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W Henke

Publications and source records attributed to W Henke.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparison between equimolar- and skewed-response assays of prostate specific antigen: is there an influence on the clinical significance when measuring total serum prostate specific antigen?

Using the Tandem-E, Axsym and LIA-mat assays, prostate specific antigen (PSA) was measured in pure PSA solutions of known concentrations of free and complexed PSA and in serum of patients with prostate cancer (n = 31), benign prostate hyperplasia (n = 32) and in healthy controls (n = 27). Measurements of pure PSA solutions showed that the AxSym assay exemplified typical properties of the skewed-response assay reacting more to free PSA than to the complexed PSA forms whereas the other two assays showed an equimolar-response. When PSA was measured in the serum of the tree groups, the AxSym test and Tandem-E gave similar PSA values whereas the LIA-mat test yielded significantly lower values. These results were not related to the amount of free PSA in the samples and proved that discordant PSA values between PSA assays were not mainly caused by the use of skewed- or equimolar assays. Despite these differences, receiver-operation characteristic analysis confirmed that the clinical validity of all three PSA tests did not differ.

Aged↗
PubMed1996

The effect of the lipid peroxidation product 4-hydroxynonenal and of its metabolite 4-hydroxynonenoic acid on respiration of rat kidney cortex mitochondria.

In rat kidney cortex mitochondria, 4-hydroxynonenal inhibits state 3 respiration as well as uncoupled respiration at micromolar concentrations. The inhibition is more distinct for NAD-linked than for FAD-linked respiration. 4-Hydroxynonenal increases the state 4 respiration. It is assumed that 4-hydroxynonenal behaves like a decoupling agent. 4-Hydroxynonenal augments the inhibitory effect of 2,4-dinitrophenol observed at superoptimal concentrations. 4-Hydroxynonenal is metabolised by renal mitochondria, and 4-hydroxynonenoic acid is one of the metabolites generated. This metabolite is without effect on respiration at concentrations up to 50 microM. Therefore, the effect of 4-hydroxynonenal on respiration is not mediated by this fatty acid derivative formed during respiratory measurements.

Aldehydes↗
PubMed1996

Analytical performance and clinical validity of two free prostate-specific antigen assays compared.

We compared two recently introduced commercial assays (CanAg and Immulite) for measuring free prostate-specific antigen (f-PSA), total PSA (t-PSA), and the ratio of t-PSA/f-PSA (f-PSA%) in control materials and sera of 54 healthy men, 50 patients with benign prostatic hyperplasia (BPH), and 45 patients with prostate cancer (PCa). The lower detection limits for f-PSA were 0.038 microgram/L and 0.004 microgram/L for the CanAg and Immulite assays, respectively. The within-run and between-day precisions of the Immulite assay were < 5%; the CanAg assay showed a poorer precision. Whereas f-PSA values differed between controls and patients but not between BPH and PCa patients, the f-PSA% values were lower in PCa patients than in BPH patients and controls. The receiver-operating characteristic (ROC) curve showed an improved diagnostic power of f-PSA% compared with t-PSA to discriminate between BPH and PCa. Discrimination limits of 16% (CanAg assay), and 15% (Immulite assay) are recommended for f-PSA%.

Autoanalysis↗
PubMed1996

Strip test for the quick detection of increased concentrations of prostate-specific antigen in blood.

We tested the performance of the new immunochemical membrane test BioSign PSA for detecting serum concentrations of prostate-specific antigen > 4 micrograms/l. Measurements were simultaneously performed on 161 serum samples, using the strip test and three quantitative assays of prostate specific antigen (Tandem-E, IMx, LIA-mat). Based on the upper reference limit of 4 micrograms/l, 11-37% of the results obtained with the BioSign test were false-negative and 4-15% were false-positive, compared with the data of the three quantitative assays. It is concluded that the BioSign test in its present form does not satisfactorily differentiate between prostate-specific antigen concentrations above and below 4 micrograms/l, but an improved version of the test would be useful.

Adult↗
PubMed1995

Effects of preservation solutions on cortical and medullary mitochondria of rat kidney.

The mitochondria isolated from cortex and medulla of rat kidneys were examined after storage in either Euro-Collins solution, in Bretschneider's histidine-tryptophan-ketoglutarat solution or in Belzer's University of Wisconsin solution at 25 degrees C or at 4 degrees C for a maximum of 4 to 24 hrs. Independently to the preservation of the solution used, the storage of the kidneys led to a decrease in state 3 respiration and uncoupled respiration as well as to an increase in the rate of state 4 respiration. The decrease in state 3 respiration ran parallelly to a decrease in adenine nucleotides. For the homogeneous protection of the mitochondria as well from the cortex as from the medulla, the Bretschneider's solution had the best preservative effect at a storage temperature of 25 degrees C as shown by the measured mitochondrial parameters. At 4 degrees C storage temperature, the differences in action with the various examined solutions were markedly smaller. However, compared to the other two solutions, the Euro-Collins solution showed a more favourable protective effect on cortical and medullary mitochondria.

Adenine Nucleotides↗
PubMed1994

Identification of metabolic pathways of the lipid peroxidation product 4-hydroxynonenal by mitochondria isolated from rat kidney cortex.

The cytosolic lipid peroxidation product 4-hydroxynonenal (HNE) is rapidly metabolized in mitochondria isolated from rat kidney cortex. About 80% of HNE was degraded within 3 min of incubation. Main products of HNE which were identified in mitochondria were the hydroxynonenoic acid, the 1,4-dihydroxynonene and the glutathione-HNE-conjugate. Furthermore, formation of metabolites of the tricarboxylic acid cycle from HNE is suggested. The quantitative share of HNE binding to proteins was high with about 8% of total HNE consumption after 3 min of incubation. Therefore, rapid degradation of HNE by mitochondria might be involved in an intracellular antioxidative defense system.

Aldehydes↗
PubMed1993

Comparison of the effects of the immunosuppressive agents FK 506 and cyclosporin A on rat kidney mitochondria.

Interactions of FK 506 with renal cortical mitochondria have been investigated by measuring respiration, ATP net uptake and Ca2+/Pi-induced swelling. Both FK 506 and cyclosporin A (CsA) inhibit the succinate-supported state 3 and uncoupled respiration and are without effect on the glutamate/malate-supported state 3 and uncoupled respiration. FK 506, like CsA, inhibits net uptake of ATP, but, in contrast to CsA, is without effect on Ca2+/Pi-induced swelling.

Adenosine Triphosphate↗
PubMed1993

Net adenine nucleotide transport in rat kidney mitochondria.

This study investigated the hypothesis that changes in the adenine nucleotide (ATP + ADP + AMP) content of kidney mitochondria can occur by a transport mechanism that catalyzes net transfer of adenine nucleotides across the inner mitochondrial membrane. The adenine nucleotide content of isolated kidney mitochondria was 8.23 +/- 0.85 nmol/mg mitochondrial protein. This amount increased or decreased as a function of the external [ATP-Mg] when mitochondria were incubated in phosphate-containing medium. The increases and decreases were inhibited to different extents by 100 microM EGTA (ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid) or 5 microM carboxyatractyloside (CAT), suggesting two transport mechanisms. The unidirectional components (influx and efflux) of net flux were examined separately for the CAT-insensitive (EGTA-sensitive) and CAT-sensitive (EGTA-insensitive) mechanisms. CAT-insensitive adenine nucleotide influx and efflux were stimulated by [Ca2+]free up to 2 microM; for ATP influx, Km was 1.7 mM, Vmax was 3.5 nmol/min/mg protein, and Mg2+ was required. Efflux varied as a function of both the external and matrix [ATP] and was completely inhibited by mersalyl. ATP was a better substrate than ADP, and ADP transport did not require Mg2+. The CAT-sensitive mechanism was characterized by studying phosphate-induced adenine nucleotide efflux. Efflux varied with external [Pi] and with matrix [ATP] and was not inhibited by cyclosporin. The amount of CAT required for maximal inhibition was 800 pmol/mg protein. In contrast to CAT-insensitive efflux, this pathway was only partially inhibited by mersalyl and showed no preference for ATP vs ADP. In conclusion, two distinct mechanisms for net adenine nucleotide transport were demonstrated. Both exchange adenine nucleotides (ATP-Mg or ADP) for Pi. One mechanism is identical to the CAT-insensitive ATP-Mg/Pi carrier known in liver mitochondria; the other is a CAT-sensitive mechanism that is not present in liver and may represent a novel function of the ADP/ATP translocase or another CAT-sensitive carrier.

Adenine Nucleotides↗
PubMed1993

Effect of storage temperature on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in rat liver and kidney homogenates.

The behavior of the catalytic activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase was tested in rat liver and kidney homogenates stored at 4, -20 and -70 degrees C and in corresponding tissue samples stored at -70 degrees C. The stabilities of enzymes were different for various enzymes and were dependent on the organ (liver, kidney) and the storage temperature. The storage temperature of -70 degrees C guaranteed the best stability and the five enzymes investigated were sufficiently stable in preserved tissue samples or in homogenates prepared with conventional mannit/sucrose homogenization solution. Under such conditions, these enzymes were stable over at least 4 or 1 weeks, respectively.

Animals↗
PubMed1992

Cyclosporine A inhibits ATP net uptake of rat kidney mitochondria.

The adenine nucleotide content of mitochondria varies at several physiological and pathological situations. Both net transport and intramitochondrial catabolism of adenine nucleotides has been suggested to be responsible for these changes. Here, the influence of cyclosporine A on the ATP net uptake of isolated rat kidney mitochondria was examined. The ATP net uptake of mitochondria depleted of matrix adenine nucleotides by pyrophosphate treatment was inhibited by cyclosporine A showing a I50 value of about 4 nmol/mg mitochondrial protein. Because intramitochondrial adenine nucleotide content is important for several mitochondrial functions such as oxidative phosphorylation, Ca2+ homoeostasis and mitochondrial biogenesis, it is concluded that the inhibition of adenine nucleotide net transport and a decrease of adenine nucleotide content may be involved in the immunosuppressive and nephrotoxic effects of cyclosporine A.

Adenosine Diphosphate↗
PubMed1992

The contribution of adenine nucleotide loss to ischemia-induced impairment of rat kidney cortex mitochondria.

Adenine nucleotides and respiration were assayed with rat kidney mitochondria depleted of adenine nucleotides by pyrophosphate treatment and by normothermic ischemia, respectively, with the aim of identifying net uptake of ATP as well as elucidating the contribution of adenine nucleotide loss to the ischemic impairment of oxidative phosphorylation. Treatment of rat kidney mitochondria with pyrophosphate caused a loss of adenine nucleotides as well as a decrease of state 3 respiration. After incubation of pyrophosphate-treated mitochondria with ATP, Mg2+ and phosphate, the content of adenine nucleotides increased. We propose that kidney mitochondria possess a mechanism for net uptake of ATP. Restoration of a normal content of matrix adenine nucleotides was related to full recovery of the rate of state 3 respiration. A hyperbolic relationship between the matrix content of adenine nucleotides and the rate of state 3 respiration was observed. Mitochondria isolated from kidneys exposed to normothermic ischemia were characterized by a decrease in the content of adenine nucleotides as well as in state 3 respiration. Incubation of ischemic mitochondria with ATP, Mg2+ and phosphate restored the content of adenine nucleotides to values measured in freshly-isolated mitochondria. State 3 respiration of ischemic mitochondria reloaded with ATP recovered only partially. The rate of state 3 respiration increased by ATP-reloading approached that of uncoupler-stimulated respiration measured with ischemic mitochondria. These findings suggest that the decrease of matrix adenine nucleotides contributes to the impairment of ischemic mitochondria as well as underlining the occurrence of additional molecular changes of respiratory chain limiting the oxidative phosphorylation.

Adenine Nucleotides↗
PubMed1992

Inhibition of skin allograft rejection and acute graft-versus-host disease by cis-urocanic acid.

Ultraviolet B radiation initiates a suppression of the delayed-type hypersensitivity response accompanied by a generation of antigen-specific suppressor cells and an alteration of antigen-presenting function. In previous studies we and other investigators could achieve a prolongation of graft survival by a treatment of the recipient with UVB light or 8-methoxy-psoralen plus UVA light (PUVA). One of the mediators of the systemic immunomodulatory effects of ultraviolet light or PUVA may be urocanic acid, which is isomerized in the skin by ultraviolet light from its cis- to the trans-isomer. In this work we present evidence that cis-urocanic acid, generated in vitro by a treatment with UVB light or PUVA, is able to prolong the survival of allogeneic MHC disparate skin grafts in mice. In contrast, the rejection of second set grafts was not suppressed. Unirradiated (trans-urocanic acid) had no effect on allograft rejection. In a murine model cis-, but not trans-urocanic acid, prevented or delayed an acute lethal graft-versus-host disease. These experiments demonstrate the potent systemic immunomodulatory effects of cis-urocanic acid in vivo.

Animals↗
PubMed1992

Adaptational increase of liver glutathione content during long-term application of cyclosporine A may attenuate toxic side effects.

The concentrations of reduced and oxidized glutathione and of adenine nucleotides were determined in liver, kidney and heart of rats during long-term (four weeks), high-dose therapy with cyclosporine A. In liver and kidney the concentration of oxidized glutathione increased following 4 weeks-therapy suggesting increased formation of free radicals and accelerated lipid peroxidation processes. These processes may be due to an increased activity of the cytochrome P-450 system. Compensatory levels of reduced glutathione were also increased. The adaptational increase of the tissue level of reduced glutathione, presumably the response to a chronic oxidative stress, was more distinct in the liver. The liver did not lose adenine nucleotides. In contrast the kidney, after 4 weeks of cyclosporine A therapy, lost 25% of the adenine nucleotides. These findings suggest that the liver is characterized by a greater potential for effective adaptation to oxidative stress conditions compared to the kidney. These adaptations may prevent distortions of energy and nucleotide metabolism in the liver which is in agreement with the minor ultrastructural changes we have observed.

Adaptation, Physiological↗
PubMed1992

Practical approach for determining glomerular filtration rate by single-injection inulin clearance.

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

Adult↗
PubMed1992

Cis-urocanic acid as a mediator of ultraviolet-light-induced immunosuppression.

Treatment of an organism with UVB light or PUVA (8-methoxypsoralen + UVA light) not only leads to alterations in the irradiated skin but also to systemic immunomodulation, due to the release of several chemical mediators of immunosuppression like prostaglandins, acute-phase proteins, IL-1 inhibitor, alpha-melanocyte-stimulating hormone, propiomelanocorticotropin or other cytokines. A recently described mediator is urocanic acid, which is transformed by UV light in the skin from the trans- to the cis-isomer and that exerts a systemic immunomodulatory effect. In our experiments, treatment with PUVA or with cis-urocanic acid prevents the rejection of rat heart allografts in 50% and 40% of cases, respectively. Control grafts are rejected in fewer than 10 days. PUVA treatment of donor leukocytes before transfusion into the prospective recipient inhibits only their sensitizing, not their graft-protecting, effect on subsequent skin grafts in mice. PUVA treatment also prevents acute lethal GVH disease in mice after irradiation with a sublethal dose of x-rays and transfusion of semiallogeneic spleen cells. Treatment of recipient mice with cis-urocanic acid has the same effect. The humoral immune response to sheep erythrocytes is not influenced by cis-urocanic acid. These results demonstrate that PUVA treatment or its chemical mediator, cis-urocanic acid, may be used in transplantation and hematology as naturally occurring immunosuppressive agents, especially for the control and manipulation of GVH leukemia reaction.

Animals↗