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Biomedical subjects

M Götz

Publications and source records attributed to M Götz.

At least 19 recordsLinked to original sources
PubMed2000

PC3 overexpression affects the pattern of cell division of rat cortical precursors.

The PC3 gene is transiently expressed during neurogenesis in precursor cells of the telencephalic ventricular/subventricular zone, and is rapidly downregulated before cell migration and differentiation. It is thought to have a role in controlling cell proliferation, but its precise function is not known. Here we present evidence that PC3, when overexpressed in vitro by retroviral-mediated gene transfer, acts by interfering with the normal pattern of cell division. Firstly, we report evidence that PC3 overexpression reduces the rate of cell proliferation in both NIH 3T3 cells and embryonic precursor cells from the rat cerebral cortex. Secondly, when studying the pattern of BrdU dilution in clones of cortical precursors, we observe that clones transduced with PC3 show an asymmetric pattern of BrdU dilution more frequently than clones transduced with a control vector. We discuss the hypothesis that the higher number of PC3 transduced clones showing an asymmetric pattern of BrdU dilution may be due to an increase in asymmetric cell divisions.

3T3 Cells↗
PubMed1999

Nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease.

We estimated the total neurone number, glial number, and glial index (ratio glial cells/neurone) in the thalamic mediodorsal nucleus (MD) in seven patients suffering from Huntington's disease (HD; four males, three females, mean age 52.4 +/- 13.6 years) and age- and sex-matched controls (four males, three females, mean age 53.6 +/- 12.1 years) by means of a stereological protocol. The mean total neurone number (N(T)) in the MD of controls was 2,985,188 +/- 174,710, the mean glial number (G(T); astrocytes, oligodendrocytes) 21,785,008 +/- 2,986,678, and the glial index 7.29 +/- 0.88. In HD, the average neurone number was decreased by 23.8% to 2,275,321 +/- 247,162 (Mann-Whitney U-test P < 0.05), the mean glial number by 29.7% to 15,318,895 +/- 1,722,524 (Mann-Whitney U-test P < 0.05), the glial index was slightly reduced to 6.81 +/- 1.06. Gallyas' impregnation for the demonstration of fibrous astroglia gave strongly positive results in all cases with HD and negative results in the controls. The morpho-functional correlation of the results is complicated because individual variability, presence of segregated and parallel neuronal circuits, and plasticity of the adult human CNS must be considered.

Adult↗
PubMed1999

Cystic fibrosis: CT assessment of lung involvement in children and adults.

PURPOSE: To compare a computed tomographic (CT)-based scoring system with nonimaging indexes of pulmonary status in patients with cystic fibrosis. MATERIALS AND METHODS: Pulmonary CT findings were assessed in 117 patients with cystic fibrosis, with cases classified according to three groups by age; 0-5 years, 6-16 years, and 17 years and older. Images were examined for specific abnormalities, and the severity and anatomic extent of each sign were used to generate a score. Scores in each category and the global score for each patient were correlated with pulmonary function test results, clinical status, serum immunoglobulin levels, and genotype, all obtained within 2 weeks of CT. RESULTS: The most frequent individual CT abnormalities were bronchiectasis in 94 (80.3%), peribronchial wall thickening in 89 (76.1%), mosaic perfusion in 71 (63.9%), and mucous plugging in 56 (51.3%) patients. The percentage of patients with specific CT findings and the overall CT scores increased significantly (P < .05) with progressively increasing age groups. All CT findings and the overall CT scores correlated significantly (P < .05) with the pulmonary function test results, serum immunoglobulin levels, and clinical scores. No relationship was observed between genotype and CT scores. CONCLUSION: Scoring of CT studies in patients with cystic fibrosis seems to offer a reliable way to monitor disease status and progression and may provide a reasonable tool to assess treatment interventions.

Adolescent↗
PubMed1999

The role of Pax6 in restricting cell migration between developing cortex and basal ganglia.

It is not clear to what extent restricted cell migration contributes to patterning of the developing telencephalon, since both restricted and widespread cell migration have been observed. Here, we have analysed dorso-ventral cell migration in the telencephalon of Pax6 mutant mice (Small Eye). The transcription factor Pax6 is expressed in the dorsal telencephalon, the cerebral cortex. Focal injections of adenoviral vectors containing the green fluorescent protein were used to follow and quantify cell movements between two adjacent regions in the developing telencephalon, the cerebral cortex and the ganglionic eminence (the prospective basal ganglia). The analysis in wild-type mice confirmed that the cortico-striatal boundary acts as a semipermeable filter and allows a proportion of cells from the ganglionic eminence to invade the cortex, but not vice versa. Ventro-dorsal cell migration was strongly enhanced in the Pax6 mutant. An essential function of Pax6 in the regionalisation of the telencephalon is then to limit the invasion of the cortex by cells originating in the ganglionic eminence. Cortical cells, however, remain confined to the cortex in the Pax6 mutant. Thus, dorsal and ventral cells are restricted to their respective territories by distinct mechanisms.

Adenoviridae↗
PubMed1998

Measurement of forearm bone mineral density: comparison of precision of five different instruments.

Measurement of bone mineral density (BMD) is used for clinical estimation of fracture risk in osteoporosis. The precision of the method is important for the evaluation of true and clinical relevant changes in BMD in patients with osteoporosis. We measured BMD of the forearm in 14 young, healthy probands (10 males, 4 females), aged 24. 6 +/- 1.5 years with five different instruments using dual-energy X-ray absorptiometry (DXA), single-photon absorptiometry (SPA), and peripheral quantitative computed tomography (pQCT). Precision was expressed as the percentage coefficient of variation (CV%). In addition, the standardized CV% (sCV%) and the root mean square standard deviation (rmsSD%) was calculated for long-term precision. CV% ranged from 1.04 (SPA, distal BMD) to 2.75% (pQCT, trabecular BMD) for short-term precision and from 1.49 (DXA, QDR 1000, 1/3-distal BMD) to 4.33% (SPA, ultradistal) for long-term precision, respectively. The results for the rmsSD% were higher but correlated well with the CV%. A change that exceeds 2 radical2 CV% has been considered as being significant. On this basis, 24.0 +/- 5.1% (mean +/- SEM) of the participants in our study would be expected to have a significant change in BMD without any correlation to the time-delay between the two measurements. Measurements of BMD were done at two locations with all five instruments: ultradistal and middistal BMD using DXA and SPA and total and trabecular BMD using pQCT, respectively. Coefficients of correlation for "between-instrumental" correlation were greater than 0.5 for almost all instruments. Distal and ultradistal BMD measured by SPA and trabecular and total BMD measured by pQCT correlated better with ultradistal BMD measured by DXA. Correspondingly, "within-instrumental" correlation was better for pQCT and SPA than for DXA. The coefficients of correlation between the different DXA methods were greater than 0.95 when corresponding locations were compared. We conclude that the clinical value of monitoring bone loss by measurement of forearm BMD is compromised by the low precision which was seen for DXA methods as well as for SPA and even pQCT in young healthy controls.

Absorptiometry, Photon↗
PubMed1998

Sequence comparison of the chromosomal regions encompassing the internalin C genes (inlC) of Listeria monocytogenes and L. ivanovii.

We have recently cloned and characterized the inlC gene of Listeria monocytogenes which belongs to the listerial internalin multigene family and codes for a 30-kDa secreted protein containing five consecutive leucine-rich repeats. Here, we show that in L. monocytogenes inlC is located between the rplS gene (encoding the 50S ribosomal protein L19), and the infC gene (encoding the translation initiation factor 3). By direct and inverse polymerase chain reactions (PCR), we cloned a 5.4-kb region containing a homologous gene (termed i-inlC) from L. ivanovii, the other pathogenic member of the genus Listeria. In this microorganism, the i-inlC gene is preceded by another internalin gene, i-inlD, which seems to be specific for L. ivanovii, as this gene could not be detected in L. monocytogenes by Southern hybridization with an i-inlD gene probe. The i-inlD gene also encodes a small secretory internalin (i-InlD), which shares extended homology with (i-)InlC. Upstream of i-inlD are genes for 23S rRNA and 5S rRNA, and two tRNA genes [Asn-tDNA (GTT) and Thr-tDNA(GTT)]. The 3' terminus of the Thr-tRNA gene appears to be the site of an insertion of a genetic element including i-inlC and i-inlD. A putative transcriptional regulator gene, the product of which contains the TetR family signature, is located downstream of i-inlC. This chromosomal position of the two inlC genes on their respective chromosomes may be due to horizontal transfer of this gene. Transcription of i-inlC and i-inlD is strictly dependent on the transcriptional activator PrfA, which regulates transcription of most of the known virulence genes (including inlC) of L. monocytogenes and of L. ivanovii.

Amino Acid Sequence↗
PubMed1998

Pax6 controls radial glia differentiation in the cerebral cortex.

Radial glia cells perform a dual function in the developing nervous system as precursor cells and guides for migrating neurons. We show here that during forebrain neurogenesis, the transcription factor Pax6 is specifically localized in radial glia cells of the cortex but not of the basal telencephalon. In Pax6-deficient mice, cortical radial glia cells were altered in their morphology, number, tenascin-C (TN-C) expression, and cell cycle. We show that some of these alterations are cell-autonomous, whereas others were rescued by coculturing with wild-type cortical cells. Our results suggest that Pax6 plays an essential role in the differentiation of cortical radial glia. Thus, despite their widespread distribution, radial glia cells are regionally specified in the developing CNS.

Animals↗
PubMed1998

Theory of mind and psychoses.

BACKGROUND: A cardinal feature of schizophrenia is the sufferer's difficulty in interacting appropriately within the social milieu. This deficit has recently been associated with the concept of theory of mind, more commonly constructed as a working model to understand behavioural patterns in autistic children. In this paper the complex relationships between theory of mind, IQ and psychoses are addressed. METHODS: Five experimental groups were used; non-psychiatric controls, affective disorder, schizophrenia with normal pre-morbid IQ, schizophrenia with pre-morbid IQ in the mildly learning disabled range, and mild learning disability with no history of psychiatric illness. All subjects were given a first order Theory of Mind Task and if successful, a second order Theory of Mind Task was then administered. All subjects were rated using the Positive and Negative Symptom Scale (PANSS). RESULTS: Subjects with schizophrenia and subjects with mild learning disability show impaired ability on a second order theory of mind task. However, when patients who are unable to answer reality questions are removed from the analysis specific impairment of theory of mind is only seen in subjects with schizophrenia. Furthermore, this impairment is relatively specific to particular psychopathological clusters in subjects with schizophrenia. Even though the same clusters of psychopathology are also seen in patients with affective disorder, their presence is not associated with poor second order theory of mind performance. CONCLUSIONS: Impaired theory of mind on second order tests is specific to schizophrenia when compared to mild learning disability and affective disorder control groups. Subjects with schizophrenia and pre-morbid mild learning disability show greater impairment than subjects with schizophrenia and a pre-morbid IQ within the normal range.

Adult↗
PubMed1998

Identification of allergens in oilseed rape (Brassica napus) pollen.

BACKGROUND: Pollen from oilseed rape (OSR), Brassica napus, an increasingly cultivated oilplant from the Brassicaceae, has been recognized as a potential cause of allergic sensitization. Allergens have been hardly investigated. METHODS: We characterized IgE binding proteins in OSR pollen by immunoblot, immunoblot inhibition and specific monoclonal antibodies using sera from 89 patients sensitized to OSR. RESULTS: Two low-molecular-weight allergens of 6/8 kD and 14 kD as well as a high molecular-weight cluster (27-69 kD) comprising six cross-reactive peptides could be identified. The three allergens were recognized by 50, 34 and 80% of patients, respectively. Immunoblot IgE binding to OSR could be totally inhibited by rye pollen and moderately by birch pollen (6/8 and 14 kD) while mugwort had little effect. An anti-profilin-specific monoclonal antibody bound specifically to a 14-kD protein in OSR. Binding to the 6/8-kD rape allergen could be effectively inhibited by rAln g 2, a calcium-binding protein from alder. Periodate treatment led to a significant reduction in IgE binding to the 27 to 69-kD OSR allergens indicating that carbohydrate determinants are involved in IgE binding. OSR proteins were capable to quench IgE binding to timothy grass pollen proteins of >/=60 kD suggesting that grass pollen group 4 allergens cross-react with the 27 to 69-kD cluster in OSR. CONCLUSIONS: The data demonstrate that OSR pollen is allergenic and indicate that the identified allergens represent cross-reacting homologues of well-known pollen allergens, i.e. calcium-binding proteins, profilins, and high-molecular-weight glycoproteins. Via cross-reactivity, exposure to OSR pollen may be a prolonging and aggravating factor in underlying birch and grass pollen allergy.

Allergens↗
PubMed1998

Transmitting transmitter phenotypes in brain development.

Little is known about the transmitter choice of neurons in the central nervous system. Recent evidence suggests that precursor cells in the mammalian neocortex are multipotential and generate GABAergic as well as glutamatergic neurons. Environmental interactions within the proliferative zone seem to specify the transmitter phenotype of the neurons generated by the multipotential precursor cells. Precursor cells are restricted in the ventricular zone of a given region in the forebrain and do not intermingle with precursor cells from the adjacent regions. They are thus exposed to distinct region-specific environmental influences that instruct the different neuronal phenotypes found in different regions of the adult brain. Amongst the factors that influence the transmitter choice of early neuroblasts are transmitters themselves. Activity-dependent mechanisms mediated by a variety of neurotransmitters and their receptors could be the key players in specifying neuronal phenotypes at early developmental stages in the ventricular zone.

Animals↗
PubMed1997

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↗
PubMed1997

The Listeria monocytogenes iap gene as an indicator gene for the study of PrfA-dependent regulation.

The iap gene of Listeria monocytogenes encodes the extracellular protein p60, which possesses a murein hydrolase activity necessary for septum separation. We constructed L. monocytogenes EGD strains harbouring plasmids that carry the iap gene under the control of the PrfA-regulated promoters of the L. monocytogenes genes hly, mpl, and actA. After insertional inactivation of the chromosomal iap gene in L. monocytogenes EGD, p60 synthesis was strictly dependent on PrfA. Elevated temperature (40 degrees C) enhanced synthesis of p60 in L. monocytogenes when the iap gene was under the control of the hly promoter; this appeared to be associated with increased synthesis of PrfA at this temperature. Synthesis of p60 in L. monocytogenes was significantly lower when the iap gene was placed under the control of the actA or the mpl promoter. Transcription of the iap gene was repressed in L. monocytogenes in the presence of PrfA when iap expression was under the control of the prfA promoter P2. Under the control of the hly promoter the gene produced low levels of secreted p60 in the presence of low amounts of PrfA, and this in turn led to the generation of long listerial cell filaments consisting of bacteria that had failed to separate. Overexpression of p60 in the presence of high levels of PrfA caused formation of single cells, which showed reduced viability depending on the level of secreted p60. These data suggest that the iap gene may be a valuable tool for monitoring virulence gene regulation by PrfA under in vivo conditions, without disturbing the integrity of the infected host cells.

Bacterial Proteins↗