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Biomedical subjects

J Dittmann

Publications and source records attributed to J Dittmann.

At least 19 recordsLinked to original sources
PubMed2005

Metallothionein biology in the ageing and neurodegenerative brain.

In recent years metallothionein (MT) biology has moved from investigation of its ability to protect against environmental heavy metals to a wider appreciation of its role in responding to cellular stress, whether as a consequence of normal function, or following injury and disease. This is exemplified by recent investigation of MT in the mammalian brain where plausible roles for MT action have been described, including zinc metabolism, free radical scavenging, and protection and regeneration following neurological injury. Along with other laboratories we have used several models of central nervous system (CNS) injury to investigate possible parallels between injury-dependent changes in MT expression and those observed in the ageing and/or degenerating brain. Therefore, this brief review aims to summarise existing information on MT expression during CNS ageing, and to examine the possible involvement of this protein in the course of human neurodegenerative disease, as exemplified by Alzheimer's disease.

Aging↗
PubMed2001

All-trans retinoic acid regulates proliferation, migration, differentiation, and extracellular matrix turnover of human arterial smooth muscle cells.

OBJECTIVE: The vitamin-A derivative all-trans retinoic acid (atRA) is a potent regulator of cell growth, differentiation, and matrix formation of various cell types and plays an important role in embryogenesis. However, sparse data are available about its effects on human vessel diseases. Thus, we studied the effects of atRA on human arterial smooth muscle cell (haSMC) and endothelial cell (haEC) proliferation, migration, differentiation and extracellular matrix (ECM) turnover in mono- and transfilter cocultures. METHODS: Effects of atRA on human arterial cells in monocultures were determined using cell counting assays, BrdU-ELISA and MTT-tests. In transfilter cocultures haSMC-growth was studied under the stimulatory effect of proliferating haEC. Using Northern blot analysis, effects of atRA on mRNA expression of ECM-proteins were examined while protein expression and activity of matrix metalloproteinases were determined by Western blotting and zymography. RESULTS: atRA caused a dose dependent inhibition of haSMC-growth in monocultures (IC(50) at 0.022 microM) whereas haEC-growth was inhibited less potently (IC(50) at 97 microM). In addition, proliferation and migration of haSMC through a porous membrane were inhibited dose dependently by micromolar atRA-doses after non-stop and single dose application of atRA on the endothelial side of the complex transfilter coculture system. Immunostainings and Northern blotting demonstrated an enhanced alpha-smooth muscle actin and heavy chain myosin expression in haSMC after atRA-treatment. Whereas mRNA-expression of the glycoproteins thrombospondin-1 and fibronectin were decreased, collagen-1 mRNA expression was even slightly stimulated. Transcription of biglycan and TGF-beta1 were not influenced in a specific manner. Finally, protein expression and activity of the matrix metalloproteinases MMP-2 and MMP-9 were inhibited significantly by atRA. CONCLUSIONS: atRA was found to be a potent inhibitor of both haSMC-proliferation and -migration, even in coculture with haEC releasing growth factors. In addition, redifferentiation, ECM synthesis and ECM degradation were regulated by atRA which also influence haSMC migration and intima formation. Thus, atRA-treatment seems to be a promising strategy for the inhibition of processes involved both in atherosclerosis and restenosis.

Arteries↗
PubMed1999

Impact of various glycosaminoglycans upon cAMP-dependent protein kinase.

The physiological effects of the second messenger cAMP are displayed by cAMP-dependent protein kinase-medicated phosphorylation of specific target proteins which in turn control diverse cellular functions. We have determined this enzyme substrate phosphorylation in the presence of various glycosaminoglycans using a cAMP-dependent protein kinase isolated from rat liver. The results indicate that sulfated and unsulfated polysaccharides are able to inhibit phosphorylation of histone type IIa catalysed by cAMP-dependent protein kinase. Based on their impact upon substrate phosphorylation, glycosaminoglycans can be divided into three groups: group I with the highest inhibitory effect: dermatan sulfate and heparan sulfate; group II: chondroitin 4-sulfate and group III with the lowest inhibitory effect: chondroitin 6-sulfate, keratan sulfate and hyaluronic acid.

Animals↗
PubMed1999

[Biochemical efficacy of homeopathic and electronic preparations of D8 potassium cyanate].

INTRODUCTION: The oxidative degradation of urate to allantoin and CO2 is catalyzed by the enzyme uricase. Its activity was determined in the presence of two potassium cyanatum preparations in the dilution step D8, which differed by the method of preparation. While variant 1 (homoeopathic D8) was prepared homoeopathically, variant 2 (electronic D8) was produced electronically. OBJECTIVE: The target of these studies was to investigate the impact of homoeopathic and electronic D8 on the catalytic activity of uricase. METHODS: In the presence of these tow D8 variants, the enzymic degradation of urate was determined by a spectrophotometric assay over a period of 10 minutes. RESULTS: 1. In the presence of homoeopathic D8 a stimulation of enzyme activity was detected. 2. In the case of electronic D8 neither a stimulation nor an inhibition of enzyme-catalyzed urate degradation was observed. 3. The differences in the effect of homoeopathic and electronic D8 on uricase were found to be statistically relevant. CONCLUSIONS: With the help of a cell-free system, such as uricase, it is possible to detect differing effects of homoeopathically and electronically prepared D8. In contrast to the electronic D8, the homoeopathic D8 is capable of modulating the enzyme activity. This observation leads to the assumption that homoeopathically prepared drugs are superior in their therapeutical efficiency to electronically produced drugs. However, the interpretation would be allowed, too, that the cell-free system used in this study, which has been isolated from an organism, is no longer in a position to react to an electronically prepared potency.

Allantoin↗
PubMed1998

Inhibition of adenylate cyclase of rat hepatic membranes by glycosaminoglycans.

Glycosaminoglycans are long non-branched polysaccharides composed of repeating disaccharide units. In a previous in vitro study we have shown that such molecules are able to modulate substrate phosphorylation catalyzed by cAMP-dependent protein kinase. Here, we investigate the impact of glycosaminoglycans, such as heparan sulfate, dermatan sulfate, chondroitin 4- and 6-sulfate, keratan sulfate and hyaluronic acid upon adenylate cyclase, which directly regulates cAMP-dependent protein kinase activity via cAMP synthesis. In rat liver plasma membrane preparation we have determined forskolin- and guanosine-5'-beta, gamma-imidotriphosphate-induced cAMP formation catalyzed by adenylate cyclase in the presence of increasing concentrations of glycosaminoglycans. The results indicate that glycosaminoglycans strongly influence enzymic conversion of ATP into cAMP. The highest reduction of adenylate cyclase activity is observed in the presence of dermatan sulfate and heparan sulfate. Moreover, the inhibitory effect of these two glycosaminoglycans is higher when guanosine-5'-beta, gamma-imidotriphosphate, instead of forskolin, is used as stimulator of adenylate cyclase. Further characterization of enzyme inhibition mediated by dermatan sulfate shows that this molecule exerts an inhibitory effect of mixed type.

Adenosine Triphosphate↗
PubMed1998

Zur Eigenheit von homöopathischen Arzneimitteln und ihrer Wirkung aus naturwissenschaftlicher Sicht.

Characteristics and Efficiency of Homoeopathics from a Scientific Point of View 1. This work aims at the presentation of the specific peculiarities of homoeopathics as physics see it and at the explanation of their display of action by application of biochemical methods. 2. Physical methods are considered to be adequate for the investigation of specific peculiarities of homoeopathic potencies. For logical reasons these methods have to be of theoretical nature for the present. In substance basic assumptions of the potentisation procedure are linked to the demand for necessary qualities which a Therapeutically Active Ingredient (= TAI) of homoeopathic potencies has to have. A theoretical model is proposed which should enable the link between potentisation and the TAI by working out learning processes for the transmission of the TAI. 3. By use of methods of biochemistry it is rendered possible to investigate the efficiency of homoeopathics. From the results of in vivo and in vitro trials a model for their display of action is evolved.

Journal Article↗
PubMed1997

Frequency and causes of refractoriness in multiply transfused patients.

The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20,000/microliters, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components.

Antigens, Human Platelet↗
PubMed1997

Modulation of cAMP-dependent protein kinase by derivatives of chondroitin sulfate.

Here, we report investigations about the direct effect of glycosaminoglycans, such as dermatan sulfate, chondroitin 4- and 6-sulfate upon cAMP-dependent protein kinase activity. The results indicate that glycosaminoglycans strongly influence the phosphorylation activity of this enzyme against histone type IIa and [Val6, Ala7]-kemptide. While chondroitin 4-sulfate and dermatan sulfate exhibit inhibitory effects, chondroitin 6-sulfate shows a stimulating effect. In addition, the chondroitin 6-sulfate is also able to reduce the chondroitin 4-sulfate and dermatan sulfate specific inhibition.

Animals↗
PubMed1996

Reversible denaturation of cyclosporin synthetase by urea.

The reversible denaturation of the multifunctional polypeptide, cyclosporin synthetase, by urea was analyzed. It is possible to discriminate between at least two stages of enzyme denaturation. While at low urea concentration (up to 0.8M) cyclosporin A formation is inhibited, synthesis of the diketopiperazine cyclo-(D-alanyl-N-methylleucyl), a molecule representing a partial sequence of cyclosporin A is still detectable. At higher concentrations of urea the enzyme preparation is totally inactive. This inactivation is a consequence of conformational change(s) of cyclosporin synthetase as shown by fluorescence emission spectra of native and denatured enzyme. These data imply a consecutive folding/defolding mechanism for the different domains forming the multifuntional polypeptide.

Cyclosporine↗
PubMed1996

A simple and versatile PSA system for heavy metal determinations.

An easy to build potentiometric stripping analysis system for heavy metal determinations (Zn, Cd, Pb, Cu) is described which reaches good sensitivity and precision. Main components are an IBM compatible computer, an ADDA-conversion card and two selfmade electrodes, so it can be realized for one tenth of the price of complete commercial systems. A graphite pencil lead covered with a Hg-film is used as working electrode and a Ag/AgCl electrode as a combined reference/counter electrode. Reproducibility and calibration measurements are reported, heavy metal determinations on soil samples are compared with AAS results.

Journal Article↗
PubMed1996

Flow cytometric detection of platelet-reactive antibodies and application in platelet crossmatching.

BACKGROUND: Alloimmunization against HLA or platelet antigens can cause refractoriness to platelet transfusions in multiply transfused patients. Crossmatching of platelet concentrates is effective in overcoming this problem. STUDY DESIGN AND METHODS: A flow cytometric assay was used for simultaneous detection of lymphocyte-reactive and platelet-reactive antibodies in a single sample using fluorescein isothiocyanate-labeled anti-IgG. This assay was compared with the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay in selected sera containing HLA and platelet antibodies. In a further study, this assay was compared with lymphocytotoxicity test results from thrombocytopenic patients, for whom platelet concentrates were ordered. The results of both assays were then correlated with the 1-hour corrected count increment, with a corrected count increment greater then 7500 considered as an adequate transfusion response. RESULTS: The results of the MAIPA and flow cytometric assay in detecting platelet-reactive antibodies correlated well (p<0.0001, r = 0.84). The sensitivity and specificity of the flow cytometric assay in detecting platelet-reactive antibodies were 94.7 and 96.3 percent, when the MAIPA assay was taken as a reference. In unselected sera from patients, the sensitivity and specificity of the flow cytometric assays were, respectively, 72.7 and 91.7 percent in detecting lymphocyte-reactive antibodies and 70.6 and 77.7 percent in detecting platelet-reactive antibodies, when the lymphocytotoxicity test was used as a reference. With regard to an adequate transfusion response, the sensitivities and efficiencies were 20.0 and 82.1 percent, 33.3 and 84.3 percent, and 70.0 and 88.6 percent for the lymphocytotoxicity test and the lymphocyte-reactive and platelet-reactive flow cytometric assays, respectively. CONCLUSION: Flow cytometric crossmatching appears to be an effective method of detecting platelet-reactive antibodies that may affect the success of platelet transfusions. This procedure is well-suited for routine conditions and can be performed within 2 hours.

Antibodies, Monoclonal↗
PubMed1996

Characterization of differing effects caused by homeopathically prepared and conventional dilutions using cytochrome P450 2E1 and other enzymes as detection systems.

Determination of cytochrome P450 2E1 activity was carried out via hydroxylation of the synthetic substrate p-nitrophenol to p-nitrocatechol. Crude microsomal preparation isolated from rat liver served as source for cytochrome P450 2E1. Under assay conditions guaranteeing a linear course of the reaction the cytochrome P450 2E1 was stimulated in the presence of a 10(-6) dilution of As2O3 corresponding to 0.915 microM final concentration compared with control. All other concentrations of As2O3 used inhibited the enzyme activity more or less drastically. Furthermore, we used this enzyme system to study the influence of arsenicum album (As2O3) and potassium cyanatum (KCN) in homeopathically prepared (i.e., by consecutive 1:10 steps) and conventional dilutions. We found significant differences between the effects caused by homeopathic potencies (D) and equally concentrated dilutions on catalytic activity of cytochrome P450 2E1. Such differing effects were observed in the case of arsenicum album (As2O3) between D4/10(-4) and D6/10(-6) and in the case of potassium cyanatum (KCN) between D6/10(-6) and D12/10(-12). When we used glutathione-S-transferases and uricase we also found different effects mediated by potencies and conventional dilutions. The results obtained suggest that these three enzyme systems are appropriate detection systems to hunt out differing effects of differently prepared dilutions of specific test substances.

Animals↗
PubMed1996

[Immunologic effects of blood donation].

The effects of blood transfusion and blood donation on the immune system are still unclear. In a prospective study we investigated the effect of blood and blood component donation on several immunologic parameters. Lymphocyte subsets and cytokine levels were determined in 25 repeat whole-blood donors (RD), 25 plateletpheresis donors (PD), and 20 autologous blood donors (AD). First-time donors (FTD, n = 20) served as controls. Lymphocyte subsets and cytokines were determined using standard methods. Leukocytes, T-suppressor cells and natural killer (NK) cells were decreased in RD and PD when compared to FTD. Additionally, NK cells decreased with repeat donations in AD. No significant differences of cytokines in the different groups or during repeat autologous donations were observed.

Adult↗
PubMed1995

Prestorage leukocyte depletion with in-line filtration of whole blood in comparison with blood component leukocyte depletion.

In-line filtration of blood components appears to be an effective method to reduce white-cell-induced adverse reactions. We have investigated whether whole blood filtration (WBF), prior to component preparation, is comparable with filtration of already prepared blood components (CF), i.e. the red cell concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood components served as a control. No significant differences for most parameters investigated were found between leukodepleted RCCs and plasma units prepared by CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell contaminations < 1 x 10(5) per unit. Platelets were reduced in all filtered components: 95% in plasma and 99% in RCCs. Fresh-frozen plasma (FFP) prepared by CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and thrombin-antithrombin-III complexes, whereas platelet factor 4 (PF-4) was slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from filtered whole blood (n = 20) had a significantly greater volume (RCC: 288 +/- 19 ml; plasma: 274 +/- 20 ml) than conventionally prepared (n = 20) and filtered products (RCC: 257 +/- 19 ml, plasma: 259 +/- 19 ml). For early filtration of blood components, WBF prior to component preparation seems to offer an interesting technique for obtaining a leukocyte-depleted RCC and FFP.

Blood Cell Count↗
PubMed1994

Mechanism of cyclosporin A biosynthesis. Evidence for synthesis via a single linear undecapeptide precursor.

Cyclosporin A is synthesized by cyclosporin synthetase, a multienzyme polypeptide. This enzyme catalyzes at least 40 reaction steps in an assembly belt-like mechanism. It activates all constituent amino acids of cyclosporin A to thioesters via amino acyladenylates and carries out specific N-methylation reactions. During elongation, the activated amino acids are linked by peptide bonds leading to enzyme-bound nascent peptide chains. Some of the linear peptides of the growing cyclosporin A chain were isolated and their N-terminal amino acid was determined. D-Alanine at position 8 of the cyclosporin A molecule was found to be a starting amino acid in the biosynthetic process of cyclosporin A formation. Four intermediate peptides of the growing peptide chain of cyclosporin A could be isolated and identified. All of them represent partial sequences of cyclosporin A starting with D-alanine. That these intermediate peptides were bound by thioester linkage to cyclosporin synthetase could be demonstrated by liberation of the peptides with performic acid. The peptides strongly suggest the stepwise synthesis of a single linear peptide precursor of cyclosporin A.

2,2'-Dipyridyl↗
PubMed1994

Temperature dependent influence of As2O3, HgHPO4 and KCl on lysosomal acid phosphatase isolated from rat liver.

Studies were carried out to investigate acid phosphatase activity in the presence of As2O3, HgHPO4 and KCl at 25 degrees C and 37 degrees C. In all cases examined enzyme activities measured at 25 degrees differ from those detected at 37 degrees C. When activity was measured in the presence of As2O3 at 25 degrees C a stimulation was found while at 37 degrees C activities remained within the control range. Similar results were obtained, when As2O3 was replaced by HgHPO4. In contrast to that, added amounts of KCl cause an increase of activity at both incubation temperatures, but the increment being greater at 37 degrees C. Furthermore in most cases correlation between increasing amounts of substances added and enzyme activity measured was non-linear.

Acid Phosphatase↗