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Biomedical subjects

H Kurz

Publications and source records attributed to H Kurz.

At least 37 records · Page 2Linked to original sources

Impulsive excitation of phonon-pair combination states by second-order raman scattering

The excitation of (100)-oriented KTaO3 with 25-fs laser pulses impulsively drives phonon-pair combination states via second-order Raman scattering. Oscillations in the phonon-amplitude covariance at the sum and difference frequency of the two involved phonons are observed in a spectrally and temporally resolved pump-probe experiment. Transmission changes of the sample are dominated by contributions of wave vector conserving phonon-pair combinations from the entire Brillouin zone that have maxima in their combined density of states. For low temperatures the temperature dependence of the covariance oscillations of different phonon combinations is reproduced by a quantum-mechanical model.

Journal Article↗

Active interaction of human A375 melanoma cells with the lymphatics in vivo.

We have used the avian chorioallantoic membrane (CAM) to study the interaction of tumor cells with the lymphatics in vivo. The vascular endothelial growth factor-C (VEGF-C) has been shown to be lymphangiogenic. We have therefore grown VEGF-C-expressing human A375 melanoma cells on the CAM. These tumors induced numerous lymphatics at the invasive front, and compressed or destroyed VEGF receptor (R)-3-positive lymphatics were observed within the solid tumors. The lymphatics in the CAM and in the A375 melanomas could also be demonstrated with an antibody against Prox 1, a highly specific marker of lymphatic endothelial cells. Proliferation studies revealed a BrdU labeling index of 11.6% of the lymphatic endothelial cells in the tumors and at their margins. A great number of melanoma cells invaded the lymphatics. Such interactions were not observed with VEGF-C-negative Malme 3 M melanoma cells. Lymphangiogenesis was inhibited to some extent when A375 melanoma cells were transfected with cDNA encoding soluble VEGFR-3 (sflt4), and the BrdU labeling index of the lymphatics in these tumors was 3.9%. Invasion of lymphatics and growth of blood vascular capillaries were not inhibited by the transfection. Therefore, tumor-induced lymphangiogenesis seems to be dependent to some extent on VEGF-C/flt4 interactions, but invasion of lymphatics seems to be a distinct mechanism.

Allantoin↗

Induction of the blood-brain barrier marker neurothelin/HT7 in endothelial cells by a variety of tumors in chick embryos.

Neurothelin/HT7, a transmembrane glycoprotein of the immunoglobulin superfamily, is a marker of blood-brain barrier (BBB)-forming endothelial cells. We have studied the expression of neurothelin in tumors grown on the chorioallantoic membrane (CAM) of chick embryos. We inoculated each 3-5 x 10(6) rat C6 glioma, rat 10AS pancreatic carcinoma, human A375 melanoma, and human mammary duct adenoma cells on the CAM of 10-day-old chick embryos. The tumors were harvested on day 17. All four tumor cell lines formed solid tumors which were supplied by vessels of CAM origin. Foci of bleeding were regularly observed within the tumors. All four tumors induced the expression of neurothelin/HT7 (but not of glucose transporter-1) in tumor endothelial cells, whereas expression in adjacent endothelial cells of normal CAM did not occur. Confocal laser scanning microscopy revealed that the pattern of neurothelin expression in tumor endothelial cells was different from that in normal central nervous system (CNS) endothelium, but the relative molecular weight of neurothelin, studied by western blot analysis, was the same in brain and in tumors. It has been shown that, with increasing malignancy, vessels of CNS tumors lose their morphological characteristics, and BBB markers such as the glucose transporter-1 are downregulated. Our results show that, in contrast, the BBB marker, neurothelin, is expressed de novo in tumor endothelial cells. Potential common functions of neurothelin in endothelial cells of the CNS and tumors are discussed.

Allantois↗

Three-dimensional analysis of DNA replication foci: a comparative study on species and cell type in situ.

Chromatin morphology of interphase nuclei in most cell lines of quail (Coturnix coturnix japonica) and chick (Gallus gallus domesticus) embryos shows typical interspecies differences. This intrinsic marker has been used in quail/chick chimerisation experiments, where also differences between cell types were noted. We asked whether similar differences between species and between cell types could be observed in S phase nuclei in situ. In this report, we used bromodeoxyuridine (BrdU) pulse labelling and anti-BrdU immunofluorescence to detect DNA replication foci in the nuclei of identified cells. In the central nervous system of 5- to 7-day-old quail and chick embryos, mesoderm-derived cells with strikingly different morphology and topographical distribution were studied: endothelial, i.e. polarised cells forming continuous tubes, and macrophages, i.e. non-polarised, ameboid or ramified individual cells. Using confocal microscopy, replication foci in the nuclei were assessed quantitatively and three-dimensional visualisations were produced. We consistently observed that: (1) chick, but never quail, nuclei displayed completely confluent replication sites, independent of cell type, and (2) macrophages, but not endothelial cells, had distinct perinucleolar replication sites, independent of species. We thus demonstrate a new relationship between cell type and spatial arrangement of DNA replication sites, and conclude that interspecies differences of chromatin distribution are conserved throughout S phase. Our results strongly recommend that work done on nuclear structure in vitro should not be extrapolated without reservation to cells in vivo.

Animals↗

Formation of Ordered Nanoscale Semiconductor Dots by Ion Sputtering.

A formation process for semiconductor quantum dots based on a surface instability induced by ion sputtering under normal incidence is presented. Crystalline dots 35 nanometers in diameter and arranged in a regular hexagonal lattice were produced on gallium antimonide surfaces. The formation mechanism relies on a natural self-organization mechanism that occurs during the erosion of surfaces, which is based on the interplay between roughening induced by ion sputtering and smoothing due to surface diffusion.

Journal Article↗

Inhalation devices for the treatment of asthma--how much do paediatricians know about their correct use?

The present study was undertaken to assess the practical and theoretical knowledge of paediatricians in regard of inhalation devices for the treatment of childhood asthma. Forty-one paediatricians (39 from different parts of Austria and 2 from Switzerland), all of them running hospital-based chest clinics, were tested in regard of 4 items (Diskhaler, Metered dose inhaler (MDI) with Aerochamber, cleaning of an Aerochamber and a Pari Junior jet nebuliser). Practical performance and theoretical knowledge were assessed. Scoring was done by one consultant using a score of 1-5, with 1 point being given for the poorest performance and 5 points for the best. Overall performance was acceptable with a median of 13 points (the maximum achievable score was 20), but there were some deficits in the practical use of special devices. Better training on the use of different devices for inhalation therapy of asthmatic children is desirable.

Adult↗

[Long central apnea as the chief symptom of aseptic meningoencephalitis in a 6-week-old infant].

Viral infections can cause apnoea, bradycardia, and desaturation events in preterm and new born infants. These symptoms do not always occur in older infants. A link between virus infection, apnoea, apparent life threatening events (ALTE) and sudden infant death (SID) is speculated. We report a 6-week-old infant with long central apnoea as the first and main symptom of meningoencephalitis caused by enterovirus.

Enterovirus Infections↗

Resolution of obstructive sleep apnea syndrome after adenoidectomy in congenital central hypoventilation syndrome.

We report on a 2 1/2-year-old boy who is currently ventilated at home by positive pressure ventilation through a nasal mask during the night because of congenital central hypoventilation syndrome (CCHS). Up to age 2 he had developed normally. A reevaluation was performed because of symptoms suggestive of obstructive sleep apnea syndrome (OSAS), including snoring, nocturnal sweating, frequent nighttime awakenings, speech impairment, daytime fatigue, and failure to thrive. A sleep study indicated obstructive apnea episodes lasting up to 40 s and arterial desaturations below 50% during spontaneous sleep. During mechanical ventilation snoring persisted, and capillary PCO2 rose to 60 mm Hg. Partial upper airway obstruction, leaking around the mask, and arousal movements developed on passive flexion of the neck to 20 degrees. After adenoidectomy, symptoms of OSAS resolved. There were no more obstructive apneas during spontaneous sleep, but obstructive apneas could be provoked by neck flexion to 20 degrees. During ventilation, neck flexion of 20 degrees was tolerated, but a 40 degrees flexion led to partial obstruction. In CCHS patients, the problem of upper airway obstruction is rarely noted because most patients are ventilated through a permanent tracheostomy. Today, noninvasive ventilation strategies are becoming more common. Reduced activity of upper airway muscles and impaired reflex mechanisms could lead to upper airway obstruction during face mask positive pressure ventilation in children with CCHS. Enlarged adenoids worsened this problem in our patient, leading to insufficient ventilation and OSAS. Adenoidectomy resolved symptoms of OSAS and enabled successful nasal mask ventilation. Close follow-up of the patient avoided hypoxia and sequelae from OSAS such as pulmonary hypertension.

Adenoidectomy↗

Lack of correlation between placenta and offspring size in mouse interspecific crosses.

The placenta plays a pivotal role in fetal growth control and is considered a major site of genetic conflict between maternal and paternal genomes within the conceptus and, in addition, the genome of the mother. Accordingly, placental development is a strictly controlled process, and both placental and fetal weights do not vary much in intraspecific crosses of laboratory mice (Mus musculus). In mouse interspecific crosses and backcrosses [(M. musculus x M. spretus) x M. musculus], tremendous variation of placental, but not of fetal weight was observed. We have studied trophoblast cell type distribution and differentiation, and their effect on the associated placentas and fetuses in such backcrosses. Differentiation of spongious trophoblast, but not size of materno-fetal interface, correlated with fetal weight. Giant fetuses were observed only if less than one third of the spongiotrophoblast was formed by glycogen cells. Thus, placental efficiency was inversely related to the amount of glycogen cells. This influence of a trophoblast-derived cell type on fetal growth was not anticipated. We conclude that: (1) glycogen cells are able to negatively modulate fetal growth by an as yet unidentified mechanism; (2) correlation between fetal and placental weights is weak or absent in interspecific hybrids; (3) impaired control over placental and embryonic development in hybrids may contribute to post-mating isolation of species.

Animals↗

Influence of nasopharyngeal CPAP on breathing pattern and incidence of apnoeas in preterm infants.

Continuous positive airway pressure (CPAP) applied by endotracheal (ET) tube in the pharynx (nasopharyngeal CPAP, n-CPAP) is widely used for the treatment of mild respiratory distress syndrome and of apnoeas of prematurity. Effects on breathing pattern and on different types of apnoeas are not fully understood. We wanted to know the effect of discontinuing n-CPAP on the respiratory rate, apnoeas and bradycardia/desaturation events. Thirteen prematurely born infants with bradycardia and/or desaturation events were studied when weaning from n-CPAP was clinically considered. Polygraphic studies were performed for 2 h during n-CPAP therapy and for 2 h without CPAP. Nasal flow was measured by registering expiratory pCO(2) at the free nostril opening. During n-CPAP, the respiratory rate was significantly lower, there were fewer obstructive apnoeas, more short central apnoeas (6-9 s) and less severe apnoea-associated desaturations. During n-CPAP, the infants spent significantly more time in a state of quiet breathing.

Apnea↗

Automated evaluation of angiogenic effects mediated by VEGF and PlGF homo- and heterodimers.

The effects of growth factors on the blood vessel pattern of chick chorioallantoic membrane (CAM) were assessed with a fast and automated method (extended counting method, XCM; Sandau, 1996) that measures complexity, without assumptions about a fractal structure. XCM is a reliable measure of complexity not only in theory but also in practice: (1) it is robust with respect to thresholding; (2) it shows reduced variance due to pattern translation and rotation; (3) its properties come close to requirements of fractal geometry. It hence is superior to established fractal methods for distinguishing effects induced by various isoforms of vascular endothelial growth factor (VEGF121 and VEGF165), placenta growth factor (PlGF) isoforms, and control treatment. We here show that VEGF homo- and heterodimers and VEGF121/PlGF1 heterodimers increase vascular complexity, whereas PlGF1 and PlGF2 are not effective. PlGF1 and VEGF121 did not mutually influence each other when applied in adjacent fields on the same CAM. Since blood vessels in the CAM originate via nonfractal growth processes, their growth should be analyzed accordingly.

Amnion↗

Platelet-derived growth factor-B induces transformation of fibrocytes into spindle-shaped myofibroblasts in vivo.

Platelet-derived growth factor (PDGF) has a targeted activity on mesenchymal cells, but the in vivo effects of PDGF are not well understood. We have applied about 3 microg of PDGF-A and PDGF-B on the differentiated chorioallantoic membrane (CAM) of 13-day-old chick embryos. After 1-3 days, specimens were evaluated macroscopically, histologically with semi- and ultrathin sections, and immunohistologically with antibodies against smooth muscle alpha-actin (alphaSMA), desmin, and fibronectin (FN). Proliferation studies were performed according to the 5-bromo-2-deoxyuridine (BrdU)/anti-BrdU method. We did not observe effects of PDGF-A. PDGF-B induced proliferation of fibrocytes and their transformation into myofibroblasts. Bundles of spindle-shaped myofibroblasts accumulated beneath the chorionic epithelium. These cells were strongly positive for alphaSMA and FN, but negative for desmin. They possessed a well developed rough endoplasmic reticulum and bundles of microfilaments anchoring in the cell membrane. Our results suggest that PDGF-B is a "transforming" growth factor with important functions during formation of granulation tissue which are closely comparable to the effects of the PDGF-B-like protein of simian sarcoma virus. PDGF-B also induced vascular alterations in the CAM, which, however, appeared to be a secondary effect. While the intra-chorionic capillaries were lost, an accumulation of small vessels positive for alphaSMA was observed. This indicates a function for PDGF-B during segregation of main vessels from a primary vascular plexus.

Actins↗

Embryonic CNS macrophages and microglia do not stem from circulating, but from extravascular precursors.

Invasion of mesoderm-derived cells into the developing spinal cord and brain has been shown to produce early central nervous system (CNS) macrophage and microglia populations in avian embryos. A triplicate mode of entry has been proposed: through the endothelial wall of CNS blood vessels; from the ventricular cavities; and through the pial surface. Invasion of circulating blood cells (monocytes) has not yet been proved in embryonic CNS. This report demonstrates: 1) the use of chick-quail blood chimeras by way of parabiosis (two embryos in one egg); 2) the use of QH1 monoclonal antibody for detection of quail cells circulating in chick blood vessels; 3) the presence of extravascular QH1-positive cells (macrophages) in E7-10 CNS in parabiosis quail, and their absence in parabiosis chick. We conclude that avian macrophages/microglia precursors do not penetrate through the wall of embryonic CNS vessels. In combination with published results, this finding strongly supports the view that invasion of migratory macrophages from the pial surface and proliferation inside the CNS generate all microglia in avian embryos.

Animals↗

Possible role of coagulation factor XIII in the pathogenesis of venous leg ulcers.

BACKGROUND: Aim of this placebo-controlled clinical study was to examine the expression pattern of coagulation factor XIIIa in patients with chronic venous leg ulcers and the impact of a 10 day topical factor XIII treatment on ulcer healing, leg ulcer size and radius reduction. PATIENTS AND METHODS: 24 patients were stratified into two groups, each consisting of 12 patients, with leg ulcers > 1.000 mm2, or < 1.000 mm2. Four patients of each study group were assigned to the control group (n = 8). All leg ulcers were treated by topical application of non-adhering dressings and compression therapy. Patients of the treatment group (n = 16) were treated by additional topical treatment off factor XIII twice daily for ten days. Immunohistochemical staining of leg ulcer specimens before and after treatment (day 10) was performed in all patients. RESULTS: The immunohistochemical staining of factor XIIIa in all specimens before and after therapy showed no significant increase in the expression of factor XIIIa. Comparison of the leg ulcer size, radius and daily radius reduction in the treatment and control group showed no significant differences in values of patients with leg ulcers > 1.000 mm2. However, a decreased leg ulcer size and radius was found in patients of the treatment group with more acute leg ulcers < 1.000 mm2 in contrast to patients with larger leg ulcers (daily ulcer radius reduction from day 0-10; 0.31 mm versus 0.13 mm, p < 0.015). CONCLUSIONS: These results indicate that locally applied factor XIII promotes especially wound healing of more acute smaller venous leg ulcers. Since immunohistochemical staining of factor XIIIa showed no significant differences before and after therapy, we propose that factor XIII is inactivated rapidly after local application on venous leg ulcers.

Administration, Topical↗

Mesoderm-derived cells proliferate in the embryonic central nervous system: confocal microscopy and three-dimensional visualization.

In the chick and quail embryo, two cell populations migrate into the neural tube from the surrounding mesodermal tissues during the fourth day of incubation: individual cells which represent macrophages, and endothelial cells which remain continuous with the extraneural vessels. We report here on the proliferative capacity of these mesoderm-derived cells. A double-immunofluorescence protocol for two monoclonal antibodies of subtype IgG1, the endothelial cell/macrophage marker QH1, and the S-phase marker bromodeoxyuridine, was developed. With confocal laser scanning microscopy of thick microtome sections, labeling indices of intraneural individual QH1-positive cells (12%) and of endothelial cells (10%) were determined. In contrast, the labeling index of extraneural endothelial cells was 25%. With three-dimensional visualization of confocal data, the variable morphology of macrophages was shown. Our results indicate that: (1) proliferative activity of intraneural capillary endothelial cells is less than expected and that it is absent from sprouts; (2) both spheroidal and ramified macrophages proliferate inside the neural tissues; and (3) ramified macrophages frequently make contact with capillary endothelial cells. We conclude that most embryonic microglia may be derived from the early invasive QH1+ macrophages.

Animals↗

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor 1 messenger RNAs in spinal ganglia and sciatic nerve: regulation after peripheral nerve lesion.

In order to determine functional roles of basic fibroblast growth factor (FGF-2) in the peripheral nervous system we have analysed the expression of FGF-2 and FGF receptor 1 (FGFR1) in spinal ganglia and the sciatic nerve under normal conditions and after nerve crush using RNAse protection assay and in situ hybridization. In intact spinal ganglia, both FGF-2 and FGFR1 messenger RNAs are expressed, albeit at different levels. In situ hybridization identifies satellite cells as the source of FGF-2 and sensory neurons as the source of FGFR1 suggesting a paracrine mode of action of FGF-2 on sensory neurons. One day after crush lesion FGF-2 is significantly up-regulated in sensory ganglia L4-L6. Highest levels are found at day 7; control levels are approached after 28 days. FGFR1 messenger RNA, which is strongly expressed in intact spinal ganglia, displays no significant change after lesion. In the intact sciatic nerve, FGFR1 messenger RNA is detected at higher levels than FGF-2 messenger RNA. After injury, both transcripts display a time-dependent up-regulation in both the proximal and distal nerve stump. Schwann cells, as a putative source of the sciatic nerve-derived FGF-2, express both FGF-2 and FGFR1 messenger RNAs in vitro. The FGFR1 transcript level is increased in the presence of forskolin. FGF-2 does not affect expression of FGFR1 messenger RNA but stimulates its own expression. These results show that during peripheral nerve regeneration FGF-2 is up-regulated in both the crushed nerve and the respective spinal ganglia suggesting a possible physiological function of FGF-2 during the regeneration process.

Animals↗

On the bifurcation of blood vessels--Wilhelm Roux's doctoral thesis (Jena 1878)--a seminal work for biophysical modelling in developmental biology.

Wilhelm Roux's doctoral thesis described the relationship between the angle and diameter of bifurcating blood vessels. We have re-read this work in the light of biophysics and developmental biology and found two remarkable aspects hidden among a multitude of observations, rules and exceptions to these rules. First, the author identified the major determinants involved in vascular development; genetics, cybernetics, and mechanics; moreover, he knew that he could not deal with the genetic and regulatory aspects, and could hardly treat the mechanical part adequately. Second, he was deeply convinced that the laws of physics determine the design of organisms, and that a necessity for optimality was inherent in development. We combined the analysis of diameter relationships with the requirement for optimality in a stochastic biophysical model, and concluded that a constant wall-stress condition could define a minimum wall-tissue optimum during arterial development. Hence, almost 120 years after Wilhelm Roux's pioneering work, our model indicates one possible way in which physical laws have determined the evolution of regulatory and structural properties in vessel wall development.

Animals↗