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K Becker

Publications and source records attributed to K Becker.

At least 55 records · Page 3Linked to original sources
PubMed2004

Hyperekplexia and stiff-man syndrome: abnormal brainstem reflexes suggest a physiological relationship.

BACKGROUND AND OBJECTIVES: Hyperekplexia and the stiff-man syndrome (SMS) are both conditions with exaggerated startle suggesting abnormal brainstem function. Investigation of brainstem reflexes may provide insight into disturbed reflex excitation and inhibition underlying these movement disorders. PATIENTS AND METHODS: Using four-channel EMG, we examined four trigeminal brainstem reflexes (monosynaptic masseter, masseter inhibitory, glabella, and orbicularis oculi blink reflexes) and their spread into pericranial muscles in five patients with familial hyperekplexia (FH), two with acquired hyperekplexia (AH), 10 with SMS, and 15 healthy control subjects. RESULTS: Both FH/AH and SMS patients had abnormal propagation of brainstem reflexes into pericranial muscles. All patients with hyperekplexia showed an abnormal short-latency (15-20 ms) reflex in the trapezius muscle with a characteristic clinical appearance ("head retraction jerk") evoked by tactile or electrical stimulation of the trigeminal nerve, but normal monosynaptic masseter reflexes. Inhibitory brainstem reflexes were attenuated in some FH/AH patients. Four of 10 patients with SMS had similar short-latency reflexes in the neck muscles and frequently showed widespread enhancement of other excitatory reflexes, reflex spasms, and attenuation of inhibitory brainstem reflexes. CONCLUSION: Reflex excitation is exaggerated and inhibition is attenuated in both stiff-man syndrome and familial or acquired hyperekplexia, indicating a physiological relationship. Reflex transmission in the brainstem appears biased towards excitation which may imply dysfunction of inhibitory glycinergic or GABAergic interneurons, or both.

Adolescent↗
PubMed2004

[Prediction of response to neoadjuvant chemotherapy in Barrett's carcinoma by quantitative gene expression analysis].

The potential of gene expression profiles to predict the response to neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the esophagus was analyzed. Paraffin-embedded endoscopic esophageal tumor biopsies of 38 patients with advanced esophageal adenocarcinoma (Barrett's adenocarcinoma) were included. All patients underwent two cycles of cisplatin and fluorouracil (5-FU) therapy with or without additional paclitaxel (taxol) followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU-metabolism associated genes thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), MAP7, ELF3, as well as of platinum and taxane associated related genes caldesmon, excision cross-complementing genes (ERCC1 and ERCC4) HER2-neu, DNA damage-inducible gene 45 (GADD45) and multidrug resistance genes (MDR1, MRP1) were determined using real-time RT-PCR. Expression levels were correlated with the histopathological response to chemotherapy assessed in surgically resected specimens. Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (p = 0.012), Caldesmon (p = 0.016), MRP1 (p = 0.007) and MDR1 (p = 0.025). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (p = 0.013 and p = 0.015, respectively). Additionally, intratumoral heterogeneity of gene expression of selected genes (TP, DPD, MTHFR, HER2-neu, Caldesmon, ERCC4, MRP1) was additionally verified in 9 untreated Barrett's adenocarcinoma by examination of 5 distinct tumor areas and was observed in 12.7% (5.6%-23.5%, CI 95%) of all cases analyzed. Our results indicate that determination of mRNA levels of a few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with advanced adenocarcinoma of the esophagus.

Adenocarcinoma↗
PubMed2003

Spinal inhibitory synaptic transmission in the glycine receptor mouse mutant spastic.

Inhibitory glycine receptor (GlyR) and GABA(A) receptor (GABA(A)R)-mediated synaptic transmission was examined in two strains of the GlyR mutant mouse spastic and the respective wild types. The mutants display a mild and a severe neurological phenotype. Electrically evoked postsynaptic whole-cell currents were recorded from alpha-motoneurons in lumbar spinal cord slices. Amplitudes of GlyR-mediated IPSCs were significantly reduced in the severe phenotype in comparison to the respective wild type and the mild phenotype mutants. Surprisingly, amplitudes of GABA(A)R-mediated IPSCs were also significantly reduced in both mutants. Fast time constants of the decay phase of IPSCs were slightly reduced for the GlyR-mediated IPSCs and significantly larger for the GABA(A)R-mediated IPSCs in both mutant strains.

Animals↗
PubMed2003

Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development.

The malarial parasite Plasmodium falciparum is known to be sensitive to oxidative stress, and thus the antioxidant enzyme glutathione reductase (GR; NADPH+GSSG+H(+) <==> NADP(+)+2 GSH) has become an attractive drug target for antimalarial drug development. Here, we report the 2.6A resolution crystal structure of P.falciparum GR. The homodimeric flavoenzyme is compared to the related human GR with focus on structural aspects relevant for drug design. The most pronounced differences between the two enzymes concern the shape and electrostatics of a large (450A(3)) cavity at the dimer interface. This cavity binds numerous non-competitive inhibitors and is a target for selective drug design. A 34-residue insertion specific for the GRs of malarial parasites shows no density, implying that it is disordered. The precise location of this insertion along the sequence allows us to explain the deleterious effects of a mutant in this region and suggests new functional studies. To complement the structural comparisons, we report the relative susceptibility of human and plasmodial GRs to a series of tricyclic inhibitors as well as to peptides designed to interfere with protein folding and dimerization. Enzyme-kinetic studies on GRs from chloroquine-resistant and chloroquine-sensitive parasite strains were performed and indicate that the structure reported here represents GR of P.falciparum strains in general and thus is a highly relevant target for drug development.

Amino Acid Sequence↗
PubMed2003

Hydrothermal recharge and discharge across 50 km guided by seamounts on a young ridge flank.

Hydrothermal circulation within the sea floor, through lithosphere older than one million years (Myr), is responsible for 30% of the energy released from plate cooling, and for 70% of the global heat flow anomaly (the difference between observed thermal output and that predicted by conductive cooling models). Hydrothermal fluids remove significant amounts of heat from the oceanic lithosphere for plates typically up to about 65 Myr old. But in view of the relatively impermeable sediments that cover most ridge flanks, it has been difficult to explain how these fluids transport heat from the crust to the ocean. Here we present results of swath mapping, heat flow, geochemistry and seismic surveys from the young eastern flank of the Juan de Fuca ridge, which show that isolated basement outcrops penetrating through thick sediments guide hydrothermal discharge and recharge between sites separated by more than 50 km. Our analyses reveal distinct thermal patterns at the sea floor adjacent to recharging and discharging outcrops. We find that such a circulation through basement outcrops can be sustained in a setting of pressure differences and crustal properties as reported in independent observations and modelling studies.

Journal Article↗
PubMed2003

Molecular prenatal diagnosis in a case of an X-linked dominant chondrodysplasia punctata.

X-linked dominant chondrodysplasia punctata, (CDPX2-MIM302960) also known as Conradi-Hünermann-Happle syndrome, is a rare form of skeletal dysplasia that affects the skeleton, skin, hair, and eyes. The disorder is caused by mutations within the emopamil binding protein (Ebp) that functions as a delta(8), delta(7) sterol isomerase in the cholesterol biosynthesis pathway. To date, over 40 separate mutations have been reported in the Ebp gene, EBP, with no obvious correlation between the molecular defects and the severity of the clinical phenotype. We have studied a 30-year-old woman who presented in adulthood with skin, hair, and mild skeletal defects but no ocular abnormalities and have identified a heterozygous missense mutation within the third transmembrane domain of the protein. In addition, we have performed molecular prenatal testing on her unborn fetus. The results demonstrate inter-familial variability for missense mutations within the emopamil binding protein and add to the molecular data for CDPX2.

Adult↗
PubMed2003

["Body and soul and friendships destroyed". Behavior therapy of a 14-year-old adolescent with alcohol dependence syndrome].

OBJECTIVES: About 250,000 children and adolescents in Germany are dependent upon alcohol or at severe risk of developing an alcohol disorder. Whereas adults who abuse alcohol benefit from a variety of therapy manuals and numerous institutions offering long-term disorder-specific care, the situation with regard to adolescent patients needs to be upgraded. METHODS: We present the behavioral therapy of an alcohol-dependent 14-year-old boy, focusing on a version of Petry's therapy manual for alcoholism (1996) that has been adapted for the treatment of adolescents. The efficacy of worksheets as a supplement to the usual behavior therapy, or social or family interventions in the treatment of alcohol-dependent adolescents is discussed.

Acting Out↗
PubMed2003

[Comorbidity of compulsive disorders in childhood and adolescence].

OBJECTIVE: The cross-sectional comorbidity of child and adolescent inpatients with obsessive-compulsive disorder (OCD) was assessed. METHODS: The hospital records of all inpatients treated for OCD since 1976 (31 girls, 46 boys) were compared with data from a prospective epidemiological longitudinal study (90 girls, 84 boys) in two age cohorts (< 15 years; > or = 15 years) with regard to comorbid psychiatric diagnoses. Additionally, psychiatric Axis I diagnoses of patients with a supplementary diagnosis of compulsive symptoms (n = 45) were descriptively assessed in the client population. RESULTS: In the subgroup of OCD patients < 15 years, boys showed a higher incidence of tic disorders. OCD girls > or = 15 years showed a tendency toward more frequent comorbid affective disorders and a significant result regarding concurrent eating disorders. Eighteen of 27 female patients with supplementary compulsive symptoms requiring clinical intervention had an Axis I diagnosis of eating disorder. CONCLUSIONS: Due to different criteria of classification, diverging definitions of comorbidity and different age cohorts and samples, studies on comorbidity in OCD patients are difficult to compare. The frequency of comorbid psychiatric disorders may be over-estimated if the general prevalence of psychiatric disorders in terms of gender and age is not taken into account.

Adolescent↗
PubMed2003

Identification of two novel nonsense mutations in the transglutaminase 1 gene in a Hungarian patient with congenital ichthyosiform erythroderma.

Congenital ichthyosiform erythroderma (CIE) belongs together with lamellar ichthyosis (LI) to the group of autosomal recessive congenital ichthyoses (ARCI). Mutations in the transglutaminase (TGase) 1 gene (TGM1) have been identified in several families with LI and in some families with CIE. We report a case of CIE with two new nonsense mutations: a C7780G transversion in exon 11 resulting in a premature stop codon at aminoacid residue Y503X and a C8533G transversion in exon 13 leading to a nonsense mutation at S669X. These mutations were also identified in a heterozygous pattern in the unaffected parents. These two termination-codons result in the translation of a truncated protein at the C-terminal end domain of the TGM 1 molecule. B.C1 monoclonal antibody failed to detect TGase 1 in the patient's skin sample, and TGase activity measured by monodansyl cadaverine-incorporation showed the reduced TGase activity at the distribution of TGase 1 in the epidermis.

Child↗
PubMed2003

An outbreak of candidemia due to Candida tropicalis in a neonatal intensive care unit.

An outbreak of candidemia due to Candida tropicalis involving 16 neonates (gestational age 28-36 weeks) is reported. All infants had received hyperalimentation and at least one course of antibiotics. The commonest clinical manifestations included episodes of acute respiratory distress and lack of response to antibacterial antibiotic therapy. Candida tropicalis was recovered from blood in all the 16 infants and urine cultures were positive in 14 infants. Environmental sampling yielded C. tropicalis from one each of the blankets and mattresses used for neonates. Four of five urinary tract isolates and both environmental isolates genotyped by arbitrarily primed-PCR with several random primers were shown to belong to the same genotype.

Antifungal Agents↗
PubMed2003

Oropharyngeal carriage of Candida species in HIV-infected patients in India.

The present investigation represents the first study of oropharyngeal carriage of Candida and other yeasts in HIV-infected patients in India. One hundred and fifty HIV-positive patients were investigated by culturing their swish samples on plates of CHROMagar Candida. Ninety-eight patients (65.3%) were positive for Candida and four (2.7%) were positive for other yeasts. Among them, the first Indian C. dubliniensis isolate has been recovered. Molecular typing of selected C. albicans isolates by AP-PCR revealed two major genotypes based on the banding patterns. The susceptibilities of 30 Candida isolates to five antifungal agents including the new triazole voriconazole were determined in a micro-dilution test, according to the NCCLS protocol M 27. All the 22 C. albicans isolates were susceptible to five antimycotic agents (flucytosine, amphotericin B, fluconazole, voriconazole and itraconazole) except one isolate (VPCI-122), which was resistant to flucytosine (MIC > or = 64 mg l-1). The azole-resistant isolates reported here endorse the role of antifungal susceptibility testing whenever antifungal treatment with azoles is planned.

AIDS-Related Opportunistic Infections↗
PubMed2003

Supplementation of barley straw with Sesbania pachycarpa leaves in vitro: effects on fermentation variables and rumen microbial population structure quantified by ribosomal RNA-targeted probes.

Tropical livestock is often maintained on roughage-based diets deficient in N, and therefore requires supplementation with protein-rich substrates to achieve reasonable production levels. The optimum inclusion rate of a potential supplement is usually determined by in vivo feeding trials or by in vitro incubation of the diet components to estimate the feed value of the complete diet. The present work simulates a supplementation experiment in vitro, by incubating a pure roughage (barley straw), a pure supplement (Sesbania pachycarpa leaves) and mixtures of the two, with increasing inclusion levels of the supplement, in a short-term batch incubation system. Fermentation kinetics were followed by the release of fermentation endproducts (gas and short-chain fatty acids). Microbial biomass was estimated using ribosomal (r) RNA as internal marker for bacteria and eukaryotes separately. Cell-wall-degrading subpopulations were quantified by hybridisation with taxon-specific oligonucleotide probes targeting Chytridiomycetes, Fibrobacter spp., Ruminococcus albus and R. flavefaciens. Carboxymethylcellulase (CMCase) was assayed as an indicator for cell-wall-degrading activity. The addition of S. pachycarpa leaves stimulated fermentation in all cases. Gas production, and especially rRNA concentration, showed clear maxima at 40 % S. pachycarpa inclusion, rates that significantly exceeded the values interpolated from the incubations of the pure substrates. Short-chain fatty acid yield changed only slightly, but in the same way. The analysis of the microbial population structure showed that the positive effects were mainly mediated through enhanced growth of Ruminococcus spp. Increasing proportions of S. pachycarpa leaves in the diet led to a drastic decline in the total eukaryotic population. This points to a defaunation, which may also have added to the positive effects. The eukaryotic subpopulation of the rumen fungi were affected to a lesser degree. Although the cell-wall-degrading organisms showed positive responses to the supplementation, the CMCase activity was not affected significantly by the supplementation. The present work shows that it is possible to predict optimum inclusion levels for a new feed supplement in vitro and thus reduce in vivo experiments. It was also demonstrated that true supplementation effects occur particularly for the microbial biomass production, which is the primary source of amino acids for the ruminant animal. The analysis of microbial population structure in context with conventional metabolic measurements adds valuable information to interpret the observed effects on production-related variables.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Effects of Moringa oleifera seed extract on rumen fermentation in vitro.

Moringa oleifera is a pantropical tree of the family Moringaceae. A previously undescribed property of an aqueous extract from the seeds of this plant is the modulation of ruminal fermentation patterns, especially protein degradation, as demonstrated in a short-term batch incubation system. Gas, short chain fatty acids (SCFA) and cellulolytic enzyme activities were determined as general fermentation parameters. A dot blot assay able to directly detect true protein in rumen fluid samples was used to quantify protein degradation. For complex substrates the interpretation of protein degradation profiles was amended by polyacrylamide gel electrophoresis (PAGE) of the samples. When incubated with pure carbohydrates at a concentration of 1 mg ml(-1), the extract reduced microbial degradation of the model protein, bovine serum albumin (BSA), such that its concentration was at least 40% above the control after 12 h of incubation. Total protein degradation was thus delayed by approximately 9 h. When fermented along with wheat straw, leaf protein (Rubisco) was almost entirely protected during 12 h of fermentation. The degradation of soy proteins was retarded by at least 4-6 h, depending on the protein band. There were strong side effects on the fermentation of pure cellulose (SCFA yield-60% after 12 h), whereas cellobiose and starch fermentation were less affected (-18 and -8%, respectively). When the complex substrates were fermented, SCFA yield was reduced by approximately 30% after 12 h. In our work we clearly demonstrate the efficacy of the new substance, which is neither a tannin nor a saponin, in an in vitro system, using pure as well as complex substrates. The properties shown in vitro for the crude extract suggest that it could have a positive effect on the protein metabolism of ruminants under intensive management and that negative side effects can be overcome by an optimized dosage. If the chemical nature of the active substance and its mechanism of action can be clarified, it may provide an alternative to replace critical synthetic feed additives (such as antibiotics) for high yielding dairy cows.

Animals↗
PubMed2003

Feeding level and diet quality influence trophic shift of C and N isotopes in Nile tilapia (Oreochromis niloticus (L.)).

Many scientists use naturally occurring stable isotopes to reconstruct the diets of animals. However, isotopic ratios may be affected not only by the composition of the diet but also by the amount of food consumed. Thus, an experiment using tilapia (Oreochromis niloticus) was carried out to test the influence of feeding level on delta13C and delta15N of fish given a semi-synthetic wheat gluten/wheat starch based diet. In addition, the effect of diet quality was tested by comparing tilapia given this feed with tilapia fed a fish meal/wheat meal based diet. Forty-four tilapia were reared individually. After a prefeeding phase, fish were randomly assigned to five groups, four on the semi-synthetic diet at different feeding levels and one group on the fish meal/wheat meal based diet fed at the equivalent of the highest level of the semi-synthetic diet. The experiment lasted eight weeks. Proximate composition, gross energy content and delta13C and delta15N values were determined in feed and fish, for delta13C separately in the lipids and the lipid-free matter. Delta13C in the lipids and the lipid-free matter and delta15N of tilapia fed the semi-synthetic diet decreased significantly with increasing feeding rate. The absolute values of the trophic shift in fish fed the semi-synthetic wheat based diet were significantly higher than in fish fed the fish meal/wheat meal based diet. The different delta13C and delta15N values in tilapia fed the same diet at different feeding levels and the influence of feed quality on the trophic shift add to the uncertainty involved in the use of stable isotopes in ecological research.

Animal Feed↗
PubMed2003

Effect of different lipid extraction methods on delta13C of lipid and lipid-free fractions of fish and different fish feeds.

For many ecological applications of stable carbon isotope techniques, it is necessary to separate the lipid and lipid-free fractions. The effect of different lipid extraction methods on the isotope signature of the remaining lipid-free matter as well as the lipid fraction was tested. A hot extraction form of the Soxhlet method using petrol-ether was compared with two liquid-liquid extraction methods for lipid determination described by Bligh and Dyer and Smedes. Solid samples of fish and different natural food items were subjected to extraction and the carbon isotope ratios in lipid and lipid-free matter determined by IRMS. All methods were suitable for lipid extraction from all samples analysed here and did not cause biologically relevant differences (> 1%) in carbon isotopic ratios, except the Bligh and Dyer extraction method using chloroform which caused systematic errors for delta13C when applied to diatoms.

Animal Feed↗
PubMed2003

Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes.

Astrocytes may be infected with the human immunodeficiency virus type 1 (HIV-1) or exposed to the HIV protein gp120, yet their role in the pathogenesis of HIV dementia is largely unknown. To characterize the effects of HIV on astrocytic transcription, microarray analysis and ribonuclease protection assays (RPA) were performed. Infection of astrocytes by HIV or treatment with gp120 had differential and profound effects on gene transcription. Of the 1153 oligonucleotides on the immune-based array, the expression of 108 genes (53 up; 55 down) and 82 genes (32 up; 50 down) were significantly modulated by gp120 and HIV infection respectively. Of the 1153 oligonucleotides on the neuro-based array, 58 genes (25 up; 33 down) and 47 genes (17 up; 30 down) were significantly modulated by gp120 and HIV infection respectively. Chemokine and cytokine induction occurred predominantly by HIV infection, whereas gp120 had no significant effect. These results were confirmed by RPA. The authors conclude that profound alterations of astrocytic function occur in response to HIV infection or interaction with viral proteins, suggesting that astrocytes may play an important role in the pathogenesis of HIV dementia.

AIDS Dementia Complex↗