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Biomedical subjects

J Kaufmann

Publications and source records attributed to J Kaufmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

13C NMR relaxation studies on cartilage and cartilage components.

We have investigated the molecular motions of polysaccharides of bovine nasal and pig articular cartilage by measuring the 13C NMR relaxation times (T1 and T2). Both types of cartilage differ significantly towards their collagen/glycosaminoglycan ratio, leading to different NMR spectra. As chondroitin sulfate is the main constituent of cartilage, aqueous solutions of related poly- and monosaccharides (N-acetylglucosamine and glucuronic acid) were also investigated. Although there are only slight differences in T1 relaxation of the mono- and the polysaccharides, T2 decreases about one order of magnitude, when glucuronic acid or N-acetylglucosamine and chondroitin sulfate are compared. It is concluded that the ring carbons are motion-restricted primarily by the embedment in the rigid pyranose structure and, thus, additional limitations of mobility do not more show a major effect. Significant differences were observed between bovine nasal and pig articular cartilage, resulting in a considerable line-broadening and a lower signal to noise ratio in the spectra of pig articular cartilage. This is most likely caused by the higher collagen content of articular cartilage in comparison to the polysaccharide-rich bovine nasal cartilage.

Acetylglucosamine↗
PubMed2000

The initiator element of the Drosophila beta2 tubulin gene core promoter contributes to gene expression in vivo but is not required for male germ-cell specific expression.

The tissue-specific expression of the Drosophila beta 2 tubulin gene ( B2t ) is accomplished by the action of a 14-bp activator element (beta2UE1) in combination with certain regulatory elements of the TATA-less, Inr-containing B2t core promoter. We performed an in vivo analysis of the Inr element function in the B2t core promoter using a transgenic approach. Our experiments demonstrate that the Inr element acts as a functional cis -regulatory element in vivo and quantitatively regulates tissue-specific reporter expression in transgenic animals. However, our mutational analysis of the Inr element demonstrates no essential role of the Inr in mediating tissue specificity of the B2t promoter. In addition, a downstream element seems to affect promoter activity in combination with the Inr. In summary, our data show for the first time the functionality of the Inr element in an in vivo background situation in Drosophila.

Animals↗
PubMed2000

Atypical organisation of the auditory cortex in dyslexia as revealed by MEG.

Neuroanatomical and -radiological studies have converged to suggest an atypical organisation in the temporal bank of the left-hemispheric Sylvian fissure for dyslexia. Against the background of this finding, we applied high temporal resolution magnetoencephalography (MEG) to investigate functional aspects of the left-hemispheric auditory cortex in 11 right-handed dyslexic children (aged 8-13 years) and nine matched normal subjects (aged 8-14 years). Event-related field components during a passive oddball paradigm with pure tones and consonant-vowel syllables were evaluated. The first major peak of the auditory evoked response, the M80, showed identical topographical distributions in both groups. In contrast, the generating brain structures of the later M210 component were located more anterior to the earlier response in children with dyslexia only. Control children exhibited the expected activation of more posterior source locations of the component that appeared later in the processing stream. Since the group difference in the relative location of the M210 source seemed to be independent of stimulus category, it is concluded that dyslexics and normally literate children differ as to the organisation of their left-hemispheric auditory cortex.

Adolescent↗
PubMed1999

Molecular dynamics of a tetrasaccharide subunit of chondroitin 4-sulfate in water.

Molecular dynamics (MD) simulations on a tetrasaccharide subunit of chondroitin 4-sulfate (CS4) in aqueous solution were carried out to study its interactions with water. Pair distribution functions and diffusion coefficients were calculated from a 4 ns trajectory and the hydration of different molecular groups was analysed. The average values of the interglycosidic torsion angles found in the simulations are phi 13 = -10 degrees, psi 13 = -85 degrees and phi 13 = 80 degrees, psi 13 = 90 degrees for the beta-(1-->3) linkage, and phi 14 = -10 degrees, psi 14 = -70 degrees for the beta-(1-->4) linkage. Hydrophobic patches formed by sugar ring CH groups were found. The diffusion coefficients of the water molecules vary from 1.4 x 10(-9) to 2.3 x 10(-9) m2 s-1 depending on the distances between the water molecules and the atoms of the CS4 molecule and the type of CS4 atoms, respectively. Reorientation correlation times of the water molecules in the vicinity of different CS4 atoms were estimated to be about 1 ps at a polymer concentration of 4 wt.% CS4. The number of hydrogen bonds between the water molecules and the acceptor atoms of CS4 was determined to be about 20 per disaccharide unit, indicating a higher hydration ability of chondroitin sulfate in comparison with non-sulfated oligosaccharides. Substructures, where water molecules are involved in hydrogen bonds to different sugar rings, were found, which may be important for the stabilisation of the secondary structure of the CS4 molecule.

Carbohydrate Conformation↗
PubMed1999

Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement.

UNLABELLED: We assessed the analgesic efficacy of postoperative epidural ropivacaine 0.1% with and without sufentanil 1 microgram/mL in this prospective, randomized, single-blinded study of 30 ASA physical status I-III patients undergoing elective total hip replacement. Lumbar epidural block using 0.75% ropivacaine was combined with either propofol sedation or general anesthesia for surgery. After surgery, the epidural infusion was commenced. Fifteen patients in each group received either an epidural infusion of 0.1% ropivacaine with 1 microgram/mL sufentanil (R + S) or 0.1% ropivacaine without sufentanil (R) at a rate of 5-9 mL/h. All patients had access to i.v. piritramide via a patient-controlled analgesia device. The R + S group consumed six times less piritramide over a 48-h infusion period than the R group (median 12.7 vs 73.0 mg; P < 0.001). Motor block was negligible for the study duration in both groups. Patient satisfaction was excellent. The incidence of adverse events, such as nausea, was similar. We conclude that a continuous epidural infusion of 0.1% ropivacaine with 1 microgram/mL sufentanil is more effective than ropivacaine alone in treating pain after elective hip replacement without motor block. IMPLICATIONS: This is the first randomized study comparing the efficacy of the epidural combination of ropivacaine 0.1% and sufentanil 1 microgram/mL versus plain ropivacaine 0.1% in treating pain after hip replacement. We found that ropivacaine 0.1% and sufentanil 1 microgram/mL led to a sixfold reduction in opioid requirements after total hip replacement by producing a negligible motor block.

Adult↗
PubMed1999

Human transcription factor hTAF(II)150 (CIF150) is involved in transcriptional regulation of cell cycle progression.

Here we present evidence that CIF150 (hTAF(II)150), the human homolog of Drosophila TAF(II)150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAF(II)150) seems to be less tightly associated with human transcription factor IID than hTAF(II)130 is associated with hTAF(II)250. The transient functional knockout of CIF150 (hTAF(II)150) protein led to cell cycle arrest at the G(2)/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAF(II)150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAF(II)150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAF(II)150) function. We defined a CIF150 (hTAF(II)150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAF(II)150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression.

Cell Cycle↗
PubMed1999

A new method of measuring C-reactive protein, with a low limit of detection, suitable for risk assessment of coronary heart disease.

A new indication has been proposed for C-reactive protein (CRP) as a prognostic risk marker of coronary heart disease (CHD). The new indication calls for accurate (true and precise) measurement of CRP within the conventional reference range (< 5 mg/L). The existing turbidimetric and nephelometric methods do not cover the required measuring range and thus time-consuming and labour-intensive enzyme immunoassays have been used for the clinical studies focusing on CHD risk. We developed a new method based on microparticle enhanced turbidimetry, which attained the required limit of detection, while keeping the upper measuring limit comparable to the existing turbidimetric and nephelometric methods. The superior characteristics of the new method were realised by mixing two types of microparticle reagents differing in microparticle size and reactivity of coated antibody. The analytical detection limit of the method was 0.28 mg/L with use of only 2.5 microliters serum. The method showed good precision at 2 to 3 mg/L, the critical concentration range for CHD risk assessment. Other performance data including dilution linearity, method comparison, and interference study also met the requirements for the practical use in the clinical laboratories. Sera from 354 apparently healthy blood donors were measured in a reference range study. The reference range estimated after log-transformation was 0.16 mg/L to 7.57 mg/L CRP, with a total range of 0.09 mg/L to 21.0 mg/L. The distribution of CRP concentrations in this population was comparable to other results that established the use of CRP as a risk marker of CHD in a prospective study.

Antibodies, Monoclonal↗
PubMed1998

Development of a new microparticle-enhanced turbidimetric assay for C-reactive protein with superior features in analytical sensitivity and dynamic range.

Novel assay techniques were applied to a newly developed microparticle-based assay for C-reactive protein (CRP). By using two different sized microparticles covalently coated with two monoclonal antibodies of different reactivity, high analytical sensitivity and a high upper measuring limit could be simultaneously attained, resulting in a remarkably wide dynamic range. This range was further increased by calculating the signal (reaction rate) optimally with a new software capability of COBAS INTEGRA, a clinical chemistry analyzer. The assay showed high precision between 2 mg/l and 160 mg/l with use of only 2.5 microl specimen. The detection limit was estimated as 0.3 mg/l CRP. The assay was four to eight times more sensitive and precise than existing turbidimetric or nephelometric assays with comparable upper measuring limits. The assay also showed good linearity and correlated well with commercial assays. This new microparticle-based CRP assay provides the accuracy and precision that are required to determine CRP at low concentrations where new clinical implications such as prognosis of cardiovascular diseases are envisaged. The assay's wide dynamic range will additionally lead to a reduction in the number of repeated analyses, thus improving the efficiency of CRP determinations in clinical laboratories.

Angina Pectoris↗
PubMed1998

[Concomitant dermatitis herpetiformis Duhring, arthritis and Sjögren syndrome in a patient with celiac disease].

We report on a 26 year old woman with dermatitis herpetiformis Duhring, diagnosed at 10 years of age, who developed arthritis, symptoms of celiac disease, and Sjögren's syndrome 15 years later. Clinical symptoms, biopsies of duodenal mucosa and salivary glands as well as serological findings established the diagnoses. A coincidence of these pathologies has not been reported before. Gluten-free diet alleviated severity of clinical symptoms very quickly indicating the basic pathology of celiac enteropathy in the immunological disorders.

Adult↗
PubMed1998

CIF150, a human cofactor for transcription factor IID-dependent initiator function.

The transcription factor IID (TFIID) complex is highly conserved between the Drosophila and mammalian systems. A mammalian homolog has been described for all the Drosophila TATA box-binding protein-associated factors (TAFs), with the exception of dTAF(II)150. We previously reported the identification of CIF, an essential cofactor for TFIID-dependent transcription from promoters containing initiator (Inr) elements. Here we describe the molecular cloning of CIF150, the human homolog of dTAF(II)150, and present biochemical evidence that this factor is involved in Inr activity. CIF150 is capable of mediating TFIID-dependent Inr activity in a complementation assay, and a protein fraction lacking Inr activity lacks detectable amounts of CIF150. Despite the striking similarity to dTAF(II)150, CIF150 does not appear to be associated with human TFIID. However, in vitro binding assays revealed a specific and direct interaction between CIF150 and hTAF(II)135. This interaction might be structurally important for the functional interaction between CIF150 and human TFIID, since CIF150 stabilizes TFIID binding to a core promoter.

Amino Acid Sequence↗
PubMed1998

[Swiss veterinary research and development project in the Gambia: the point of view of the breeder concerning control of helminthiasis in livestock].

The epidemiology of nematodes in livestock in The Gambia was assessed. A prophylactic biannual treatment was then tested on cattle and sheep. This treatment resulted in a significant improvement in the reproductive performances (sheep: lambings/year increasing from 1.04 to 1.22 and lambs/lambing increasing from 1.11 to 1.19; cattle: age at first calving decreasing from 58 to 50 months) and, in cattle, a significant improvement of the weight (varying between 8% and 17% in 1 to 4 year old animals). A socioeconomic study conducted in parallel showed that the treatment in cattle is on average profitable (benefit/cost ratio of 1.14) but remains a risky investment which should not be generalised (benefit/cost ratio would have been below 1 in more than half of the participating herds). In sheep, the benefit/cost ratio is high (2.47) with a low risk of losses (< 10%). The obstacles to the adoption by farmers of such a treatment and the usefulness of a pluridisciplinary approach in similar studies are then discussed.

Animals↗
PubMed1997

Effect of strategic gastrointestinal nematode control on fertility and mortality of N'Dama cattle in The Gambia.

A large-scale longitudinal study was undertaken to investigate the effects of a strategic treatment of gastrointestinal nematodes on the mortality and fertility of N'Dama cattle under village conditions. Initially, 1046 animals from 26 private N'Dama cattle herds, were monitored from October 1989 to December 1994. Each herd was stratified by age and the animals were randomly allocated to two groups with a similar average age. One group received a single anthelmintic treatment of fenbendazole (Panacur, 7.5 mg/kg BW, Hoechst Veterinä AG) in October 1989, whereas the other group remained untreated. In July 1990, the herds were subdivided into two different treatment schemes. In the herds of scheme 1, the treated animals (Treatment group I) were treated once (in August), whereas in the herds of scheme 2, the treated animals (Treatment group II) were treated twice (in July and September). The same treatment schedule was used in the subsequent rainy seasons until December 1994. One group in every herd of both schemes served as control (Treatment group 0) and received no anthelmintic treatment throughout the study. The average annual cumulative incidence mortality between 0-1 year was more than two times higher in treated animals compared to their controls (21% against 7.5%). No differences were found in older age categories. Survival analysis confirmed differences in mortality from 0-1 year, but were not significant in proportional hazard models. The 25% quantiles of age at first calving was used to quantify differences between twice treated animals (50.2 months) and its controls (58.3 months) which represents a decrease of 8 months in twice treated animals. Annual calving rates of twice treated animals were 52.2% compared to 43.6% in the control group (P < 0.001), which is an increase of 8.6% to the control rate. Possible causes of increased mortality in 0-1 year old treated calves are discussed. We can conclude that in the present epidemiological situation and the given parasite spectrum, gastro-intestinal nematodes mainly affect host fertility. Strategic control of gastro-intestinal nematodes is thus recommended for young heifers up to their age of first calving provided the overall financial analysis of the intervention is beneficial.

Abortion, Veterinary↗
PubMed1997

Effect of strategic gastrointestinal nematode control on growth of N'Dama cattle in Gambia.

From October 1989 to December 1994, a longitudinal study on the control of gastrointestinal nematodes was done on 1000 N'Dama cattle in 20 private herds in Gambia. Each herd was divided into two groups with an even distribution of age and sex. One group received a single anthelmintic treatment of Fenbendazole, Panacur Hoechst Veterinär GmbH, 7.5 mg kg-1 BW in October 1989, whereas the other group served as an untreated control. In July 1990, the herds were subdivided into two different treatment schemes. In the herds of the first scheme the treated animals (Treatment group I) were treated once (in August), whereas in the herds of the second scheme the treated animals (Treatment group II) were treated twice (in July and September). The same treatment schedule was used in the subsequent rainy seasons until December 1994. One group in every herd served as control (Treatment group 0) and received no anthelmintic treatment throughout the study. One annual fenbendazole treatment had no significant effect on liveweights, whereas two annual treatments significantly increased liveweights of the age group 12-24 and 24-36 months by 9.4%, and 17.5%, respectively. Animals less than 12 months old had 6.3% higher liveweights after two treatments, the difference was statistically not significant (P < 0.06). Average weights of 3- and 4-year-old, twice-treated animals were 13.1% and 8.2%, respectively, higher compared with their controls. No effect of anthelminthic treatment on liveweights was found in 5-year-old and older animals. Herd structure analysis demonstrated that overall male offtake rates ranged from 12 to 28% in the 3-, 4- and 5-year-old age categories. The age categories within which deworming improves liveweights thus coincides with the age at which males are mainly sold. These results suggest that biannual metaphylactic treatments (end of July and beginning of September) of all animals from birth to an age of 4 years should be recommended, provided that the financial analysis demonstrates the profitability of this intervention.

Animals↗
PubMed1996

CIF, an essential cofactor for TFIID-dependent initiator function.

The core promoters for mammalian protein-coding genes often contain a TATA box, an initiator (Inr) element, or both of these control elements. The TFIID complex is essential both for TATA activity and for the activity of a common class of Inr elements characterized by an approximate consensus sequence PyPyA+1NT/APyPy. Although the complete set of proteins required for basal TATA-mediated transcription has been established, the requirements for TFIID-dependent Inr activity remain undefined. In this study we set out to reconstitute Inr activity with purified and recombinant general transcription factors. For this analysis, Inr activity was measured as the ability of an Inr to enhance the strength of a core promoter containing an upstream TATA box. Inr activity was not detected in reactions containing TFIIB, RAP30, RAP74, RNA polymerase II, and either TBP or TFIID, even though these factors were sufficient for TATA-mediated transcription from supercoiled templates. By use of a complementation assay, a factor that imparts Inr activity was identified. This factor, named CIF, stimulated Inr activity in reactions containing the TFIID complex, but activity was not detected with TBP. Further characterization of CIF suggested that it contains multiple components. Functional and immunological experiments demonstrated that one of the CIF components is the mammalian homolog of Drosophila TAF(II)150, which is not tightly associated with mammalian TFIID. These results reveal significant differences in the factor requirements for basal TATA and Inr activity. Further elucidation of these differences is likely to explain the need for the core promoter heterogeneity found within protein-coding genes.

Animals↗
PubMed1995

Effect of herd management on the contamination of night holding areas (correos) and infections with gastrointestinal nematodes of N'Dama cattle in The Gambia.

The densities of infective nematode larvae (L3/m2) in the night holding places (locally called "correos") of 2 traditionally kept N'Dama herds were estimated at weekly intervals throughout an entire rainy season. Herd 1 moved correos every 3 weeks whereas herd 2 remained in the same area for most of the rainy season. Removal to a new correo was invariably accompanied by a drastic drop of L3/m2. Conversely, L3/m2 increased rapidly up to values of more than 1,000 when the herds used the same night holding place for more than 3 weeks. Calves kept in herds with frequent changes of the correo showed significantly lower nematode egg counts and higher growth rates during the rainy season, combined with a reduced weight loss during the following dry season. The results of this study indicate that a regular frequent change of the correo is an effective method of reducing nematode infection risk and increasing calf growth and that this might be a sustainable part of an integrated strategic programme to control gastrointestinal nematode infections wherever correos are used.

Animal Husbandry↗