CU occurred in the absence of serum. Inhibition experiments with soluble complement receptor 1, which produced only partial inhibition of receptor up-/down-regulation, indicated the existence of also other than alternate complement-dependent mechanisms for neutrophil activation. By using C5-depleted serum instead of normal human serum, up-/down-regulation of CD11b, CD62L, and CD66b by CU was dramatically reduced, whereas C3-depleted serum did not produce that effect. C5-deficient serum repleted with purified C5, as well as purified C5 alone, was able to induce receptor modulation by CU comparable to normal human serum. L-Methionine, a specific inhibitor for the oxidative activation of C5, blocked the modulatory effect of CU in assays with purified C5 as well as with serum. As a result, in addition to the alternative pathway of complement, a C5-dependent mechanism probably activated by neutrophil-derived reactive oxygen intermediate leads to receptor modulation and subsequent generation of the well known side effects of bioincompatible dialyzer membranes.

Adult↗
PubMed1999

Apoptosis of tubular epithelial cells in donor kidney biopsies predicts early renal allograft function.

Acute renal failure (ARF) is a serious complication in the early postoperative period after kidney transplantation. In an effort to identify subjects at risk, several donor-, recipient-, and procedure-related factors have been studied. Because no morphologic parameter predictive of delayed graft function has been identified to date, this study was conducted to determine whether the number of apoptotic cells in donor biopsies obtained before engraftment is predictive of the development of posttransplant ARF. Donor biopsies of patients with "biopsy-proven" acute tubular damage but no signs of rejection (n = 23) showed significantly higher counts of apoptotic tubular epithelial cells when compared to patients with immediate transplant function (n = 44) or early rejection (n = 22). In all groups, a significantly higher percentage of apoptotic cells was found in the distal compared to the proximal tubule. The expression of bcl-2 and proliferating cell nuclear antigen was not different among the groups. Late allograft function was not affected by early ARF as serum creatinine values were similar in all three groups after 6 mo. These data suggest that the number of apoptotic renal tubular epithelial cells in donor biopsies before engraftment is predictive of the early postoperative course in patients undergoing kidney transplantation.

Acute Kidney Injury↗
PubMed1999

Application of the green fluorescent protein as a reporter for Ace1-based, two-hybrid studies.

The two-hybrid system in Saccharomyces cerevisiae is a genetic approach for the detection of of protein-protein interactions in vivo. This technology relies on the the activity of separated DNA-binding and transactivation domains of specific transcription factors to reconstitute an active transcription factor complex if interacting proteins are fused to these domains. Interactions are consequently detected through the activity of reporter genes. The two-hybrid technology has been successfully applied for the determination of interactions between numerous proteins of several organisms. Conventional reporter systems, such as the beta-galacatosidase from Escherichia coli, suffer from a variety of drawbacks, including the requirement for external substrates. In this report, we describe an alternative version of the two hybrid system using the combined advantages of the copper-inducible transcription factor Acel together with the yeast metallothionein gene CUP1 and the green fluorescence protein from aquatic invertebrates as reporters. This technique allows the copper-dependent monitoring of protein-protein interactions in living yeast cells.

Carrier Proteins↗
PubMed1999

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy

Acetylcholinesterase↗
PubMed1999

Anemia and carnitine supplementation in hemodialyzed patients.

Carnitine supplementation in hemodialyzed patients was studied in a double-blinded, randomized, controlled trial in order to elucidate the effect of intravenous carnitine on renal anemia in patients treated with recombinant human erythropoietin (rHuEPO). Twenty stable hemodialysis (HD) patients received intravenous L-carnitine after each dialysis session in a dosage of 5 (N = 15) and 25 (N = 5) mg/kg, respectively, together with intravenous iron saccharate (20 mg/HD session) for four months and without iron for a further four months. Twenty patients received placebo instead of carnitine with an identical iron regimen. After a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin levels. At study entry (T0), plasma and red blood cell carnitine levels did not correlate significantly with the rHuEPO requirement. However, plasma free and total carnitine levels showed a significant negative correlation with erythrocyte survival time at T0. After four months of coadministration of intravenous iron and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD patients. In these responders, the weekly rHuEPO dose was decreased significantly by 36.9+/-23.3% (183.7+/-131.7 at T0 vs. 126.6+/-127.9 U/kg/week at T4, P < 0.001). The rHuEPO requirement, however, was unchanged when all carnitine-treated patients were compared between T0 and T4 (T0: 172.0+/-118.0 vs. T4: 152.3+/-118.8 U/kg/week, P = 0.07, NS), but the erythropoietin resistance index decreased significantly in this group (T0: 16.0+/-11.0 vs. T4: 13.6+/-10.5 U/kg/week/g of hemoglobin, P < 0.02). The erythrocyte survival time was measured in five HD patients treated with iron and carnitine at T0 and T4. Two out of these patients were carnitine responders and showed an increase of erythrocyte survival time of 15 and 20%, respectively. After the withdrawal of iron supplementation, the rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated patients during four more months. According to our data, L-carnitine, in addition to iron supplementation, may have an effect on erythropoietin resistance and erythrocyte survival time in HD patients. More than half of our patients, however, showed no benefit. Further studies to identify those HD patients who might have a benefit of carnitine supplementation, as well as studies concerning the optimal dosage, duration, and way of administration of carnitine supplementation and its mechanism of action, are required.

Adult↗
PubMed1998

The StrQ protein encoded in the gene cluster for 5'-hydroxystreptomycin of Streptomyces glaucescens GLA.0 is a alpha-D-glucose-1-phosphate cytidylyltransferase (CDP-D-glucose synthase).

The gene strQ was identified as the last gene of a putative transcription unit, strB1FGHPQ, located in the gene cluster for the production of 5'-hydroxy-streptomycin (OH-Sm) in Streptomyces glaucescens GLA.0. [In contrast, the corresponding operon in the str/sts-gene cluster of the Sm-producer Streptomyces griseus, strB1FGHIK, differs in the two distal genes; Mansouri, K. & Piepersberg, W. (1991) Mol. Gen. Genet. 228, 459-469]. The deduced StrQ protein exhibited similarities to members of the enzyme family of hexose-1-phosphate nucleotidylyltransferases (NDP-hexose synthases or pyrophosphorylases), with the strongest similarity to the subfamily of alpha-D-glucose-1-phosphate cytidylyltransferases (CDP-D-glucose synthases). The StrQ protein was heterologously expressed in Escherichia coli. The purified protein revealed an enzyme activity of that of a CDP-D-glucose synthase and a substrate specificity restricted to CTP and alpha-D-glucose 1-phosphate. The K(m) and Vmax values determined for CTP are 44 microM and 920 microM and for alpha-D-glucose 1-phosphate 195 microM and 1.06 mM, respectively. The CDP-D-glucose synthase activity was also detected in cells of S. glaucescens under the conditions of antibiotic production, but was absent from cells of the streptomycin producer S. griseus N2-3-11. Also, the genomes of several strains of S. griseus did not seem to possess strQ-related genes. In contrast, hybridisation experiments indicated that genes homologous to strQ were probably present in various other actinomycetes producing aminoglycosides. A possible function of the StrQ protein in the OH-Sm biosynthetic pathway of GLA.0 is discussed.

Amino Acid Sequence↗
PubMed1998

Endocrinological and polysomnographic findings in Kleine-Levin syndrome: no evidence for hypothalamic and circadian dysfunction.

Five subjects--four men, ages 17-28, and one woman, age 30--with Kleine-Levin syndrome were investigated during symptomatic (SP) and asymptomatic (ASP) periods. Investigations comprised medical history, MRI, polysomnography, 24-hour hormone profile of human growth hormone, melatonin, TSH, cortisol and FSH (in the woman only) assessed every 2 hours, actimetry, and sleep logs. Medical history confirmed presence of the three symptoms diagnostic of of typical Kleine-Levin syndrome: hypersomnia, excessive food intake, and psychic alteration. MRIs of the brain were normal in all patients. Symptomatic periods were triggered by unspecific events, such as infection, sleep deprivation, and alcohol. Polysomnography revealed low sleep efficiency during SPs, decreased amount of slow-wave sleep, and high frequency of stage shifts, indicating sleep fragmentation. Mean 24-hour growth hormone levels were reduced during the SPs in only two patients. Their hGH peaks were dissociated from slow-wave sleep during attacks and intervals, often occurring during wake time. Twenty-four-hour melatonin levels were increased during the SPs in all patients, but were lower in two patients during the nocturnal sleep period. Cortisol, TSH and FSH did not reveal important differences between attacks and intervals. Except for hGH, all hormones had normal circadian excretion during symptomatic and asymptomatic periods. Amplitude of nocturnal activity as assessed by actimetry was significantly increased in two patients, whereas amplitude of daytime activity was significantly reduced in three patients. Actimetry and sleep logs demonstrated prolonged sleep phases during SPs. Our investigation could confirm changes of sleep structure described in the literature. The neuroendocrinological findings could not confirm decreased hGH and cortisol and increased TSH levels during SPs, as previously reported in single cases by many authors. Endocrinological findings did not support an underlying circadian disorder in KLS.

Adolescent↗