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Biomedical subjects

J Wilhelm

Publications and source records attributed to J Wilhelm.

At least 19 recordsLinked to original sources
PubMed2006

Biological markers to predict previous alcohol withdrawal seizures: a risk assessment.

Recent studies have shown that both, elevated homocysteine and prolactin plasma levels are associated with a higher risk of alcohol withdrawal seizures. The aim of this study was to evaluate the predictive qualities of a combined assessment of homocysteine and prolactin for previous alcohol withdrawal seizures. Therefore, 117 male patients suffering from alcohol dependency were included into the study. Homocysteine was measured directly at admission, prolactin the morning following admission for detoxification treatment. Pearson's chi(2)-test showed significant results for the combined assessment of both parameters (chi(2) = 14.71, p = 0.001). Multivariate logistic regression also revealed significant predictive qualities (p = 0.001, OR = 9.23, 95%CI = 2.36-36.05). A combination of both, homocysteine and prolactin, may help to assess the individual risk of alcohol withdrawal seizures in clinical practice.

Adult↗
PubMed2006

The effect of plant cytokinin hormones on the production of ethylene, nitric oxide, and protein nitrotyrosine in ageing tobacco leaves.

Transgenic plants with genetically increased or decreased levels of cytokinins were used to investigate the effect of cytokinin level on the production of ethylene, a plant hormone with suggested role in senescence, and the production of nitric oxide, potentially important signalling and regulatory molecule. The production of these gases was followed during the course of leaf development and senescence. The production of ethylene and nitric oxide is under genetic control of genes other than those involved in regulation of senescence. The difference in basic ethylene and NO levels in different tobacco cultivars was higher than their changes in senescence. The results of this study did not indicate a direct link between ethylene production and cytokinin levels. However, there was a decreased production of NO in senescent leaves. Low cytokinins level was associated with increased NO production during leaf development. Protein nitrotyrosine proved to be a better indicator of the reactive nitrogen species than measuring of the NO production. Higher nitrotyrosine concentrations were found in insoluble proteins than in the soluble ones, pointing to membrane proteins as the primary targets of the reactive nitrogen species. In plants with elevated cytokinin levels the content of nitrated proteins decreased both in soluble and insoluble fractions. This finding indicates an antioxidative function of cytokinins against reactive nitrogen species.

Cytokinins↗
PubMed2005

Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism.

Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p=0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald chi2=4.071, OR=1.043, 95% CI 1.001-1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC=0.68, 95% CI=0.57-0.79, p=0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal.

Adult↗
PubMed2005

Erythrocyte membranes inhibit respiratory burst and protein nitration during phagocytosis by macrophages.

Phagocytosis is associated with respiratory burst producing reactive oxygen and nitrogen species. Several studies imply that erythrocytes can inhibit the respiratory burst during erythrophagocytosis. In this work we studied the mechanisms of this effect using control and in vitro peroxidized erythrocyte membranes. We demonstrated that autofluorescence of peroxidation products can be used for visualization of phagocytozed membranes by fluorescence microscopy. We also found that respiratory burst induced by a phorbol ester was inhibited by control membranes (5 mg/ml) to 63 % (P < 0.001), and to 40 % by peroxidized membranes (P < 0.001). We proved that this effect is not caused by the direct interaction of membranes with free radicals or by the interference with luminol chemiluminescence used for the detection of respiratory burst. There are indications of the inhibitory effects of iron ions and free radical products. Macrophages containing ingested erythrocyte membranes do not contain protein-bound nitrotyrosine. These observations imply a specific mechanism of erythrocyte phagocytosis.

Animals↗
PubMed2005

Homocysteine plasma levels are elevated in females with anorexia nervosa.

In the present pilot study significantly (T = 2.46, P = 0.018) higher levels of homocysteine were found in female anorectic patients (14.07, SD 7.3 micromol/l; n = 18) when compared with bulimic patients (10.25, SD 2.82; n = 27) or healthy controls (8.10, SD 1.79; n = 25). Since homocysteine can induce neuronal cell death leading to brain atrophy in different diseases and since it has been linked to depressive disorders these findings may have important implications for understanding common symptoms in patients suffering from anorexia.

Adolescent↗
PubMed2005

Cognitive impairment and its association with homocysteine plasma levels in females with eating disorders - findings from the HEaD-study.

Higher plasma homocysteine levels have been found in females with anorexia nervosa. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and healthy elderly people. Aim of this prospective study was to investigate a possible association between homocysteine serum levels and Clinically well known cognitive deficits in females with eating disorders. We found that moderately elevated plasma homocysteine levels were associated with normal short- and long-term verbal memory while normal plasma homocysteine levels were associated with poorer memory performance in 14 females with anorexia nervosa and 12 females with bulimia nervosa (logistic forward regression Wald chi(2)=8.566, OR=24.75, CI 2.89 - 212.23, P=0.003). These results indicate that under the special circumstances of eating disorders elevated homocysteine levels improve memory signaling possibly by facilitating long-term potentiation.

Adolescent↗
PubMed2004

Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine.

An important lesion in Alzheimer's disease (AD) patient brains is the neurofibrillary tangle (NFT). Hyperphosphorylated tau is its major component. In a former paper we described some NFT in the canine brain. During aging, moreover, advanced glycation end products (AGE) might accumulate. Glycated tau induces lipid peroxidation in vivo and tau and AGE antigens have been mentioned to co-localize in NFT. This indicates that AGE may play an important role in Alzheimer disease (AD) by oxidation of tau. The aim of the present study was to investigate amyloid, neurofibrillary tangles, Abeta precursor protein, Abeta, tau, ubiquitin, advanced glycation end products, 4-hyroxynonenal protein and lipofuscin in a series of dogs of varying ages. The results showed a significant positive correlation between age and amyloid quantity (Congo red staining), HNE staining and lipofuscin (LF), and between amyloid quantity and HNE staining and LF. Staining for AbetaPP seemed to have a tendency to increase with age, whereas staining for tau, ubiquitin and AGE each only gave limited positive results in a proportion of the older dogs. Preliminary studies including loss of cognitive capabilities in the older dogs and chemical measurement of lipofuscin-like pigment (LFP) accumulation in brain extracts revealed an increase with old age and dementia. The Congo red, HNE and LF results suggest that deposition of amyloid with aging might be associated with formation of end products of lipid peroxidation. The finding of the limited positive signals for tau, ubiquitin and AGE in some old cases might indicate that the spontaneous brain pathology of the aged dog reveals similarities to early stages observed in AD in humans especially those with Down syndrome.

Aging↗
PubMed2004

Assessment of exhaled gases in ventilated preterm infants.

Hydrogen peroxide (H2O2) production in exhaled air was measured in ventilated preterm newborns at 5, 24 and 48 hours after delivery, using originally designed method of exhaled breath condensate (EBC) collection. H2O2 production in expired gas was 812+/-34 pmol/20 min during the first measurement and then declined to 389+/-21 at 24 hours and 259+/-26 pmol/20 min at 48 hours.

Breath Tests↗
PubMed2003

Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism.

Chronic alcohol consumption can induce brain atrophy, whereby the exact mechanism of brain damage in alcoholics remains unknown. There is evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury in vitro and in vivo. The present volumetric magnetic resonance imaging study included 52 chronic alcoholics and 30 non-drinking healthy controls. Patients were active drinkers and had an established diagnosis of alcohol dependence. We investigated the influence of different variables on the hippocampal volume of patients suffering from chronic alcoholism. We observed that pathological raised levels of plasma homocysteine showed the most significant correlation to hippocampal volume reduction (P<0.001, multiple regression analysis). Raised plasma levels of homocysteine are associated with hippocampal (brain) atrophy in alcoholism.

Adult↗
PubMed2003

Apolipoprotein E epsilon 4 is associated with hippocampal volume reduction in females with alcoholism.

There is evidence that a higher incidence of diverse neurodegenerative diseases is associated with the apolipoprotein E epsilon4 allele (ApoE4). Most recently it has been found that the ApoE4 allele is specifically related to an accelerated hippocampal atrophy in patients with Alzheimer's disease. Therefore, the aim of the present study was to investigate the association between ApoE4 genotypes and brain hippocampal volume reduction in alcoholics by using volumetric high-resolution MR imaging. In the present study, female alcoholics with the ApoE4 genotype were found to have significantly smaller hippocampal volumes than those not carrying an epsilon4 allele (ANOVA, p < 0.05), whereas no differences in hippocampal volume were seen in male alcoholics. Since hippocampal volume reduction is lately discussed to be proportional to brain atrophy, we propose that the alcohol-related brain atrophy in patients suffering from chronic alcoholism, is more pronounced in female carriers of the apoE epsilon4 allele. These findings indicate a genetic disposition for alcohol related brain atrophy in female carrying the ApoE4 genotype, which may also explain why female alcoholics are more susceptible to alcohol-induced brain damage.

Adult↗
PubMed2003

The role of free radicals in canine counterpart of senile dementia of the Alzheimer type.

The pathogenesis of Alzheimer's disease is still unknown. In recent time oxidative stress has been discussed as an important contributor. In the present study we investigated the role of free radicals in the spontaneous canine model of Alzheimer's disease. We analysed end-products of lipid peroxidation: lipofuscin-like pigments (LFP), protein carbonyls, and vitamin E to obtain data on oxidative damage in brain of demented dogs. When the generation of free radicals is intensive the toxic products of lipid peroxidation can diffuse from the site of the primary formation and merge with erythrocytes. Therefore we also determined the level of lipid peroxidation in red blood cells. In brain of demented animals the level of LFP increased (to 247%, P<0.05) as well as of protein carbonyls (to 438%, P<0.01) while the vitamin E concentration was lowered (to 34%, P<0.01) when compared to age-matched non-demented controls. The end-products of lipid peroxidation have been found increased also in erythrocytes of demented dogs (250%, P<0.05). These results indicate intensive production of free radicals in brain of animals with dementia which induces damage to erythrocytes. Detection of the specific products of free radical damage in blood samples could be used for diagnostic purposes.

Alzheimer Disease↗
PubMed2003

Hypoxia and reoxygenation increase H2O2 production in rats.

To test the effect of transition from sustained hypoxia to normoxia on production of reactive oxygen species (ROS) in lungs, the authors measured hydrogen peroxide (H(2)O(2)) output in the expired air of rats breathing hypoxic, normoxic, and hyperoxic gas mixtures at the end of exposure to 72 hours of hypoxia. Twenty-one male Wistar rats (200 to 280 g) were randomly assigned to 1 of 3 groups. First two groups (experimental) were kept for 3 days in normobaric hypoxic chamber (F(1)O(2) 0.1), rats of the third group (controls) breathed air. The rats were then anesthetized, intubated, placed in the plethysmograph, and their ventilation measured. Two periods of exhaled breath condensate (EBC) collection, each lasting 1 hour, were then performed to assay H(2)O(2) output. The controls breathed during both samplings air, the first experimental group breathed during first sampling period hypoxic mixture (F(1)O(2) 0.1; SH-H measurement) and then, during second period, air (SH-H-A measurement), the second experimental group breathed first air (SH-A measurement) and then hyperoxic mixture (F(1)O(2) 1.0; SH-A-O(2) measurement). Concentration of H(2)O(2) in the EBC was assayed by chemiluminescence. H(2)O(2) production in the control group was low and similar in both measurements (20+/-10 and 13+/-5 pmol/h, mean+/-SEM). Exposure to 72 hours of hypoxia increased the H(2)O(2) production to 105+/-18 pmol/h (SH-H). Transition from hypoxia to normoxia resulted in an increase in the H(2)O(2) production (SH-A 421+/-24 pmol/h, and SH-H-A 366+/-19 pmol/h). Following transition from air breathing to hyperoxia did not affect the H(2)O(2) production (SH-A-O(2) 373+/-25 pmol/h). The results showed that sustained hypoxia and transition from sustained hypoxia to normoxia increased H(2)O(2) formation in the lungs.

Animals↗
PubMed2003

[Markers of lung disease in expired air].

Many chronic inflammatory pulmonary diseases are associated with inflammation and oxidative stress. A complex interplay between the specific cause of the diseases, the type and intensity of inflammation and oxidative stress, results in the clinical picture and reveals the probability of progression of the specific disease. The presence of inflammation and oxidative stress has been established in interstitial lung diseases, cystic fibrosis, bronchiectasis, adult respiratory distress syndrome, chronic obstructive lung diseases and asthma. Noninvasively obtained markers of inflammation and oxidative stress from the breath may assist in diagnosis of pulmonary diseases, assessment of diseases severity and response to treatment. Exhaled markers include NO, CO, H2O2, ethane, pentane, and isoprostanes.

Biomarkers↗
PubMed2003

Hydrogen peroxide production by alveolar macrophages is increased and its concentration is elevated in the breath of rats exposed to hypoxia: relationship to lung lipid peroxidation.

Hypoxic exposure triggers a generation of reactive oxygen species that initiate free radical damage to the lung. Hydrogen peroxide is the product of alveolar macrophages detectable in the expired breath. We evaluated the significance of breath H(2)O(2) concentration for the assessment of lung damage after hypoxic exposure and during posthypoxic period. Adult male rats were exposed to normobaric hypoxia (10 % O(2)) for 3 hours or 5 days. Immediately after the hypoxic exposure and then after 7 days or 14 days of air breathing, H(2)O(2) was determined in the breath condensate and in isolated lung macrophages. Lipid peroxidation was measured in lung homogenates. Three-hour hypoxia did not cause immediate increase in the breath H(2)O(2); 5-day hypoxia increased breath H(2)O(2) level to 458 %. After 7 days of subsequent air breathing H2O2 was elevated in both groups exposed to hypoxia. Increased production of H(2)O(2) by macrophages was observed after 5 days of hypoxia and during the 7 days of subsequent air breathing. Lipid peroxidation increased in the periods of enhanced H(2)O(2) generation by macrophages. As the major increase (1040 %) in the breath H(2)O(2) concentration found 7 days after 3 hours of hypoxia was not accompanied by lipid peroxidation, it can be concluded that the breath H(2)O(2) is not a reliable indicator of lung oxidative damage.

Aldehydes↗
PubMed2002

The role of carbon dioxide in free radical reactions of the organism.

Carbon dioxide interacts both with reactive nitrogen species and reactive oxygen species. In the presence of superoxide, NO reacts to form peroxynitrite that reacts with CO2 to give nitrosoperoxycarbonate. This compound rearranges to nitrocarbonate which is prone to further reactions. In an aqueous environment, the most probable reaction is hydrolysis producing carbonate and nitrate. Thus the net effect of CO2 is scavenging of peroxynitrite and prevention of nitration and oxidative damage. However, in a nonpolar environment of membranes, nitrocarbonate undergoes other reactions leading to nitration of proteins and oxidative damage. When NO reacts with oxygen in the absence of superoxide, a nitrating species N2O3 is formed. CO2 interacts with N2O3 to produce a nitrosyl compound that, under physiological pH, is hydrolyzed to nitrous and carbonic acid. In this way, CO2 also prevents nitration reactions. CO2 protects superoxide dismutase against oxidative damage induced by hydrogen peroxide. However, in this reaction carbonate radicals are formed which can propagate the oxidative damage. It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions.

Animals↗
PubMed2001

Solution structure of human IL-13 and implication for receptor binding.

Interleukin-13 has been implicated as a key factor in asthma, allergy, atopy and inflammatory response, establishing the protein as a valuable therapeutic target. The high-resolution solution structure of human IL-13 has been determined by multidimensional NMR. The resulting structure is consistent with previous short-chain left-handed four-helix bundles, where a significant similarity in the folding topology between IL-13 and IL-4 was observed. IL-13 shares a significant overlap in biological function with IL-4, a result of the common alpha chain component (IL-4Ralpha) in their respective receptors. Based on the available structural and mutational data, an IL-13/IL-4Ralpha model and a sequential mechanism for forming the signaling heterodimer is proposed for IL-13.

Amino Acid Sequence↗
PubMed2001

Influence of fluorophor dye labels on the migration behavior of polymerase chain reaction--amplified short tandem repeats during denaturing capillary electrophoresis.

The determination of the length of polymerase chain reaction (PCR)-amplified short tandem repeats (STRs) by denaturing capillary electrophoresis (CE) is a standard procedure for purposes of genotyping. We show that dye-specific mobility anomalies exist for 5'-fluorophor-labelled single-stranded DNA (ssDNA) fragments in CE using the performance-optimized polymer 4 (POP4) buffer sieving matrix, containing the entangled poly(N,N-dimethylacrylamide) polymer, urea, and 2-pyrrolidinone. The dye-specific retardation effects relative to coseparated GeneScan-500 [TAMRA] standard fragments can lead to wrong genotyping, even for allele-specific fragments of pentanucleotide STRs, when comparing the relative calculated sizes of identical fragments, labelled with rhodamine (ROX, TAMRA) or fluorescein dyes (FAM, 6-FAM, HEX, JOE, NED, TET): The size of fluorescein dye-labelled fragments of appr. 100 b in length appears to be smaller by up to 6.5 b. This effect becomes more dramatic with decreasing size: a 6-FAM-labelled 24-mer oligonucleotide appeared to be smaller by 11 b. In contrast, in classical urea/polyacrylamide slab-gel electrophoresis only a small dye-specific retardation of identical fragments is observed. The dye-specific effects are superimposed by weaker size and sequence-dependent anomalies of fragment mobility. Therefore, in denaturing CE the coseparation of a defined allele ladder labelled with the same dye as the unknown sample fragments remains the method of choice for accurate genotyping.

DNA, Single-Stranded↗