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K Huber

Publications and source records attributed to K Huber.

At least 37 records · Page 2Linked to original sources

Inflammatory cytokines interleukin-6 and oncostatin m induce plasminogen activator inhibitor-1 in human adipose tissue.

BACKGROUND: Adipose tissue is a prominent source of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of plasminogen activation. Increased PAI-1 expression acts as a cardiovascular risk factor, and plasma levels of PAI-1 strongly correlate with body mass index (BMI). Elevated serum levels of interleukin-6 (IL-6), an inflammatory cytokine and a member of the glycoprotein 130 (gp130) ligand family, are found in obese patients and might indicate low-grade systemic inflammation. Another gp130 ligand, oncostatin M (OSM), upregulates PAI-1 in cardiac myocytes, astrocytes, and endothelial cells. We used tissue explants and primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether IL-6 and OSM affect PAI-1 expression in fat. METHODS AND RESULTS: Human subcutaneous and visceral adipose tissue responded to treatment with IL-6 and OSM with a significant increase in PAI-1 production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocyte differentiation was induced by hormone supplementation. All cell types expressed receptors for IL-6 and OSM and produced up to 12-fold increased levels of PAI-1 protein and up to 9-fold increased levels of PAI-1 mRNA on stimulation with IL-6 and OSM. AG-490, a janus kinase/signal transducer and activator of transcription inhibitor, abolished the OSM-dependent PAI-1 induction almost completely. CONCLUSIONS: We have for the first time established a link between the gp130 ligands, the proinflammatory mediators IL-6 and OSM, and the expression of PAI-1 in human adipose tissue. Thus, we speculate that IL-6 and OSM, by upregulating PAI-1 in adipose tissue, can contribute to the increased cardiovascular risk of obese patients.

Adipose Tissue↗

[Current therapeutic options for recurrent respiratory papillomatosis].

The purpose of this review is to describe and to critically discuss recent advances in the management of recurrent respiratory papillomatosis (RRP). The goal of surgery in RRP remains the control of symptoms. A curative therapy cannot be expected. The microdebrider and the CO(2)-laser are currently the most widely used surgical options. Literature reports an increase in adjuvant medical therapies of 10-22%. The most common drugs in adjuvant therapy are interferon, cidofovir and indole-3-carbinole/diindolylmethane. The lack of controlled studies limits our ability to accurately assess the antiviral action of the adjuvant therapies. At the moment, therapeutic interventions remain focused on the surgical removal of papillomas when possible, and additional adjuvant therapy is available for the minority of patients for whom surgical management fails to adequately control their disease. Recent advances in immunologic research offer the hope of immune system modulation as potential future treatment modalities to better control this disease process.

Adult↗

Oxidative stress related markers in the "VITA" and the centenarian projects.

Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Aged↗

The gp130 ligand oncostatin M regulates tissue inhibitor of metalloproteinases-1 through ERK1/2 and p38 in human adult cardiac myocytes and in human adult cardiac fibroblasts: a possible role for the gp130/gp130 ligand system in the modulation of extracellular matrix degradation in the human heart.

There is ample evidence supporting the view that alterations in the balance between matrix deposition and matrix degradation brought about by changes in the respective activities of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) contribute significantly to cardiac dysfunction and disease. Here we show that TIMP-1 was upregulated up to threefold after treatment with the inflammatory mediator and gp130 ligand oncostatin M (OSM) in human adult cardiac myocytes and fibroblasts. The Erk1/2 inhibitor PD98059 and the p38 inhibitor SD202190 abolished the effect of OSM on TIMP-1 production in both cell types. Human cardiac myocytes and human cardiac fibroblasts also express MMP-1, 2, 3 and 9, and TIMP-2 constitutively. OSM, however, did not affect the expression of these proteins. In addition also the other gp130 ligands tested, cardiotrophin-1 (CT-1), interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) had no effect on the expression of TIMPs and MMPs studied. We speculate that OSM by inducing TIMP-1 expression counteracts excessive proteolysis and unrestricted matrix degradation during inflammatory processes in the heart. The notion that OSM favors matrix stabilization in the human heart is further supported by our earlier observation that OSM also upregulates PAI-1, the physiological inhibitor of the protease urokinase-type PA (u-PA), which in turn is essential for extracellular proteolysis. Therefore we propose a role for the gp130 ligand OSM in the modulation of cardiac remodeling and repair processes.

Cells, Cultured↗

[Tonsillotomy with the argon-supported monopolar needle--first clinical results].

BACKGROUND: Primary management of tonsillar hyperplasia in children is tonsillectomy. Recent data from clinical case-series are clearly in support of the hypothesis that tonsillotomy with the CO2-laser seems to be effective and is noted to have less postoperative bleeding and less pain as compared to tonsillectomy. For the first time we used a monopolar argon-supported needle for tonsillotomy in the following study. METHODS: Fifty patients (age: 4.58 years; SD +/- 2.33) with benign tonsillar hyperplasia were recruited. For tonsillotomy we used the monopolar argon-supported needle. The outcome measures were postoperative pain, capability of oral intake, consumption of analgesics and postoperative bleeding. RESULTS: No postoperative bleeding occurred. Post-operative pain hardly occurred and could easily be controlled. The third postoperative day analgesics intake was under one portion per day (mean: 0.91; SD +/- 1.26). Capability of oral intake and swallowing was normal on the seventh postoperative day. CONCLUSION: It was concluded that tonsillotomy, using the monopolar argon-supported needle, is a valid treatment for benign tonsillar hyperplasia in children, which can be performed with slight post-operative pain and a low risk for postoperative bleeding. It offers good dissection and haemostasis abilities. Compared to the CO2-laser the monopolar argon-supported needle does not require any laser safety precautions.

Child↗

Predictive value of plasma plasminogen activator inhibitor-1 for coronary restenosis: dependence on stent implantation and antithrombotic medication.

BACKGROUND: The plasmin activation system is involved in the development of restenosis after percutaneous coronary interventions (PCI). Conflicting data exist concerning the role of plasminogen activator inhibitor-1 (PAI-1) and its predictive value for restenosis. OBJECTIVES: To evaluate the fibrinolytic response to injury after PCI with or without stent implantation on different antithrombotic medications and its relation to late restenosis. PATIENTS AND METHODS: Eighty consecutive patients with successful PCI without (balloon only; n = 37) or with stent implantation (stent; n = 43) on different antithrombotic regimes (balloon only, aspirin; stent, aspirin/coumadin/dipyridamole vs. aspirin/ticlopidine). Blood samples were taken at baseline and up to 7 days after PCI and PAI-1 active antigen and tissue plasminogen activator (t-PA) antigen were determined. Restenosis was angiographically determined after 6 months. RESULTS: PCI increased both t-PA and PAI-1 levels (P < 0.001), with a significant prolonged and pronounced increase in stent vs. balloon-only patients (P < 0.05). Restenosis (stent 26%; balloon 38%) was significantly correlated to an attenuated PAI-1 increase after 24 h in the ticlopidine group (P = 0.007; restenosis, relative Delta PAI-1 + 50 +/- 28%; non-restenosis, + 139 +/- 50%), but not in the coumadin group. In the balloon-only group late restenosis (ISR) was associated with a trend for an augmented PAI-1 increase after 24 h. CONCLUSIONS: Coronary stent implantation significantly increases t-PA and PAI-1 plasma levels up to 1 week compared with balloon angioplasty alone. ISR in ticlopidine-treated patients was associated with an attenuated early PAI-1 active antigen increase. A less than 50% increase 24 h after stent implantation under ticlopidine treatment may identify patients at risk for the development of ISR.

Aged↗

Mitochondrial genotype and risk for Alzheimer's disease: cross-sectional data from the Vienna-Transdanube-Aging "VITA" study.

The Vienna Transdanube Aging (VITA) study searches for early markers of Alzheimer's disease (AD) by examining the mental status in a community-based cohort of 606, 75-years old volunteers that are then related to various clinical and genetic analyses. To determine whether mutations in mtDNA are involved in expression of AD, the mtDNA of 79 "control" participants is screened for alterations by sequencing of "hot-spot-regions". This study on mtDNA mutations has eliminated the influence of aging on the occurrence of mtDNA alterations by sequencing samples from persons at the age of exactly 75 years. Thus, our cohort reveals a snap-shot of mitochondrial sequences of elderly persons. So far, a high percentage (56%) of persons with known or unknown mutations in the fragments analyzed were found. These data will be compared in due time to a cohort of participants with proven late-onset AD.

Aged↗

[Effect of high frequency application on the tongue base. In vitro results of "radiofrequency application" on the porcine tongue base].

BACKGROUND AND OBJECTIVE: A newly developed radio-frequency monopolar needle electrode was evaluated in vitro on porcine tongues. PATIENTS AND METHODS: Porcine tongues with different tissue temperatures (20+/-1) degrees C and (32+/-2) degrees C were coagulated for 90 s. In a second step, 23 coagulations at 7 W were applied (34+/-2) degrees C. RESULTS: The volume of the lesion correlated well with increasing temperature. In step two, the mean energy was 238 J and the mean volume of the lesion was 507 mm(3) (100+/-15)%. Prolonged energy application did not correlate with a larger volume of the lesion. CONCLUSION: The new radio-frequency needle electrode can reduce tongue volume in a precise and controlled manner (SD+/-15%).

Animals↗

Human transportation influences Aedes aegypti gene flow in Southeast Asia.

Estimates of population genetic organization and gene flow of Aedes aegypti, the main vector of dengue viruses, have provided insights into dengue epidemiology. To assess the role of the vector in the changing pattern of dengue in Southeast Asia, extensive studies on the genetic differentiation of Aedes aegypti have been carried out. Among them, vector differentiation has been estimated for Cambodia, Thailand and South Vietnam using microsatellite markers. Analysis showed that there was less genetic differentiation between mosquito populations from Ho Chi Minh City and Phnom Penh than from either of them and Thailand, suggesting that passive migrations through human transportation help to explain this pattern of differentiation.

Aedes↗

[Principals of high frequency surgery].

Electrosurgical instruments are routinely and daily applied at a variety of indications in Otorhinolaryngology. They can be used for cutting, coagulation and devitalisation. All have in common that the high frequency energy is transported into the tissue via an instrument and by this causes a thermal change. Depending on the duration and characteristic of the electricity a vaporisation of the tissue is effected through coagulation, devitalisation and carbonisation. The knowledge of the effects on the tissue by the choice of the different instrument parameters and application systems is essential for an ingenious therapeutically indication. In principal the following application methods for electrosurgery by modulation of the high frequency parameters are distinguished: the monopolar and the bipolar coagulation and devitalisation and the monopolar and the bipolar cutting. This article deals with the physical basis, the effects in the tissue as well as the single application methods of the high frequency surgery.

Electrocoagulation↗

Comparison of colour Doppler imaging and retinal scanning laser fluorescein angiography in healthy volunteers and normal pressure glaucoma patients.

PURPOSE: To correlate retinal circulatory measurements using scanning laser fluorescein angiography and flow velocities of retrobulbar vessels measured by means of colour Doppler imaging. METHODS: Fifteen patients with normal pressure glaucoma (NPG) and 15 healthy volunteers underwent colour Doppler imaging and fluorescein angiographic studies. Peak systolic velocities (PSVs), end-diastolic velocities (EDVs) and resistive indices (RIs) of the ophthalmic artery (OA) and central retinal artery were obtained. In the fluorescein angiograms arteriovenous passage time (AVP) was quantified by means of digital dye dilution curve analysis. RESULTS: Arteriovenous passage time was significantly prolonged in NPG patients compared to healthy subjects (p = 0.0026). In the central retinal artery PSV (p = 0.023) and EDV (p < 0.0001) were significantly decreased and RI was increased (p < 0.0001) in patients with NPG. The EDV of the central retinal artery showed a significant correlation with AVP (EDV: r = - 0.53, p = 0.0023). The RI of the central retinal artery correlated significantly to AVP (RI: r = 0.63, p < 0.0001). The AVP did not correlate to EDV or PSV, nor to the RI measured in the ophthalmic artery. CONCLUSION: Arteriovenous passage time, which represents blood flow in a vascular segment of artery, capillary bed and corresponding vein, was found to be correlated to the EDV and the RI of the central retinal artery. The combination of different techniques allows further interpretation of ocular circulatory responses.

Adult↗

c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice.

The search for signalling systems regulating development of noradrenergic and cholinergic sympathetic neurons is a classical problem of developmental neuroscience. While an essential role of bone morphogenetic proteins for induction of noradrenergic properties is firmly established, factors involved in the development of cholinergic traits in vivo are still enigmatic. Previous studies have shown that the c-ret receptor and cholinergic properties are coexpressed in chick sympathetic neurons. Using in situ hybridization we show now that a loss-of-function mutation of the c-ret receptor in mice dramatically reduces numbers of cells positive for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) in stellate ganglia of homozygous newborn animals. The number of neurons positive for tyrosine hydroxylase (TH) mRNA, the rate-limiting enzyme of noradrenaline synthesis, is reduced to a smaller degree and expression levels are not detectably altered. Already at embryonic day 16 (E16), ChAT and VAChT-positive cells are affected by the c-ret mutation. At E14, however, ChAT and VAChT mRNAs are detectable at low levels and no difference is observed between wildtype and mutant mice. Our data suggest that c-ret signalling is necessary for the maturation of cholinergic sympathetic neurons but dispensable for de novo induction of ChAT and VAChT expression.

Acetylcholine↗

The role of environment in shaping the genetic diversity of the subalpine mosquito, Aedes rusticus (Diptera, Culicidae).

The relative involvement of larval dietary tolerance to the leaf-litter toxic polyphenols in shaping population genetic structure of the subalpine mosquito Aedes rusticus was examined. This was compared with other parameters such as geographical range, type of vegetation surrounding the breeding site, and occurrence of annual larvicidal treatments. Population genetic structure was analysed at 10 presumed neutral polymorphic isoenzyme loci. Toxicological comparisons involved standard bioassays performed on larvae fed on toxic decomposed leaf litter. Significant overall genetic differentiation was observed among the 22 studied populations and within the five defined geographical groups. Analysis of molecular variance revealed an absence of relation between genetic and environmental parameters, genetic variance being essentially found within populations. This suggested that the larval dietary tolerance to the toxic leaf litter and the other studied parameters poorly influence population genetic structure. The local adaptation of subalpine mosquito populations to the surrounding vegetation thus appears as a labile trait. Such a dynamic adaptation is also suggested by the correlation between geographical and toxicological distances and the correlation between dietary tolerance to the leaf-litter toxic polyphenols and annual larvicidal treatments.

Aedes↗

Vienna Transdanube Aging "VITA": study design, recruitment strategies and level of participation.

The Vienna Transdanube Aging study "VITA" is a prospective, interdisciplinary cohort-study of all 75-years old inhabitants of the 21. and 22. district of Vienna (n = 1,745), which started in May 2000. The study design is described in this paper for the first time. The main scientific question of the study concerns the prediction of incident dementia in the elderly. The main statistical analysis will compare 8 predictors: episodic memory, verbal fluency, subjective memory complaints, depression, APOE-epsilon4, MAO-B activity in thrombocytes, MRT hippocampal atrophy, and MRT atrophy of the substantia innominata. The whole investigation comprises medical and psychosocial interviews, psychological tests, psychiatric and neurological scales, blood characteristic, genetic factors and cranial magnetic resonance imaging. Various variables will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. The dependent variable of the intended statistical analysis will be the individual's difference between Mini Mental State Examination scores at the two times of investigation. A high level of participation in geriatric epidemiological studies increases the general applicability of results but recruitment procedures must not ignore the individual's right to privacy and integrity. Using a liberal recruitment procedure as recommended by the local ethics commission the level of participation is between 36.7% and 44.3%.

Aged↗

Temporal genetic variation in Aedes aegypti populations in Ho Chi Minh City (Vietnam).

Aedes aegypti, the main vector of dengue viruses in Asia, displays variation in population density over time. The larval habitats of this species being unevenly distributed and transient (depending on cycles of drought and flood), the forces generating temporal variation in gene frequencies in populations are studied. We sampled seven mosquito populations from Ho Chi Minh City (Vietnam) and its suburbs on five occasions between April 1999 and August 2000. We investigated genetic variation by studying isoenzyme and microsatellite polymorphism and susceptibility to a dengue 2 virus strain. Ae. aegypti populations collected during the dry season (January-April) showed genetic differentiation (F(ST) = 0.016, P < 10(-6) for isoenzymes) and showed more differentiated infection rates of the dengue 2 virus. The genetic structure of the population is less marked during the rainy season (F(ST) = 0.081, P < 10(-6)). Thus, environmental factors, such as rainfall and factors related to human activity, such as breeding site density and insecticide treatment, control the genetic structure of Ae. aegypti populations in the short term. The implications of studies of this kind for the design of future control programmes are discussed.

Aedes↗

Genetic differentiation of the dengue vector, Aedes aegypti (Ho Chi Minh City, Vietnam) using microsatellite markers.

Dengue haemorrhagic fever emerged in the 1950s and has become a major public health concern in most Asian countries. In Vietnam, little is known about the intraspecific variation of the vector and its consequences on vectorial capacity. Here we report the use of microsatellite markers to differentiate Aedes aegypti populations in Ho Chi Minh City, a typical, overcrowded Asian city. Six microsatellite loci, with 5-14 alleles per locus, were scored in 20 mosquito samples collected in 1998 in Ho Chi Minh City. We found substantial differentiation among Ae. aegypti populations from the outskirts, whereas populations from the centre of the city showed less differentiation. These results are consistent with the hypothesis that populations of Ae. aegypti in central Ho Chi Minh City are panmictic because there are abundant larval breeding sites and an abundance of humans for adults to feed upon. In contrast, populations on the outskirts become differentiated largely through the processes of genetic drift because larval breeding sites are not as abundant. These findings implicate human activities associated with urbanization, as factors shaping the genetic structure of Ae. aegypti populations.

Aedes↗

Glycine activates myenteric neurones in adult guinea-pigs.

1. We studied the effects of glycine on myenteric neurones and muscle activity in the colon and stomach of adult guinea-pigs. 2. Intracellular recordings revealed that myenteric neurones responded to local microejection of glycine (1 mM) with a fast, transient membrane potential depolarisation (57 % of 191 colonic neurones and 26 % of 50 gastric neurones). Most glycine-sensitive neurones had ascending projections and were choline acetyltransferase immunoreactive. Glycine preferentially activated neurones with a late afterhyperpolarisation (AH-neurones) and tonic spiking neurones with fast synaptic inputs (tonic S-neurones) but less frequently phasic S-neurones and inexcitable (non-spiking) neurones. The depolarisation had a reversal potential at -19 +/- 13 mV, which was increased by 18 +/- 10 % upon lowering extracellular chloride concentration and decreased by 38 +/- 14 % in furosemide (frusemide, 2 mM). 3. Strychnine (300 nM) reversibly abolished the glycine-induced depolarisation and the Cl(-) channel blocker picrotoxin (100 microM) reduced the amplitude of the depolarisation by 55 +/- 5 %. The glycine effect was a postsynaptic response because it was not changed after nerve blockade with tetrodotoxin (1 microM) or blockade of synaptic transmission in reduced extracellular [Ca(2+)]. The effect was specific since the response was not changed by the nicotinic antagonists hexamethonium (200 microM) and mecamylamine (100 microM), the GABA(A) receptor antagonist bicuculline (10 microM), the NMDA antagonist MK-801 (20 microM) or the 5-HT(3) antagonist ICS 205930 (1 microM). 4. Glycine (1 mM) induced a tetrodotoxin- and strychnine-sensitive contractile response in the colon; the contractile response in the stomach was tetrodotoxin insensitive. 5. Glycine activated myenteric neurones in the adult enteric nervous system through strychnine-sensitive mechanisms. The glycine-evoked depolarisation was caused by Cl(-) efflux and the maintenance of relatively high intracellular chloride concentrations involved furosemide-sensitive cation-chloride co-transporters.

Animals↗