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Biomedical subjects

E Werner

Publications and source records attributed to E Werner.

At least 55 records · Page 3Linked to original sources

Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical preparation.

Only few data are available on intestinal calcium absorption from foodstuffs and composite meals in humans. The aim of the study was to compare intraindividually the calcium absorption from milk and from a breakfast with that from a pharmaceutical calcium preparation of equal calcium content. In 8 healthy volunteers between 44 and 58 years of age, the intestinal calcium absorption was measured in randomized order applying the double isotope technique from: (1) 500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg 42Ca in a sterile isotonic solution were injected intravenously. The mean values of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and 28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The data show that less calcium is absorbed from foodstuffs as compared to a preparation of optimal bioavailability. But in this study only the difference between absorption from the milk and from the meal was statistically significant. Therefore, it is possible to obtain a sufficient calcium supply of the human body also by properly selected foodstuffs.

Adult↗

Limited effect of refined carbohydrate dietary supplementation on colonization of the gastrointestinal tract of healthy subjects by Candida albicans.

BACKGROUND: Infections due to Candida albicans occur readily in situations in which ample glucose is available. In mice, dietary refined carbohydrate supplementation leads to higher rates of Candida growth in the gastrointestinal tract and favors mucosal invasion. OBJECTIVE: The modulating properties of dietary carbohydrate supplementation on colonization of the human gastrointestinal tract by C. albicans were evaluated. DESIGN: A 2-step study was conducted in 28 healthy volunteers. First, we determined the subjects' habitual uptake of refined carbohydrates and correlated these data with the C. albicans blastoconidia concentration in the mouth washes and feces of subjects with no intervention. Second, we compared C. albicans counts in the specimens before, during, and after a high-sugar diet. RESULTS: No correlation between C. albicans counts in the specimens and the habitual uptake of refined carbohydrates was observed. A high-sugar diet did not increase the frequency of C. albicans-positive samples, the number of subjects positive for C. albicans in the mouth washes, or the concentration of candidal blastoconidia in the samples of the 28 subjects. However, in selected subjects with elevated counts of oral C. albicans, we observed an increase in fecal C. albicans counts in response to the diet. CONCLUSIONS: The effect of adding a high amount of refined carbohydrates to the diet of healthy human subjects has a limited influence on Candida colonization. Follow-up studies should define whether selected patient groups might benefit from dietary restriction of refined carbohydrates.

Adolescent↗

Development and prevalidation of two different ELISA systems for the potency testing of Clostridium perfringens beta and epsilon-toxoid containing veterinary vaccines.

The potency testing of Clostridium perfringens mono- and multicomponent veterinary vaccines is currently performed with the mouse neutralisation test (MNT) to estimate levels of C. perfringens beta- and epsilon-antitoxin levels in the sera of rabbits immunised with the vaccine. Two in vitro methods based on monoclonal antibodies (mAb) have been developed for the determination of specific antibodies against C. perfringens beta-toxin (capture ELISA) and epsilon-toxin (competitive ELISA) in these sera. Both test systems show high specificity and good reproducibility. These ELISA procedures were used in addition to the routine batch potency test in mice (MNT) to determine beta- and epsilon-antitoxin levels in 523 samples of rabbit serum. There was good agreement between the rank order of sera determined in vivo and the rank order determined in vitro. Linear regression analysis gave correlation coefficients of 0.88 for the capture ELISA and 0.41 for the competitive ELISA, with a significance level of P < 0.01 in both cases. Furthermore, a prevalidation study was carried out in four laboratories to evaluate the transferability of the ELISA procedures and the interlaboratory reproducibility of the results. Three coded serum samples were tested several times. The results indicated that both ELISA systems are suitable candidates to replace the MNT used for the potency testing of beta- and epsilon-toxoid in mono- and multicomponent veterinary vaccines. However, these assays still need to be validated in an international collaborative study.

Animals↗

Identification of the Plasmodium chabaudi homologue of merozoite surface proteins 4 and 5 of Plasmodium falciparum.

Previous studies of Plasmodium falciparum have identified a region of chromosome 2 in which are clustered three genes for glycosylphosphatidylinositol (GPI)-anchored merozoite surface proteins, MSP2, MSP5, and MSP4, arranged in tandem. MSP4 and MSP5 both encode proteins 272 residues long that contain hydrophobic signal sequences, GPI attachment signals, and a single epidermal growth factor (EGF)-like domain at their carboxyl termini. Nevertheless, the remainder of their protein coding regions are quite dissimilar. The locations and similar structural features of these genes suggest that they have arisen from a gene duplication event. Here we describe the identification of the syntenic region of the genome in the murine malaria parasite, Plasmodium chabaudi adami DS. Only one open reading frame is present in this region, and it encodes a protein with structural features reminiscent of both MSP4 and MSP5, including a single EGF-like domain. Accordingly, the gene has been designated PcMSP4/5. The homologue of the P. falciparum MSP2 gene could not be found in P. chabaudi; however, the amino terminus of the PcMSP4/5 protein shows similarity to that of MSP2. The PcMSP4/5 gene encodes a protein with an apparent molecular mass of 36 kDa, and this protein is detected in mature stages of the parasite. The protein partitions in the detergent-enriched phase after Triton X-114 fractionation and is localized to the surfaces of trophozoites and developing and free merozoites. The PcMSP4/5 gene is transcribed in both ring and trophozoite stages but appears to be spliced in a stage-specific manner such that the central intron is spliced from the mRNA in the parasitic stage in which the protein is expressed.

Amino Acid Sequence↗

Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change.

Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to alpha5beta1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate-binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B-dependent transcriptional regulation of interleukin-1alpha, which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease. The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion.

Animals↗

[Kallikrein concentration in mixed saliva after contraceptive administration or postmenopausal hormone replacement].

BACKGROUND: The aim of our study was to evaluate the premise (Jenzano 1992) that estrogen influences the female mixed saliva kallikrein level (MSK). METHODS: We estimated the MSK level from woman between the ages of 17 and 39 with (n = 20) and without (20) contraceptive medication (at least an one year treatment) and postmenopausal women between the ages of 47 and 65 with (n = 20) and without (n = 22) hormonal substitution. Kallikrein was estimated by means of the cleavage of the chromogenic tripeptide Val-Leu-Arg-p-nitranilide (SIGMA) and absorbance measuring of p-nitraniline at 405 nm. RESULTS: A Wilcoxon test was conducted for statistical analysis. The MSK level decreases significantly (p = 0.000) under contraceptive medication (estrogen component: synthetic ethinyl-estrogen). However the MSK level of postmenopausal women showed no significant alteration (p = 0.158) after hormone substitution (estrogen component: natural estrogen). The finding may be due to the weaker effect of the estrogen used in post-menopausal hormone therapy. CONCLUSIONS: Our results demonstrate that estrogenic substances affect salivary kallikrein levels.

Adolescent↗

Biokinetic studies in humans with stable isotopes as tracers. Part 1: A methodology for incorporation of trace metals into vegetables.

The metabolism and biokinetics of trace metals in humans can be successfully studied employing stable isotopes of the investigated elements as tracers. For the estimation of the bioavailability and the intestinal absorption from solid food, materials are required which have been intrinsically labelled with the chosen stable tracer, since the use of an extrinsic label may lead to erroneous results. Here a technique for producing intrinsically labelled vegetables is presented and optimized with regard to molybdenum, gadolinium and ruthenium, elements of interest in the field of radiation protection and/or nutrition. These feasibility studies were aimed to determine the most favourable conditions for the production of vegetables containing the selected tracers in amounts high enough to enable successful biokinetic studies in humans. In this optimization study the natural elements were used instead of the more expensive stable isotopes. Mo is readily absorbed both into cress (Lepidium sativum) and into french beans (Phaseolus vulg. var. nanus). Gd uptake into cress is moderate, while Ru may be easily and successfully incorporated only into sprouts of mung beans (Vigna radiata).

Biological Availability↗

Biokinetic studies in humans with stable isotopes as tracers. Part 2: Uptake of molybdenum from aqueous solutions and labelled foodstuffs.

Molybdenum (Mo) has been identified as an essential trace mental for humans. The present study was aimed at the assessment of data on intestinal Mo absorption from aqueous solutions and from foodstuffs in humans applying the methodology for intrinsic labelling described in Part 1. The intestinal absorption of Mo was investigated by means of a double tracer method in 3 healthy volunteers on a total of 15 occasions. When administered as aqueous solution, almost complete uptake of Mo was observed up to doses of 1 mg and only a slight decrease for higher doses. But addition of black tea reduces the absorbed fraction by about a factor of ten. Studying Mo absorption from food, intrinsically labelled cress showed a reduced uptake as compared to extrinsically labelled cress and aqueous solutions. Even less Mo was absorbed from an extrinsically labelled composite meal. The data obtained demonstrate a pattern of intestinal Mo absorption which is different from that of other essential trace metals, e.g., Fe or Co.

Food↗

A revised model of molybdenum biokinetics in humans for application in radiation protection.

The biokinetic models used to describe the fate of radionuclides incorporated by humans often lack the support of reliable experimental evidence. Recent investigations conducted in human volunteers using stable isotopes as tracers have shown that some important features of the biokinetics of ingested molybdenum are not taken into account by the model currently adopted by the International Commission on Radiological Protection. Compartmental analysis has been used to develop an improved model which better describes the available data. Major modifications with respect to the International Commission on Radiological Protection model concern the description of the urinary excretion and the values of the transfer parameters describing intestinal absorption and distribution to organs. Separate sets of parameter values for liquid and solid materials are also given.

Humans↗

Acute effect of metipranolol on the retinal circulation.

AIM: To assess the effect of topical and systemic application of a beta adrenergic receptor blocker on retinal haemodynamics. METHODS: 24 healthy subjects were included in this double masked, randomised, placebo controlled crossover study. Metipranolol, a non-selective beta adrenergic receptor blocking agent was used as test drug. In all subjects arm-retina time, arteriovenous passage time, arterial mean dye velocity, the arterial vessel diameters, and capillary flow velocity were quantified from digital video fluorescein angiograms. RESULTS: A significant effect was observed on the arteriovenous passage time (p < 0.05), the arterial mean dye bolus velocity (p < 0.05), and capillary blood velocity (p < 0.05), but not on the arterial vessel diameter. The arterial mean dye bolus velocity and capillary blood velocity increased after application of the test drug (topical and systemic). In tandem with this a decrease of the arteriovenous passage time was observed. The perfusion pressure increased after topical application and remained unchanged after systemic application of metipranolol. CONCLUSIONS: This study shows that systemic as well as topical application of metipranolol leads to increased retinal blood flow velocities. The implications of these results for treatment with beta adrenergic receptor blockers is not clear. However, in view of these data it is very unlikely that treatment with metipranolol has a negative effect on retinal blood flow.

Administration, Oral↗

Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis.

BACKGROUND: Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. AIMS: To investigate this effect in patients with genetic haemochromatosis, and, more importantly, the effect of regular tea drinking on the accumulation of storage iron in these patients over one year. PATIENTS: Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, they were separated into a group instructed to drink a particularly tannin rich tea regularly with meals and a control group. METHODS: Intestinal iron absorption from a test meal was measured using whole body counting. Body iron stores were evaluated quantitatively by exhaustive phlebotomy, using haemoglobin, saturation of serum iron binding capacity, and serum ferritin for the assessment of body iron status. RESULTS: A significant reduction in iron absorption was observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one third compared with that of the control group. CONCLUSIONS: Regular tea drinking with meals reduces the frequency of phlebotomies required in the management of patients with haemochromatosis.

Adult↗

Reproducibility of technetium-99m-MAG3 clearance using the Bubeck method.

UNLABELLED: The objective of this study was to estimate the reproducibility of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) clearance calculated using a single-sample method. METHODS: One hundred forty-seven patients with urological or ear, nose and throat cancer were analyzed in a retrospective study. Each patient had at least two clearance studies with 99mTc-MAG3 before chemotherapy treatments to monitor renal function. Up to five clearance studies per patient were considered. The reproducibility was estimated by comparing two consecutive investigations. Pairs of investigations with a change in split renal function of more than 5% or an interval of more than 50 days were excluded. Clearance was determined using the Bubeck method. For each pair of consecutive clearance data, the difference between the first and the second measurements was expressed as a percentage of the mean value of the two measurements. The mean of these normalized differences represents the systematic deviation, and the s.d. represents the reproducibility of the compared clearances. RESULTS: After the selection, 242 pairs of consecutive clearance data remained for comparison. Significantly different clearances were observed only between investigations 0 and 1 and between 4 and 5. The systematic deviation of these comparisons totaled -3.8% and -5.7%, respectively. In the other comparisons, no significant deviation induced by the chemotherapy was found. The reproducibility calculated for all comparisons totaled 11.7%. CONCLUSION: The error of reproducibility of 99mTc-MAG3 clearance using the Bubeck method was < or =11.7%. This was an acceptable value, taking into account the greater fluctuation of tubular function compared with the glomerular filtration rate.

Humans↗

Growth and storage of YAC clones in Hogness Freezing Medium.

To date, frozen storage of YAC libraries have relied on the administration of glycerol to the medium subsequent to cell growth. By adding Hogness Freezing Medium prior to inoculation, cultures can be frozen directly after cell growth, with no adverse effect on the stability of the YAC DNA or on the viability of the cells even after repeated freezing and defrosting. Although a relatively simple modification, the procedure notably improves the handling of YAC libraries and significantly reduces the risk of contamination, especially when dealing with large numbers of clones.

Animals↗

Identification of additional rRNA fragments encoded by the Plasmodium falciparum 6 kb element.

Sequences similar to mitochondrial large and small subunit rRNAs are found as small scattered fragments on a tandemly reiterated 6 kb element in the human malaria parasite Plasmodium falciparum. The rDNA sequences previously identified include strongly conserved portions of rRNA, suggesting that fragmented rRNAs derived from them are able to associate into functional ribosomes. However, sequences corresponding to other expected rRNA regions were not found. We here report that 10 of the 13 previously described rDNA regions have abundant small transcripts. An additional 10 transcripts were found from regions not previously known to contain genes. Five of the latter have been identified as rRNA fragments, including those corresponding to the 5'end and 790 loop sequences of small subunit rRNA and the sarcin/ ricin loop of large subunit rRNA. Demonstration that most of the previously described rDNA regions have abundant transcripts and the identification of new transcripts with other portions of conventional rRNAs provide support for the hypothesis that these small transcripts comprise functional rRNAs.

Animals↗

[Quantitative studies of the kallikrein-prokallikrein system in mixed saliva in oral squamous epithelial carcinoma].

Few biochemical analyses on the mixed salivary kallikrein-prokallikrein system exist. At present, there is no statistically relevant information about possible relationships between mixed salivary kallikreins and malignant processes, especially oral squamous cell carcinoma. In order to prove quantitative alterations of the kallikrein-prokallikrein system in the presence of oral squamous cell carcinoma, we estimated the enzyme content in mixed saliva from 15 men with oral squamous cell carcinoma and proenzyme in 14 men with the same tumors. Seventeen males served as controls for enzyme and 16 for proenzyme. Enzymatic cleavage of the chromogenetic tripeptide DL-Val-Leu-Arg-p-nitranilide was used. Additionally, we investigated a control group of 17 women of the same age as the males in order to record normal enzyme and proenzyme levels. The Mann-Whitney-Wilcoxon test showed highly significant elevation of mixed saliva kallikrein (P = 0.0003) and a highly significant increase in prokallikrein (P = 0.0012) in patients with the oral squamous cell carcinomas. The present findings indicate a probable biochemical role of the mixed saliva kallikrein and prokallikrein in the pathogenesis of oral tumors.

Adult↗

A methodology for biokinetic studies using stable isotopes: results of repeated molybdenum investigations on a healthy volunteer.

A method for biokinetic studies in humans using stable isotopes is presented. The technique is based on double tracer administration and on proton activation as the analytical method. As an application, the results of investigations on molybdenum metabolism in humans are reported. The contents of 95Mo and 96Mo in biological samples were determined by inducing (p,n) reactions and by analysing the gamma-rays emitted by the radioactive products. The minimum detectable quantity was 2 ng/mL plasma for both Mo isotopes. Four investigations on molybdenum metabolism were performed on a healthy volunteer subject in the course of 3 yr. Two absorption studies with different amounts of tracers in aqueous solution were performed by giving 96Mo orally and 95Mo intravenously. Two investigations were performed with single oral administration of 96Mo in aqueous solution and of a 96Mo solution mixed with an infant formula respectively. The stability with time of the biokinetic parameters was tested. The fractional absorption values measured in this volunteer were 0.84, 0.98 and 0.95 for three studies with Mo in HCl and 0.51 for a single study with Mo administered in an infant formula, these data are discussed.

Humans↗