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Biomedical subjects

P Winkler

Publications and source records attributed to P Winkler.

At least 19 recordsLinked to original sources
PubMed1999

Different effects of bone morphogenetic proteins 2, 4, 12, and 13 on the expression of cartilage and bone markers in the MC615 chondrocyte cell line.

In order to study the lineage leading to chondrocyte and osteoblast phenotype in vertebrate development, we examined the effect of recombinant human bone morphogenetic protein (BMP)-2, BMP-4, BMP-12 [or growth and differentiation factor (GDF)-7], and BMP-13 (or GDF-6) on the phenotypic expression of the mouse chondrocyte cell line MC615, grown for 1 or 2 weeks in monolayer. Protein synthesis rates were monitored after incubation with [(14)C]proline. BMP-2 and BMP-4 increased protein synthesis, in agreement with our observation by phase-contrast microscopy of a highly refractile matrix around MC615 cells treated with BMP-2 and -4. Markers of the chondrocytic and osteoblastic differentiation were analyzed at mRNA level. Expression of the type II collagen gene, a marker of the cartilage phenotype, was up-regulated in the presence of low concentration of BMP-2 or -4 (50 ng/ml) and down-regulated at higher concentrations (100-400 ng/ml). In parallel, this expression was stable in the presence of BMP-12 or -13 in the dose range tested (50-400 ng/ml). Expression of the matrix Gla protein (MGP) gene, another marker of cartilage, was also reduced in the presence of 100 ng/ml BMP-2 or -4, while it remained stable in the presence of BMP-12 or -13 at the same concentration. In contrast, expression of the bone Gla protein (BGP) gene, or osteocalcin, a marker of the bone phenotype, was induced when the cells were treated with BMP-2 or -4 but was not detected when the cells were treated with BMP-12 or -13. At the same time, BMP-2 or -4 markedly up-regulated expression of type X collagen mRNA, indicating that MC615 cells possess the ability to express traits associated with endochondral ossification, when exposed to specific BMPs. Furthermore, detailed analysis of type II collagen expression showed that the alternatively spliced transcript collagen IIB, specific for cartilage, is expressed concomitantly with BGP. Therefore, MC615 chondrocytes can simultaneously express chondrocytic and osteoblastic markers, in response to BMP-2 or -4, but show minimal response to BMP-12 (or GDF-7) or to BMP-13 (or GDF-6). These results raise the possibility that chondrocytes in vivo can express osteoblastic properties, provided they are induced by BMP-2 or -4.

Animals↗
PubMed1999

DNA analyses support the hypothesis that infanticide is adaptive in langur monkeys.

Although the killing of dependent infants by adult males is a widespread phenomenon among primates, its causes and consequences still remain hotly debated. According to the sexual selection hypothesis, infanticidal males will gain a reproductive advantage provided that only unrelated infants are killed and that the males increase their chances of siring the next infants. Alternatively, the social pathology hypothesis interprets infanticide as a result of crowded living conditions and, thus, as not providing any advantage. Based on DNA analyses of wild Hanuman langurs (Presbytis entellus) we present the first evidence that male attackers were not related to their infant victims. Furthermore, in all cases the presumed killers were the likely fathers of the subsequent infants. Our data, therefore, strongly support the sexual selection hypothesis interpreting infanticide as an evolved, adaptive male reproductive tactic.

Adaptation, Biological↗
PubMed1999

18F-FDG PET studies in patients with extratemporal and temporal epilepsy: evaluation of an observer-independent analysis.

UNLABELLED: The aim of this study was to evaluate an observer-independent analysis of 18F-fluorodeoxyglucose (FDG) PET studies in patients with temporal or extratemporal epilepsy. METHODS: Twenty-seven patients with temporal epilepsy and 22 patients with extratemporal epilepsy were included in the study. All patients with temporal epilepsy and 7 patients with extratemporal epilepsy underwent surgical treatment. In patients who showed significant postoperative improvement (temporal, n = 23; extratemporal, n = 6), the epileptogenic focus was assumed to be located in the area of surgical resection. In extratemporal epilepsy patients who did not undergo surgery, the focus localization was determined using a combination of semiology, ictal and interictal electroencephalography, [99mTc]ethyl cysteinate dimer SPECT, MRI and [11C]flumazenil PET. Visual analysis was performed by two experienced and two less experienced blinded observers using sagittal, axial and coronal images. In the automated analysis after anatomic standardization and generation of three-dimensional stereotactic surface projections (SSPs), a pixelwise comparison of 18F-FDG uptake with an age-matched reference database (n = 20) was performed, resulting in z score images. Pixels with the maximum deviation were detected, summarized and attached to one of 20 predefined surface regions of interest. For comparison with 18F-FDG PET and MR images, three-dimensional overlay images were generated. RESULTS: In patients with temporal epilepsy, the sensitivity was comparable for visual and observer-independent analysis (three-dimensional SSP 86%, experienced observers 86%-90%, less experienced observers 77%-86%). In patients with extratemporal epilepsy, three-dimensional SSP showed a significantly higher sensitivity in detecting the epileptogenic focus (67%) than did visual analysis (experienced 33%-38%, each less experienced 19%). In temporal lobe epilepsy, there was moderate to good agreement between the localization found with three-dimensional SSP and the different observers. In patients with extratemporal epilepsy, there was a high interobserver variability and only a weak agreement between the localization found with three-dimensional SSP and the different observers. Although three-dimensional SSP detected multiple lesions more often than visual analysis, the determination of the highest deviation from the reference database allowed the identification of the epileptogenic focus with a higher accuracy than subjective criteria, especially in extratemporal epilepsy. CONCLUSION: Three-dimensional SSP increases sensitivity and reduces observer variability of the analysis of 18F-FDG PET images in patients with extratemporal epilepsy and is, therefore, a useful tool in the evaluation of this patient group. The benefit of this analytical approach in patients with temporal epilepsy is less apparent.

Adolescent↗
PubMed1998

Amplification of microsatellites adapted from human systems in faecal DNA of wild Hanuman langurs (Presbytis entellus).

Microsatellite systems originally established for human DNA were utilized for paternity testing from faecal DNA in a natural population of Hanuman langurs (Presbytis entellus). Thirty-two primer pairs were applied to amplify DNA obtained from langur faeces. Twenty-two of these primer pairs yielded specific amplification products and 11 loci were polymorphic. Allele distributions and heterozygosity rates were determined for five systems. Genetic information from these five systems was sufficient for paternity exclusion in 46 out of 52 cases. Results were consistent enough to allow genotyping from faeces, although sometimes only one allele was amplified in a heterozygous individual. In conclusion, relationship analyses from faeces are possible in spite of the evolutionary distance between humans and langurs.

Animals↗
PubMed1998

Advances in paediatric CNS ultrasound.

Advanced paediatric ultrasound of the central nervous system (CNS) requires 7 MHz sector and linear transducers, equipment which is highly sensitive to flow velocity (Power Doppler) and additional transcranial axial, coronal and sagittal imaging. New diagnostic possibilities include recognition of subarachnoid hemorrhage (imaging of cisterns and/or CSF-flow); differentiation between subarachnoid and subdural fluid collections (colour flow imaging of traversing veins); additional criteria suggestive of spinal cord tethering (spinal cord pulsations); and grey-white matter differentiation in newborn infants. A meticulous examination technique is mandatory when investigating suspected brain death, sinus venous thrombosis, diffuse early ischemia or viral (herpes) encephalitis. Anatomical areas such as the cerebral aqueduct, tentorium, Foramina of Luschka or circle of Willis which are not usually regarded as accessible to cerebral echography can be visualized by advanced transcranial imaging technique. Indications for transcranial scanning; shortcomings of cerebral ultrasound; measures to overcome limitations; and requirements for present and future ultrasound equipment are given and discussed in tables.

Brain Diseases↗
PubMed1997

The uretero-vesical jet as a functional diagnostic tool in childhood hydronephrosis.

Childhood hydronephrosis (HN) is accurately detected by ultrasound (US), but its functional work-up remains a domain of scintigraphy, the Whitaker-test, and clinical follow-up. We utilized color doppler US (CD-Jet) of uretero-vesical jets (UVJ) to visualize the post-obstructive ureteral flow in childhood HN. A total of 177 standardized CD-Jet were performed in 132 children aged 1 day to 14.9 years. Sixty-nine investigations in 43 patients with unilateral HN were compared with a standardized technetium 99m-mercaptotriacetylglycine nephrogram; in 10 infants both procedures were performed consecutively on the same day. UVJ were visible in 96% of all investigations. Ureteral obstruction resulted in absence of UVJ in 85% of examinations; in the remaining 15% the jet frequency was less than 10% observed in the contralateral control. Results are highly significant in both uretero-pelvic (P < 0.00007) and uretero-vesical lesions (P < 0.00005, Wilcoxon test) and are reproducible in sequential investigations. In nonobstructive distal HN the jet frequency averaged 70% of the unaffected side (P < 0.05). In proximal lesions it is equal. Jet evaluation in reflux nephropathy did not differ from controls. Compared with scintigraphy, CD-US identifies obstruction with a specificity of 94.2% and sensitivity of 94.8%. CD-US of UVJ therefore may serve as a reliable screening parameter in unilateral childhood HN.

Adolescent↗
PubMed1997

Localization of the motor hand area to a knob on the precentral gyrus. A new landmark.

Using functional magnetic resonance imaging (fMRI) we have evaluated the anatomical location of the motor hand area. The segment of the precentral gyrus that most often contained motor hand function was a knob-like structure, that is shaped like an omega or epsilon in the axial plane and like a hook in the sagittal plane. On the cortical surface of cadaver specimens this precentral knob corresponded precisely to the characteristic 'middle knee' of the central sulcus that has been described by various anatomists in the last century. We were then able to show that this knob is a reliable landmark for identifying the precentral gyrus directly. We therefore conclude that neural elements involved in motor hand function are located in a characteristic 'precentral knob' which is a reliable landmark for identifying the precentral gyrus under normal and pathological conditions. It faces and forms the 'middle knee' of the central sulcus, is located just at the cross point between the precentral sulcus and the central sulcus, and is therefore also visible on the cortical surface.

Aged↗
PubMed1996

Tumor size and prognosis in aggressively treated osteosarcoma.

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.

Adolescent↗
PubMed1995

Correlation of histological tumor vascularization and Doppler sonography in patients with malignant melanoma of the choroid.

BACKGROUND: In previous studies Doppler sonography was proven to the useful for diagnostics and follow-up of malignant melanomas of the choroid. METHODS: To evaluate the correlation between Doppler sonographical findings and the histological tumor vascularization, we examined five eyes of five patients with malignant melanoma of the choroid before enucleation with an ATL Ultramark-8 Duplex scanner and compared these results with computerized planimetry of histological tumor vascularization after immunohistochemical staining of vascular endothelium with anti-factor-VIII antibodies. RESULTS: We found no definite correlation of flow velocities with histological parameters of tumor vascularization. The tendency was for a decrease in maximum flow velocities as histological vascularization increased. CONCLUSIONS: Due to (1) the usual lack of sensitivity parameters of the used Duplex device for the clinical user and (2) the unpredictable branching pattern within a melanoma resulting in an unknown angle of incidence of the Doppler beam, we conclude that the quantitative results of Doppler sonography require cautious interpretation. Nevertheless, presence or absence of Doppler shifts is a valuable parameter for the follow-up of irradiated tumors.

Blood Flow Velocity↗
PubMed1994

Cerebrospinal fluid dynamics in infants evaluated with color Doppler US and spectral analysis: respiratory versus arterial synchronization.

PURPOSE: To investigate rapid cerebrospinal fluid (CSF) dynamics in infants in relation to respiration and cardiac cycle. MATERIALS AND METHODS: CSF-flow signals were detected in 35 of 526 consecutive infants (22 male and 13 female infants, aged 1-30 days) who underwent 140 color flow and pulsed Doppler ultrasonographic studies at the cerebral aqueduct. In infants with spontaneous CSF flow, Doppler spectrum and respiratory signal or electrocardiogram were recorded simultaneously. RESULTS: In 64 examinations performed in 20 infants, CSF flow was induced by abdominal pressure change only. Among 76 examinations performed in 15 infants, CSF flow was synchronous to spontaneous respiration in 28 examinations, to mechanical ventilation in nine, to the cardiac cycle in 15, and to both respiratory and heart rates in 24. CONCLUSION: Respiration-modulated CSF flow predominates in infants without significant intracranial disease. Pulsation or CSF solely or mainly synchronous to the cardiac cycle is associated with conditions causing increased intracranial pressure.

Abdomen↗
PubMed1994

Cerebrospinal fluid dynamics in infants evaluated with echographic color-coded flow imaging.

PURPOSE: To use color Doppler flow ultrasonography (US) for investigation of rapid regional motion of cerebrospinal fluid (CSF) in infants with subarachnoid hemorrhage or meningitis. MATERIALS AND METHODS: Sixty-four transfontanellar and transcranial color Doppler US scans of the cerebral aqueduct, ventricles, and basal cerebral and spinal subarachnoid spaces were obtained in 19 infants (12 male and seven female infants, aged 1-81 days). Abdominal palpation or periods of straining or crying were used to increase velocity of CSF motion. RESULTS: In all 19 infants, rapid to-and-fro color CSF flow was observed in the aqueduct. Color-coded CSF flow signals were seen in the aqueduct in 19 infants, in the third (n = 17 with jetlike flow) and fourth (n = 7 with jets) ventricles in 17, at the foramen of Magendie in 11 (n = 4 with jets), and in the spinal compartment in 14. CONCLUSION: In the presence of scattering particles or cells, regional CSF flow can be investigated with transfontanellar, transcranial, and spinal color flow imaging. Results of regional echographic CSF flow investigation can indicate recent subarachnoid hemorrhage or exclude obstruction. Jetlike CSF flow might stimulate new concepts of rapid CSF dynamics.

Cerebral Hemorrhage↗
PubMed1994

[Results of serological studies of Leptospira antibodies in foxes].

1253 serum samples of foxes were checked for the presence of Leptospira antibodies. 24 serum samples (1.92%) were positive. Leptospira grippotyphosa (10 samples) was the most common serotype, which ist also widespread in other wild and domestic animals. The possibility of distribution of Leptospira in fox populations are discussed. Leptospira antibodies were found in only 0.20% of the examined serum samples of domestic animals of the same territory (South-Thuringia).

Animals↗
PubMed1992

Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF) in meningitis and hemorrhage. Part I. Clinical evidence.

Using echographic flow imaging (colour Doppler), flow within ventricular CSF-pathways was discovered in an infant with purulent meningitis. 22 mature and 40 premature infants were then investigated for presence of CSF-flow which was detected in a further 5 infants, all premature. Diagnostic criteria for echographic CSF-flow imaging are: 1. flow signals "within" CSF-pathways; 2. to-and-fro movement of CSF (spectral analysis); 3. specific response of CSF-flow to stimuli (respiration, crying, abdominal palpation); 4. dynamic CSF-imaging related to specific anatomical areas of intracranial CSF-pathways. Echographic detection of CSF-flow depends on optimized adjustment of controls, equipment used, meticulous examination technique and awareness of pitfalls on the part of the examiner. A further prerequisite is the presence of scattering particles within CSF, such as red or white blood cells (minimum concentration in the order of one thousand cells/microL) or air. Although echographic CSF-flow imaging is not applicable for excluding the presence of disease, it appears to be a new diagnostic tool with considerable potential allowing selected early and non-invasive diagnosis of CSF-pathology and giving new insights into CSF-hemodynamics.

Abdomen↗