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Biomedical subjects

I Werner

Publications and source records attributed to I Werner.

At least 19 recordsLinked to original sources

Evaluation of inspiratory muscle function in a healthy austrian population--practical aspects.

BACKGROUND: There is no clear evidence whether inspiratory muscle strength (Pi(max)) is closely linked to inspiratory muscle endurance (T(lim)). Moreover, normal values of T(lim), measured by flow-resistive loads, have not been established. OBJECTIVES: We tried to find answers to the following questions: Is it possible to establish normative values of T(lim) when using flow-dependent, resistive loads? Are Pi(max) and Borg scale values predictors of T(lim)? Are anthropometric and spirometric data closely related to T(lim)? Is it really necessary to measure T(lim) in addition to Pi(max) when evaluating inspiratory muscle function? METHODS: Sixty-eight healthy Austrian volunteers between 17 and 75 years of age and with a sedentary lifestyle participated in our study. Pi(max) was defined as the maximal inspiratory mouth pressure, measured with a differential pressure transducer. T(lim) was determined as the time span until exhaustion, while breathing against a resistive loading device. RESULTS: Pi(max) values showed a low intra- and high interindividual variability for both sexes and were significantly age, weight and height dependent. For male subjects, Pi(max) was also significantly related to spirometric parameters. T(lim) values showed a very high interindividual variability, but a low intraindividual variability. Interestingly, no correlation was found between T(lim) and Pi(max), nor lung function parameters and age. CONCLUSIONS: The results indicate that both Pi(max) and T(lim) have to be determined when inspiratory muscle function is measured. Normal values for T(lim), evaluated by flow-resistive loads, cannot be satisfactorily established due to the high interindividual variability.

Adolescent↗

Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis?

OBJECTIVE: In 2003 we identified a family with familial hypocalciuric hypercalcemia (FHH) (heterozygous CASR gene mutation L173P) and a mutation in the pancreatic secretory trypsin inhibitor gene (SPINK1) (N34S). While family members with an isolated calcium-sensing receptor gene (CASR) mutation remained healthy, a combination of the CASR and SPINK1 gene mutation caused chronic pancreatitis (CP). We thus speculate that the combination of two genetic defects affecting calcium homeostasis and pancreatic enzyme activation might represent a novel approach in chronic inherited pancreatic disease. We therefore sought to explore whether CASR gene mutations were prevalent in a cohort of patients with CP and confirmed SPINK1 mutations. MATERIAL AND METHODS: A cohort of 19 families (n=170) with a history of idiopathic CP (ICP) was screened for mutations within the CASR gene; 104 members of that cohort had a mutation (N34S) within the SPINK1 gene and 66 of those were suffering from CP. The entire CASR gene was screened for single strand conformation polymorphism under varying polyacrylamide gel conditions and subjected to direct dideoxy nucleotide sequencing of amplified cDNA. RESULTS: Single-strand conformation polymorphisms were observed in 59 samples, clustering of exons 3, 4 and 7. DNA sequence analysis revealed a yet unreported missense mutation in exon 7 (R896H) and two conservative mutations in exon 4 (F391F) and exon 7 (E790E). Furthermore, an intronic polymorphism in nucleotide position 493-19 G>A was detected in 19 out of 170 members of that cohort. CONCLUSIONS: We identified three novel calcium-sensing receptor gene mutations (1 missense mutation, 2 silent mutations and 1 intronic polymorphism) in a cohort of 19 families with ICP. In particular, the kindred with the R896H mutation presenting with a similar pedigree to the family described above may indicate a role for CASR gene mutations in SPINK1-related CP. Again, only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. We suggest that the CASR gene is a novel yet undetected co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.

Calcium Signaling↗

MTHFR 677TT genotype increases the risk for cervical artery dissections.

The methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was studied in 174 German patients with cervical artery dissection (CAD). The results were compared with published data on 927 healthy German controls. In the series of patients, the frequency of T alleles and of TT carriers was slightly higher (13.8%) than among the healthy controls (10.6%). In patients with multiple dissections (n = 50), the proportion of TT carriers (18%) was found to be even higher and correlated with the number of events. The MTHFR C677T polymorphism was suggested to modify the risk for CAD.

Aortic Dissection↗

Geochemistry and bioavailability of metals in sediments from northern San Francisco Bay.

In this study, metals (Be, Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd, Pb and Hg) in the fine-grained fraction (<63 microm) from 12 sites at different locations in northern San Francisco Bay over a year period from March 2000 to March 2001 were analyzed after acid extraction. The results showed that metal concentrations in the sediments varied from site to site, whereas some of them were found elevated with respect to the sediment of Tomales Bay, CA, which has little contamination history, indicating an enrichment of the metals in the sediment samples analyzed. Sediment toxicity and bioaccumulation evaluation by a clam species, Macoma nasuta, exposed to the sediment samples collected from the six sampling sites was carried out. The results showed that the sediment samples tested significantly reduced clam survival. Toxicity of the sediments to the clam was, in part, related to elevated metal concentrations in the sediments. In order to examine geochemistry of the metals and to understand potential correlations between metal concentrations and geochemical matrix elements of the sediments, bioavailability and toxicity of the metals, detailed analysis of metal concentrations associated with total organic carbon and the Fe-oxy-hydroxides in the sediment samples was performed. The analysis showed that sediment geochemistry appeared to influence metal bioavailability and may have important impacts on the toxicity of these metals to the clam.

Animals↗

Alpha-1-antitrypsin deficiency alleles are not associated with cervical artery dissections.

The authors searched for the presence of alpha-1-antitrypsin (AAT) deficiency alleles PiZ and PiS in 74 patients with spontaneous cervical artery dissections (sCADs) and in 74 healthy control subjects. In both groups, the authors found four carriers of deficiency alleles. The connective tissue morphology of one additional patient with sCAD with PiZM genotype and her relatives was studied in skin biopsies. The PiZ allele did not segregate with morphologic alterations of the dermal connective tissue in the family. Therefore, AAT deficiency alleles may not play a role in the etiology of sCAD.

Adult↗

TLC and HPLC characteristics of desacetylmatricarin, leucodin, achillin and their 8alpha-angeloxy-derivatives.

Five guaianolides, including two pairs of isomers, from a Hungarian taxon of the Achillea millefolium group were characterized analytically. Different chromatographic systems on TLC and HPLC were developed for the analysis of these compounds. TLC of leucodin, 8alpha-angeloxy-leucodin, achillin, 8alpha-angeloxy-achillin and desacetylmatricarin was performed on silica gel using dichloromethaneacetone and cyclohexane-ethylacetate mixtures as mobile phases. HPLC on stationary phases as LiChrospher RP2, LiChrospher RP8, LiChrospher RP18e, Hypersil BDS C18 and Aquasil C18 required isocratic and gradient systems with different methanol-water mixtures as mobile phases. The presented RF values and retention times allow the identification of the respective 2-oxo-guaianolides which are marker substances for certain non-proazulene containing species. Their TLC and HPLC fingerprints are compared to those of proazulene containing species and are relevant for quality control.

Achillea↗

Combination of chromatographic and spectroscopic methods for the isolation and characterization of polar guaianolides from Achillea asiatica.

Four polar guaianolides, 8alpha-angeloxy-2alpha,4alpha, 10beta-trihydroxy-6betaH,7alphaH, 11betaH-1(5)-guaien- 12,6alpha-olide; 8alpha-angeloxy-1beta,2beta:4beta,5beta-diepoxy- 10beta-hydroxy-6betaH,7alphaH,11betaH-12,6alpha-guaianolide; 8alpha-angeloxy-4alpha, 10beta-dihydroxy-2-oxo-6betaH, 7alphaH, 11betaH- 1(5)-guaien- 12,6alpha-olide and 8-desacetyl-matricarin, were isolated from Achillea asiatica and characterized by TLC, MS, IR, HPLC and diode array detection. Purified extracts were separated by means of flash chromatography. HPLC separations were achieved using different methanol-water gradients as mobile phase and LiChrospher 100-RP8 5 microm or Zorbax SB-C8 3.5 microm as stationary phases. The chromatographical data are compared to those of the proazulene 8alpha-tigloxy-artabsin which shows antiinflammatory effects. By means of these characteristics the identification of the guaianolides with potential antiphlogistic properties is also possible from other sources.

Asteraceae↗

Pathogenesis of cervical artery dissections: association with connective tissue abnormalities.

BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. OBJECTIVE: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. METHODS: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers-Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. CONCLUSION: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Adult↗

[Prevalence of sleep disorders in school children between 11 and 15 years of age].

UNLABELLED: Little is known about sleep disorders in children and adolescents that might affect physical and emotional well-being. Depending on age and size of the cohort group, and differences in questionnaires, prevalence varies between 1-43% in international studies. We examined the prevalence of symptoms characteristic of sleep disorders in school aged children with a questionnaire which allows indication of symptoms by the children themselves. METHODS: An anonymous questionnaire, based on the German Dresden questionnaire, with 22 questions concerning the main symptoms of obstructive sleep apnea syndrome (OSAS), general symptoms of para- and insomnia as well as sociodemographic data, was developed. 332 pupils (age: 11-15 y, mean: 12.75 y; median: 12 y; 56% female, 44% male) in 2 high schools in Vienna were investigated. RESULTS: 28% (n = 93/332) of the examined group reported snoring (the main symptom of OSAS) and/or insomnia (night waking almost every night) or parasomnia (nightmares, night terrors or sleepwalking almost every night). 15% (n = 14/93) of this subgroup reported snoring and para- or insomnia coincidentally. Girls were affected more frequently than boys by nocturnal awakening (79% vs. 56%, p < 0.001) and nightmares (64% vs. 52%, p < 0.01). The snoring group (21% (71/332) of all examined children) was affected more frequently by mouth dryness (16% vs. 4%, p < 0.001), pallor (7% vs. 3%, p < 0.01), night sweats (6% vs. 1%, p < 0.05) and from the following sleep disorders: nightmares (10% vs. 2%, p < 0.01), night terrors (4% vs. 1.5%, p < 0.001), sleepwalking (1.4% vs. 1%, p < 0.05) and nocturnal awakening (16% vs. 5%, p < 0.01). DISCUSSION: Almost every fifth child reports about at least one main symptom characteristic of OSAS. The statistically significant relation between symptoms of OSAS and non-organic sleep disorders shows the necessity of interdisciplinary focusing on sleep disorders. Further epidemiological studies need to be carried out in order to clarify the role of sleep anamnesis in the diagnosis and management of sleep disorders during childhood.

Adolescent↗

Tracer studies with 13C-labeled carbohydrates in cultured plant cells. Retrobiosynthetic analysis of chelidonic acid biosynthesis.

The biosynthesis of chelidonic acid was studied in cell suspension cultures of Leucojum aestivum. Cell cultures were supplied with [U-13C]glucose, [l-13C]glucose or [U-13Cs]ribose/ribulose in standard medium containing unlabeled glucose. 13C labeling patterns of amino acids obtained by hydrolysis of biomass were determined by NMR spectroscopy and compared to the labeling pattern of chelidonic acid. The data document the incorporation of a contiguous 4-carbon fragment derived from the pentose phosphate pool into chelidonic acid. This suggests a biosynthetic pathway involving the condensation of phosphoenolpyruvate with a pentose phosphate followed by dehydration, dehydrogenation, ring closure and decarboxylation conducive to the loss of C-5 of the pentose precursor.

Carbohydrate Metabolism↗

Highly hydroxylated guaianolides of Achillea asiatica and Middle European Achillea species.

From flower heads of Achillea asiatica (L.) Serg., three new guaianolides were isolated by repeated column chromatography and HPLC. The constitution and the stereochemistry of these new, labile compounds were determined by MS, one ((1)H, (13)C, selective (1)H-TOCSY and (1)H-NOESY) and two-dimensional NMR experiments ((1)H, (1)H-COSY, (1)H, (13)C-HSQC, (1)H, (13)C-HMBC). The substances were identified as 8 alpha-angeloxy-2 alpha, 4 alpha,10 beta-trihydroxy-6 beta H,7 alpha H, 11 beta H-1(5)-guaien-12,6 alpha-olide (1), 8 alpha-angeloxy-1 beta,2 beta:4 beta,5 beta-diepoxy-10 beta-hydroxy-6 beta H, 7 alpha H, 11 beta H-12,6 alpha-guaianolide (2) and 8 alpha-angeloxy-4 alpha,10 beta-dihydroxy-2-oxo-6 beta H,7 alpha H, 11 beta H-1(5)-guaien-12,6 alpha-olide (3). They were also detected in Middle European species (Achillea collina, Achillea ceretanica (2x and 4x), Achillea roseoalba, Achillea asplenifolia) by HPLC, TLC and off line MS and have not been described before. The possibility that these compounds might be products of an oxidation process is discussed.

Asteraceae↗

Toxicity of methyl-tert-butyl ether to freshwater organisms.

Increased input of the fuel oxygenate methyl-tert-butyl ether (MTBE) into aquatic systems has led to concerns about its effect(s) on aquatic life. As part of a study conducted by University of California scientists for the State of California, the Aquatic Toxicology Laboratory, UC Davis, reviewed existing literature on toxicity of MTBE to freshwater organisms, and new information was generated on chronic, developmental toxicity in fish, and potential toxicity of MTBE to California resident species. Depending on time of exposure and endpoint measured, MTBE is toxic to various aquatic organisms at concentrations of 57-> 1000 mg/l (invertebrates), and 388-2600 mg/l (vertebrates). Developmental effects in medaka (Oryzias latipes) were not observed at concentrations up to 480 mg/l, and all fish hatched and performed feeding and swimming in a normal manner. Bacterial assays proved most sensitive with toxicity to Salmonella typhimurium measured at 7.4 mg/l within 48 h. In microalgae, decreased growth was observed at 2400 and 4800 mg/l within 5 days. MTBE does not appear to bioaccumulate in fish and is rapidly excreted or metabolized. Collectively, the available data suggests that at environmental MTBE exposure levels found in surface waters (< 0.1 mg/l) this compound is likely not acutely toxic to aquatic life. However, more information is needed on chronic and sublethal effects before we can eliminate the possibility of risk to aquatic communities at currently detected concentrations.

Amphibians↗

Mutations in the tropoelastin gene (ELN) were not found in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The majority of patients with spontaneous cerebral artery dissection show ultrastructural alterations in dermal collagen and elastic fibers. METHODS: We studied the gene encoding tropoelastin (ELN) by reverse transcription-polymerase chain reaction and subsequent sequence analysis in 10 patients with abnormalities in their elastic fibers. RESULTS: No mutations were found in the whole coding region of the ELN gene. The simultaneous visualization and quantification of ELN splice variants by gene scanning enabled the analysis of the regulation of alternative splicing of ELN mRNA. No differences could be detected between fibroblast cultures of the patients and a control subject. CONCLUSIONS: Neither mutations in the ELN gene nor dysregulation of its activity appears to be the cause of the connective tissue disorder that is found in most patients with spontaneous dissections.

Adult↗

Ectoparasite infestation and sex-biased local recruitment of hosts.

Dispersal patterns of organisms are a fundamental aspect of their ecology, modifying the genetic and social structure of local populations. Parasites reduce the reproductive success and survival of hosts and thereby exert selection pressure on host life-history traits, possibly affecting host dispersal. Here we test experimentally whether infestation by hen fleas, Ceratophyllus gallinae, affects sex-related recruitment of great tit, Parus major, fledglings. Using sex-specific DNA markers, we show that flea infestation led to a higher proportion of male fledglings recruiting in the local population in one year. In infested broods, the proportion of male recruits increased with brood size over a three year period, whereas the proportion of male recruits from uninfested broods decreased with brood size. Natal dispersal distances of recruits from infested nests were shorter than those from uninfested nests. To our knowledge, this study provides the first evidence for parasite-mediated host natal dispersal and local recruitment in relation to sex. Current theory needs to consider parasites as potentially important factors shaping life-history traits associated with host dispersal.

Animals↗

Begging signals and biparental care: nestling choice between parental feeding locations

The evolutionary conflict over the amount of resources transferred between a parent and its offspring may be resolved by honest signalling of 'need' by offspring and parental investment in relation to signalling level. In birds, biparental care is the norm and evidence that male and female parents differ in their investment pattern in individual offspring is growing. In an experiment on great tits, Parus major, we investigated how and why parents differ in food allocation when responding to similar chick signals, which supposedly uniquely reflect the chick's nutritional condition. Nestling hunger level was manipulated by food deprivation and hand-feeding. Subsequent filming revealed that parents fed from significantly different locations on the nest and thereby forced chicks to choose between them when competing for favourable positions. Deprived nestlings approached, and fed ones retreated (or were displaced by siblings) from, positions near the female. No such behaviour was observed towards the male. Females allocated more feeds than males to the food-deprived nestlings. The results are discussed in terms of nestling competition for access to 'begging patches'. By varying their 'begging patch' value, parents may exploit competitive inter-sibling dynamics to influence the outcome of competition among chick phenotypes (e.g. 'need', size, sex). Parent birds may thereby exert considerable control over the information content of chick begging behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗