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Biomedical subjects

M Götz

Publications and source records attributed to M Götz.

At least 19 recordsLinked to original sources

Health-independent lung transplantation information of parents of children with cystic fibrosis.

BACKGROUND: Twenty-one to 63% of patients with cystic fibrosis (CF) accepted for lung and heart-lung transplantation die on the waiting list. A significant delay between referral and assessment may present an unrecognized hazard toward mortality. METHODS: All parents of children with CF aged 3 to 15 years enrolled in the Vienna CF center were sent questionnaires to investigate their attitudes toward provision of information on lung transplantation (LT). RESULTS: Complete questionnaires were obtained from 59 mothers and 47 fathers of 60 children. Thinking of LT evoked anxiety among 88% of parents, yet 54% wanted to get information at the present time. Parents younger than 30 years and older than 40 years were most interested in obtaining information. Recommendations for the clinicians showed preference for early over health deterioration-induced information (58% vs. 42%). The predominant fears associated with LT were the risk of dying (91%), physical pain (90%), and graft rejection (80%). First information on LT should be presented by the usual CF physician (96%) in the form of a face-to-face conversation (97%) and in the absence of the child (77%). Among the desired content areas, information about the chances LT offers had highest priority (86%). Thorough explanation of the rationale behind the transplant proposal (81%) and details of the whole procedure were requested. If their child were to actually need a transplant, many parents would rely on the doctor's assistance in jointly talking to the child (64%). The most helpful interventions for decision-making included meetings with successfully transplanted individuals (84%) and repeated discussions with experts. CONCLUSIONS: Information may be implemented in medical care as a preventive strategy to avoid dangerous delays in case of unexpected turns toward the need for LT. A policy of recognition and acceptance of parental reluctance is mandatory.

Adolescent

Characterization of components of the murine B cell receptor complex and their role in anti-Ig stimulation.

Signal transduction in B cells is mediated by B cell receptor (BCR) complexes that are composed of membrane immunoglobulins (mIg) and additional proteins (e.g. Ig-alpha and Ig-beta) that have been implicated with several aspects of B cell activation. In this paper, experiments are described that have been designed to characterize new components of the BCR and to elucidate their involvement in B cell activation directly after the binding of anti-Ig. The data obtained prove the assumption that IgM is degraded after internalization. Neither immunoglobulin nor the Ig-alpha/beta heterodimer are re-expressed after they have disappeared from the cell surface. The newly detected Ig-alpha associated proteins are neither degradation products of immunoglobulins nor different forms of Ig-alpha or Ig-beta. In addition, they are not recognized by antibodies against any of the kinases known to date. The mIg molecules are linked to the cytoskeleton and internalized. On the other hand, the additional Ig-alpha associated proteins as well as the Ig-alpha/beta heterodimer could not be detected in the detergent-insoluble fraction. The former molecules remain on the B cell surface where they are attached to the unaffected isotype and might interact with downstream members of the signalling cascade. In addition, evidence is presented that the internalization of the receptor complex is not necessary for signal transduction and B cell activation. From these results the authors conclude that the BCR complexes are removed from the cell surface after binding of ligands, probably to prevent further activation of this cell, while the Ig-alpha associated proteins interact with the intracellular components of the signal transduction pathway to promote the further activation of the B cells.

Animals

Tenascin-C synthesis and influence on axonal growth during rat cortical development.

Several putative guidance molecules are restricted to the marginal and subplate zones, the major fibre tracts in the developing cortex. It is presently unknown how their distribution is achieved and how these molecules affect neurite extension. Tenascin-C is of particular interest in this context, because it may either promote or deflect growing axons depending on its mode of presentation. Therefore, the cellular origin of tenascin-C in the developing rat cortex and its effects on the extension of cortical afferents and efferents were examined. Tenascin-C protein is first restricted to the marginal and subplate zones and spreads later into the developing grey matter, in close correlation with afferent innervation. In situ hybridization showed that tenascin-C mRNA is first confined to the ventricular zone, at some distance from the location of the protein, while at later stages tenascin-C-synthesizing cells become scattered throughout the cortical thickness, concomitant with the spread of the protein. In order to assess its function, monoclonal antibodies directed against different domains of tenascin-C were used in a quantitative axonal outgrowth assay. These perturbation experiments suggested that distinct tenascin-C fibronectin type III repeats sustain the growth of thalamic and cortical axons on cortical membrane carpets, whereas the EGF-type repeats are not involved. The combination of different antibodies revealed that separate fibronectin-type III repeats exert cooperative effects. These results suggest that ventricular zone cells regulate the establishment of thalamic and cortical axonal projections through locally restricted deposition of tenascin-C.

Animals

Diagnosis of trichothiodystrophy in 2 siblings.

Trichothiodystrophy (TTD) is a rare autosomal recessively inherited disorder which is characterized by sparse and brittle hair with low cystine content. It is often associated with physical and mental retardation. We report 2 cases of TTD in 2 sibs who were born to related parents. The children showed clinical features typical of TTD and in addition other symptoms such as epilepsy, ataxia, spasticity, strabismus, atopic dermatitis, dysarthria and hyperextensible fingerjoints. The sulfur content of hair was reduced to about 50% of normal values and scanning electron microscopy of hair showed trichorrhexis nodosa, trichoschisis, missing cuticle scales with weathering of hair shafts. Under polarizing microscopy an alternating dark and bright banding was found. The present cases show that the correct diagnosis of TTD in practice can be impeded for many years because of the heterogeneous clinical appearance and that the determination of the sulfur content in hair is a simple but indispensable method.

Ataxia

Sensitization to Aspergillus fumigatus and lung function in children with cystic fibrosis.

Colonization with Aspergillus fumigatus (Af) constitutes a common finding in children with cystic fibrosis (CF). The relationship between sensitization to Af and lung functon (LF) was studied in 118 patients with CF (61 girls and 57 boys; mean age: 14.3 yr; SD: 7 yr). Mean follow up was 2.2 yr. On average, 8.1 (SD: 4.8) LF tests were performed per patient. Measurement of total IgE and specific IgE antibodies to Af, and a skin prick test (SPT) for Af, were done once a year. Thirty-one children (26%) were sensitized to Af. On average, LF parameters were not significantly different in Af-sensitized children than in nonsensitized children. Linear regression analyses were performed, using the repeated measures design. With adjustment for gender, age, height, and weight, sensitization to Af was associated with lower values of FEV1 (beta = -0.209; p < 0.05) and FEF(25-75) (beta = -0.356; p < 0.01). Analysis of different subgroups of sensitization demonstrated the effect on LF only in Af-sensitized patients with elevated total IgE levels, and not in Af-sensitized patients with normal IgE levels. Furthermore, there was evidence for a more rapid decline in LF for Af-sensitized patients with elevated total IgE levels than in those with normal IgE levels. We conclude that sensitization to Af in the presence of increased IgE values is associated with lower LF values in children with CF.

Adolescent

Oilseed rape pollen is a potentially relevant allergen.

Oilseed rape (Brassica napus) (OSR) is a partly wind-pollinated crop which has been increasingly cultivated both in Europe and overseas. Allergological data about OSR is scarce and controversial. We evaluated the frequency of sensitization to OSR pollen by skin prick test and RAST over a period of 1 yr. Airborne OSR pollen load and the agricultural role of this crop were analysed. Furthermore, six patients were investigated by immunoblot. In 4468 patients with suspect inhalant allergy investigated between June 1994 and May 1995, routine skin prick testing revealed OSR sensitivity in 7.1% of pollen-allergic patients. In all, monovalent sensitization was detected in nine patients. Routine pollen counts showed daily maxima not exceeding 50 grains/m3/24 h, but airborne OSR pollen has continuously increased during the last decade correlating with the increasing acreage. Characterization of OSR allergens by immunoblot revealed major allergens of 6/8 kD, 12/14 kD and in the high molecular weight range at 33, 42, 51, 58/61 and 70 kD. Some OSR proteins may cross-react with birch pollen allergens. In summary, the results suggest that OSR pollen is a moderate but true source of allergy and may sensitize despite low pollen exposure.

Allergens

Dual action of a carbohydrate epitope on afferent and efferent axons in cortical development.

During development of the mammalian cerebral cortex, ingrowing afferents from the thalamus take a path that is different from that of axons leaving the cortical plate. Thalamic axons arrive at the cortex at the time before their target cells of layer 4 are generated in the ventricular zone, but they invade the cortex only shortly before these cells have migrated to their final position in the cortex. Growth-promoting molecules are up-regulated in the developing cortical plate during this period. To identify such molecules, we have generated monoclonal antibodies against membrane preparations from rat postnatal cortex. In Western blots, one antibody (mAb 10) recognized a carbohydrate epitope of a glycoprotein with an apparent molecular weight extending from 180 to 370 kDa. Immunohistochemical staining revealed that the staining pattern of mAb 10 at embryonic stages delineates the pathway of thalamocortical axons, with only very faint labeling of the corticofugal pathway. In vitro assays in combination with time-lapse imaging indicated that mAb 10 has opposite effects on the growth of thalamic and cortical axons. The growth speed and axonal elongation of thalamic fibers on postnatal cortical membranes preincubated with mAb 10 was reduced compared with untreated cortical membranes. In contrast, cortical axons grew faster and stopped their growth less frequently after addition of mAb 10 to a cortical membrane substrate. Taken together, these results suggest that a carbohydrate moiety of a membrane-associated glycoprotein plays a role in the segregation of afferent and efferent cortical axons in the white matter. Moreover, the epitope recognized by mAb 10 might also contribute to regulation of the timing of the thalamocortical innervation at later developmental stages.

Aging

Neurotransmitters in CSF of idiopathic adult-onset dystonia: reduced 5-HIAA levels as evidence of impaired serotonergic metabolism.

While several radiological findings point towards the basal ganglia as a possible anatomical site of the lesion in dystonia patients the biochemical basis of the disorder is still unknown. 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels-the respective metabolites of serotonin and dopamine-were measured in lumbar cerebrospinal fluid (lCSF) of 15 patients with idiopathic adult-onset focal dystonia and in lCSF of 11 controls. 100 microliters lCSF were analyzed for 5-HIAA and HVA by reversed-phase HPLC with electrochemical detection. 5-HIAA levels were significantly reduced in dystonia patients (11.4 micrograms/ml) compared to controls (18.4 ng/ml) (p < 0.02). HVA levels in dystonia patients (30.3 ng/ml) were below control values (41.6 ng/ml) but this finding did not reach statistical significance. Decreased lCSF levels of 5-HIAA suggest an impaired serotonin metabolism in patients with idiopathic adult-onset dystonia. This observation may provide a biochemical basis for a more specific pharmacotherapy in dystonia patients.

Adult

Ultrasound velocity of the tibia in normal German women and hip fracture patients.

One of the latest developments in quantitative ultrasound (QUS) is the measurement of the speed of sound (SOS) of cortical bone of the midtibia. To determine the diagnostic validity of this method we measured 150 healthy women aged 22-94 years. Additionally, we report on first results of patients with hip fracture. Precision in vivo of the tibial QUS expressed as the percentage coefficient of variation (CV) was 0.39% for the first day and 0.45% after repositioning the second day (mean CV = 0.42%). No significant dependency of tibial SOS was found with weight, height, and body mass index in pre- and postmenopausal women. There was a significant decline of SOS with age in postmenopausal women (SOS = 4225 - 5.3 age, r = -0.46, P < 0. 001), whereas premenopausal women showed no decline (SOS = 3906 + 1. 3 age, r = 0.13, ns) Mean SOS values of premenopausal women were significantly higher than those of postmenopausal women (3960 +/- 78.7 m/second and 3898 +/- 120 m/second, respectively, P < 0.001). Postmenopausal women on estrogen substitution had significantly higher mean tibial SOS values than age-comparable postmenopausal women without estrogen substitution (3980 +/- 99 m/second and 3869 +/- 100 m/second, respectively, P < 0.001). Significant difference between age-matched healthy women, n = 11, and hip fracture patients, n = 13, expressed as z-score of -1.4 SD was found. In conclusion, tibial QUS declines with age and detects higher values in premenopausal women and postmenopausal women on estrogen substitution and lower values in hip fracture patients. Further prospective studies are needed to clarify its role in fracture risk assessment.

Adult

Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington's disease.

The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum--globulus pallidus--thalamus--striatum. Striatal neurone degeneration is a hallmark in Huntington's disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-microns-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington's disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri's principle and the optical disector. Mean neurone number in the controls was 646,952 +/- 129,668 cells versus 291,763 +/- 60,122 in Huntington's disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 +/- 3,028,944 versus 6,961,989 +/- 2,241,543 in Huntington's disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas' impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington's disease patients = 24.4 +/- 8.1; controls = 15.0 +/- 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington's disease.

Adult

Acute MPTP treatment produces no changes in mitochondrial complex activities and indices of oxidative damage in the common marmoset ex vivo one week after exposure to the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause a Parkinsonian syndrome in man and non-human primates. Hypotheses concerning the pathogenetic mechanisms of MPTP toxicity on nigro-striatal dopaminergic neurons relate to impairment of mitochondrial function and oxidative stress. However, surprisingly few primate studies addressed these issues ex vivo. Thus, the present study assessed the enzyme activities of the respiratory chain, GSH/GSSG and ubiquinol/ubiquinone content in the MPTP primate model (common marmoset, Callithrix jacchus; 2 mg MPTP-hydrochloride/kg body wt were injected subcutaneously (s.c.) on four consecutive days; animals were sacrificed 7 days after last MPTP exposure). Activities of respiratory chain enzymes were measured in crude homogenates of the caudate nucleus, because the probable toxic metabolite of MPTP, MPP+, is transported into dopaminergic neurons via the dopamine uptake system in striatal synapses and mitochondria are concentrated in axonal terminals. Since MPP+ can damage membranes of axonal terminals of nigro-striatal neurons we measured GSH/GSSG contents in the putamen and ubiquinol/ubiquinone concentrations in the substantia nigra and putamen as indices of oxidative damage. At the time of sacrifice MPTP-induced deficits comprised severe behavioural Parkinsonian symptoms, profound depletion of striatal dopamine and its major metabolites as well as pronounced loss of nigro-striatal neurons. Despite these severe lesions, acute MPTP treatment had no effect on any of the enzymes of the respiratory chain in the caudate nucleus and indices of oxidative damage in both the substantia nigra and putamen. These results suggest that factors other than mitochondrial impairment and/or oxidative stress may be involved in MPTP neurotoxicity in primates. Alternatively, early compensatory mechanisms and/or transient effects could account for the reported results and will be discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Allergic contact dermatitis to artificial fingernails prepared from UV light-cured acrylates.

BACKGROUND: Contact dermatitis from artificial nails made from self-curing acrylic resins is occasionally reported. Recently, UV light-cured products introducing new acrylics have become available. OBJECTIVE: Our purpose was to identify relevant allergens in commercial light-curing products by patch tests and to evaluate the efficacy of "hypoallergenic" products by inclusion into the test series. METHODS: Patients wearing photobonded acrylic nails who had perionychial and subonychial eczema were patch tested with an acrylate battery and "hypoallergenic" commercial products. RESULTS: Triethyleneglycol dimethacrylate, hydroxyfunctional methacrylates, and (meth)-acrylated urethanes proved to be relevant allergens in photobonded nail preparations. Methacrylated epoxy resin sensitization was not observed. All "hypoallergenic" products provoked positive reactions. CONCLUSION: The omission of irritant methacrylic acid in UV-curable products does not reduce the high sensitizing potential of new acrylates. In contrast to the manufacturers' declarations, all "hypoallergenic" products continue to include acrylate functional monomers and therefore continue to cause allergic sensitization.

Acrylates

Formaldehyde and phenol exposure during an anatomy dissection course: a possible source of IgE-mediated sensitization?

The sensitizing potency of formaldehyde and phenol exposure during 4 weeks of an anatomy dissection course was assessed in 45 medical students. Specific IgE against formaldehyde by RAST and by ELISA and specific IgE against phenol by ELISA were assessed before and after the course. At the start of the course, symptoms, type I allergy, respiratory diseases, and smoking habits were noted. At the end of the course, only symptoms experienced during the dissection lessons were assessed. Indoor formaldehyde levels were measured continuously. The mean indoor formaldehyde level was 0.124 +/- 0.05 ppm, with a minimum of 0.059 ppm and a maximum of 0.219 ppm. Specific IgE against formaldehyde or phenol was found in none of the subjects at the beginning of the course, and no student showed specific IgE against formaldehyde or phenol after the course. Assessment of primarily irritant symptoms during the lesson revealed itch and paraesthesia of hands in 33/45 students (P < 0.00005), headache in 15/45 students, burning eyes in 13/45 students (P < 0.02), dizziness in 8/45 students (P < 0.008), sneezing in 4/45 students, epistaxis in 2/45 students, and shortness of breath in 1/45 students. According to our data, 1-month exposure to formaldehyde and phenol during an anatomy dissection course does not induce specific IgE against formaldehyde or phenol.

Adolescent

Patch test reactions in children, adults and the elderly. A comparative study in patients with suspected allergic contact dermatitis.

The age- and sex-related distribution of positive patch test reactions was investigated in 234 children (0-7 years, n = 72 and 8-14 years, n = 162), 1200 adults (20 to 50 years) and 295 elderly patients (> or = 70 years) with suspected allergic contact dermatitis using a European standard series. In girls from 0 to 7 years, the most frequent contact allergens were thimerosal (37.5%) and nickel (27.5%), in girls from 8 to 14 years, nickel (28.7%) and thimerosal (26.6%), in women, thimerosal (25.3%) and nickel (25.2%), and in elderly women, nickel (12.6%) and balsam of Peru (9.7%). The most frequent contact allergens in boys from 0 to 7 years were ethylmercuric chloride (28.1%) and thimerosal (25.0%), in boys from 8 to 14 years, thimerosal (30.9%) and ethylmercuric chloride (14.7%), in men, thimerosal (21.1%) and ethylmercuric chloride (13.7%) and in elderly men, nickel (11.2%) and balsam of Peru (6.7%). Females showed more positive reactions than males. Whilst 0 to 7 year-old girls and boys showed relatively more frequent reactions, the elderly of both sexes were clearly less affected. Nickel is the most frequent contact allergen in females of 8 years and more. In men, thimerosal is most frequent and reactions to balsam of Peru show a peak incidence in the elderly. Results indicate that patch testing should be considered in children and elderly patients with appropriate indications.

Adolescent