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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 73 records · Page 4Linked to original sources

The effects of conjugated linoleic acids or an alpha-glucosidase inhibitor on tissue lipid concentrations and fatty acid composition of broiler chicks fed a low-protein diet.

The effects of dietary conjugated linoleic acid (CLA) and an alpha-glucosidase inhibitor--Bay g 5421--on tissue lipid concentrations and fatty acid composition were investigated in male broiler chicks fed a low-protein diet. The trial comprised six isoenergetic broiler diets. One diet (high-protein diet) was used as a control diet and contained 230 g crude protein per kilogram. The other five diets were low-protein diets (180 g crude protein/kg) without additional supplement, or supplemented with 20 or 40 g/kg of a CLA-enriched oil, or supplemented with 50 or 100 mg of Bay g 5421/kg. Broilers fed the low-protein diets had higher concentrations of triglycerides and cholesterol in the liver than broilers fed the high-protein diet. Broilers fed low-protein diets supplemented with CLA had a higher cholesterol concentration in plasma, lower hepatic triglyceride concentrations, higher relative concentrations of saturated fatty acids (SFA), and lower relative concentrations of monounsaturated fatty acids (MUFA) in lipids of liver, thigh muscle, and adipose than broilers fed low-protein diets without CLA supplement. Broilers fed the low-protein diets supplemented with Bay g 5421 had lower concentrations of triglycerides and cholesterol in the liver and lower concentrations of triglycerides in plasma than broilers fed the low-protein diet without supplementation. Moreover, broilers fed diets with Bay g 5421 had higher relative concentrations of polyunsaturated fatty acids and lower relative concentrations of MUFA in lipids of liver, muscle, and adipose tissue. The results show that supplementation of the low-protein diets with CLA and Bay g 5421 affected tissue lipid concentrations and fatty acid composition in broilers, which are of practical relevance with regards to meat quality.

Acarbose↗

Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy.

We have recently shown that Okihiro syndrome results from mutation in the putative zinc finger transcription factor gene SALL4 on chromosome 20q13.13-13.2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome. We analysed further families/patients with the clinical diagnosis of Holt-Oram syndrome and acro-renal-ocular syndrome for SALL4 mutations. We identified a novel SALL4 mutation in one family where the father was originally thought to have thalidomide embryopathy and had a daughter with a similar phenotype. We also found two novel mutations in two German families originally diagnosed as Holt-Oram syndrome and a further mutation in one out of two families carrying the diagnosis acro-renal-ocular syndrome. Our results show that some cases of "thalidomide embryopathy" might be the result of SALL4 mutations, resulting in an increased risk for similarly affected offspring. Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations.

Abnormalities, Multiple↗

Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in a patient with a brain abscess caused by small colony variants.

A 45 year old man was admitted to hospital with a right sided facial paralysis and three month history of seizures. Computed tomography showed a left temporal mass including both intracerebral and extracerebral structures. Ten years earlier the patient had undergone a neurosurgical intervention in the same anatomical region to treat a subarachnoid haemorrhage. In tissue samples and pus obtained during neurosurgery, Staphylococcus aureus was detected by a 16S rRNA-directed in situ hybridisation technique. Following long term cultivation, small colony variants (SCV) of methicillin resistant S aureus were identified. The patient was treated successfully with a combination of vancomycin and rifampin followed by prolonged treatment with teicoplanin, with no sign of infection on follow up nine months after discharge. This is the first report in which S aureus SCV have been identified as causative organisms in a patient with brain abscess and in which in situ hybridisation has been used to detect S aureus in a clinical specimen containing SCV. Antimicrobial agents such as rifampin which have intracellular activity should be included in treatment of infections caused by S aureus SCV.

Brain Abscess↗

Molecular characterization of the canine HMGB1.

Due to the close similarities of numerous canine diseases to their human counterparts, the dog could join the mouse as the species of choice to unravel the genetic background of complex diseases as e.g. cancer and metabolic diseases. Accordingly, the role of the dog as a model for therapeutic approaches is strongly increasing. However, prerequisite for such studies is the characterization of the corresponding canine genes. Recently, the human high mobility group protein B1 (HMGB1) has attracted considerable interest of oncologists because of what is called its "double life". Besides its function as an architectural transcription factor HMGB1 can also be secreted by certain cells and then acts as a ligand for the receptor for advanced glycation end products (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways, such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1 in inflammation and tumor metastasis. These results make HMGB1 a very interesting target for therapeutic studies done in model organisms like the dog. In this study we characterized the molecular structure of the canine HMGB1 gene on genomic and cDNA levels, its predicted protein, the gene locus and a basic expression pattern.

Amino Acid Sequence↗

A rare case of Salmonella osteomyelitis in the humerus as a differential diagnosis to a malignant bone tumor.

Salmonella osteomyelitis without predisposing factors is seldom seen and thus difficult to diagnose. We report on a 14-year-old healthy boy with Salmonella osteomyelitis which occurred 2 years after trauma. Radical operative debridement is recommended. Intravenous ciprofloxacin has proved to be effective because of good tissue penetration and sensitivity towards Salmonella.

Adolescent↗

The thioredoxin system of Plasmodium falciparum and other parasites.

Antioxidant defence plays a crucial role in rapidly growing and multiplying organisms, including parasites and tumor cells. Apart from reactive oxygen species (ROS) produced in endogenous reactions, parasites are usually exposed to high ROS concentrations imposed by the host immune system. The glutathione and thioredoxin systems represent the two major antioxidant defence lines in most eukaryotes and prokaryotes. Trypanosomatids, however, are characterized by their unique trypanothione system. These systems are NADPH-dependent and based on the catalytic activity of the flavoenzymes glutathione reductase, trypanothione reductase and thioredoxin reductase (TrxR), respectively. TrxR reduces the 12-kDa protein thioredoxin (Trx), which in turn provides elcctrons to ribonucleotide reductase, thioredoxin peroxidases (TPxs), certain transcription factors and other target molecules. Comparing the thioredoxin systems of different parasites and their respective host cells enhances our understanding of parasite biology and evolution, of parasite-host interactions and mechanisms of drug resistance. It furthermore opens avenues for the development of novel antiparasitic compounds. Here we review the current knowledge on the Trx systems of eukaryotic parasites, finally focusing on the malarial parasite Plasmodium falciparum.

Amino Acid Sequence↗

[Pathology of appendicitis].

Acute appendicitis represents one of the most common inflammatory diseases of the gastrointestinal tract. Acute appendicitis is most frequently based on the coincidence of obstruction, reduced blood supply, ischemic damage of the mucosa, and bacterial infection. Inflammation at other abdominal sites may also involve the appendix in 7% of cases causing periappendicitis. In 15-20% there are no pathologic findings of acute inflammation but rather post-inflammatory residues and a neuroma-like proliferation of Schwann cells, typically found in neurogenic appendicopathy. This finding may in part explain the clinical symptoms.

Acute Disease↗

The insulin gene VNTR polymorphism in Alzheimer's disease: results of a pilot study.

Insulin (INS) and insulin-like growth factors include different polypeptides involved in growth and development. Possibly they play a role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). A variable number of tandem repeats (VNTR) polymorphism at the human INS 5'-flanking region consisting of three distinct allele classes has been shown to influence the tissue-specific expression of INS and the insulin-like growth factor 2 (IGF-2). Since alterations in the expression of INS or IGF-2 might be relevant in AD, we investigated the association between the INS VNTR polymorphism and the risk for AD. We found no association between the INS VNTR genotype and the risk for AD (p = 0.873). However, survival analysis revealed that class III homozygotes of the INS VNTR polymorphism had an earlier initial onset in patients suffering from early AD (p = 0.002). Our preliminary results suggest, that genetically determined alterations of the INS/IGF-2 metabolism might modify the course of AD. Further studies are warranted to confirm these data in larger study samples.

Age of Onset↗

[Is there a temporal correlation between substance abuse and psychosis in adolescents?].

OBJECTIVES: The temporal relationship between substance abuse and symptoms of psychosis in adolescent patients was examined. METHODS: The hospital records of all adolescent inpatients admitted to the Central Institute of Mental Health in Mannheim during the period from 1976-1997 with a first-time diagnosis of psychosis were examined retrospectively for evidence of co-morbid substance abuse. RESULTS: In 18 of a total of 165 psychotic patients, co-morbid substance abuse was present, whose frequency rose after 1988, with a renewed increase since 1996. Two of the 18 adolescents began taking drugs only after the appearance of the first symptoms of psychosis, in 13 others the abuse was already well established, while for the final three patients the onset of psychotic symptoms and substance abuse was congruent, occurring within the same month. A close temporal correlation between symptoms of psychosis and substance abuse was established for amphetamines (including ecstasy), LSD and excessive abuse of cannabis. CONCLUSIONS: Substance abuse constitutes a risk factor for the development of psychoses without, however, necessarily being a direct trigger of psychosis.

Adolescent↗

[The Child Environment Survey].

The German Environmental Survey (GerES) is a representative population study conducted in Germany since the mid-1980s. GerES IV is the first survey for children only; it will be conducted in close connection with the Health Survey for Children and Adolescents on a random sample of 1,800 children (3 to 14 years of age) taken from the study population of the Health Survey for Children and Adolescents. Various parameters will be analysed in blood, urine, house dust, indoor air and tap water. They include neurotoxins (PCBs, Pb, Hg), carcinogenic/cocarcinogenic substances (PAHs, benzene, halocarbons, Cd, As), substances that may cause irritation of the respiratory tract, allergies and asthma (VOC, formaldehyde, house dust mite, mould fungi, pet allergens) and substances that may have an effect on metabolism with potentially long-term consequences (such as DEHP). An additional part was devoted to the link between hearing ability, noise and stress. A one-year pilot study on 550 children and adolescents was conducted in 2001 to 2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study.

Adolescent↗

A modified dot-blot method of protein determination applied in the tannin-protein precipitation assay to facilitate the evaluation of tannin activity in animal feeds.

Tannins have received considerable attention from animal nutritionists as potential agents for modifying ruminal fermentation patterns, or for exploring new feed resources. This group of secondary plant compounds is defined by their ability to form complexes with proteins. A widely accepted method for assaying the biological activity of extracted tannins is the precipitation of bovine serum albumin. The protein carries a radioactive label (125I) to allow direct quantification from the precipitate. Tannin-protein complexes dissolve in sodium dodecylsulfate solution. A dot-blot assay for protein determination, which is based on the reversible binding of a fluorochrome, benzoxanthene yellow, to the protein spots and is not disturbed by the presence of detergents, can replace the radioactive method by a fluorimetric measurement. A novel alternative to the last part of the dot-blot assay is to scan the stained protein spots in situ using a video camera and computer image analysis. Several filter sets were tested and, within a concentration range of 0.1-2.0 mg protein/ml, each of them yielded results identical to the original method while the time required was only 30 % of the working time consumed by the original procedure. The modified dot-blot assay should be applicable to the evaluation of tannin activity in all shrub and tree foliages considered as animal feed.

Animal Feed↗

A new animal model of femoral head necrosis induced by intraosseous injection of ethanol.

There is no reliable animal model of the early stages of osteonecrosis of the femoral head (ONFH) for the evaluation of new therapeutic approaches. In this study, we propose a new animal model of femoral head osteonecrosis. Pure ethanol was injected into the centre of the femoral head in adult Merino sheep under fluoroscopic control. After 3, 6 and 12 weeks the animals were killed and the femoral heads were harvested. Microradiographic and histological changes were analysed and recorded. Partial necrosis was documented over a period of 12 weeks in all animals. The appearance of necrosis in combination with intact macrotexture, macrocirculation and joint cartilage is similar to the features described in early ONFH in humans. Due to its efficacy and its similarity to the early stages of ONFH in humans, this model may be suitable to evaluate new therapeutic techniques in the treatment of ONFH.

Animals↗

A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline.

Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED(50) values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED(50) being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.

Aniline Compounds↗

Evidence for an unconventional magnetic instability in the spin-tetrahedra system Cu(2)Te(2)O(5)Br(2).

Thermodynamic experiments as well as Raman scattering have been used to study the magnetic instabilities in the spin-tetrahedra systems Cu(2)Te(2)O(5)X(2), X = Cl and Br. While the phase transition observed in the Cl system at T(N) = 18.2 K is consistent with 3D antiferromagnetic ordering, the phase transition at T(o) = 11.4 K in the Br system has several unusual features. We propose an explanation in terms of weakly coupled tetrahedra with a singlet-triplet gap and low-lying singlets.

Journal Article↗