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Biomedical subjects

I Lang

Publications and source records attributed to I Lang.

At least 19 recordsLinked to original sources
PubMed2006

The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study.

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, many patients develop a severe progressive small vessel pulmonary arteriopathy that is inaccessible to surgical intervention and is associated with poor survival. The purpose of the present study was to evaluate the medium-term efficacy and safety of the dual endothelin receptor antagonist, bosentan, in inoperable CTEPH. Forty-seven patients with inoperable CTEPH (distal disease or persistent pulmonary hypertension following PEA) underwent evaluation after 1 yr of bosentan therapy. Outcomes included assessment of 6-min walk test (6MWT), haemodynamics and World Health Organization functional classification. Monitoring of serious adverse effects and changes in therapy was undertaken. Patients showed sustained improvements in 6MWT (49+/-8 m), functional classification, cardiac index (+0.2+/-0.07 L.min(-1).m(-2)) and total pulmonary resistance (-139+/-42 dyn.s.cm(-5)). Those patients with persisting pulmonary hypertension following PEA showed the greatest improvement. One-yr survival was 96%, and bosentan was well tolerated with only one patient developing deranged liver function. Although all patients with chronic thromboembolic pulmonary hypertension should be considered for pulmonary endarterectomy, bosentan provides an alternative medical therapy to improve function and delay the progression of this devastating disease in those in whom surgery is not suitable.

Adult↗
PubMed2006

Initial experiences with novel therapy for pulmonary hypertension in Slovakia.

Pulmonary hypertension (PH) is the most serious and potentially devastating chronic disorder of the pulmonary circulation with diverse etiologies and pathogenesis characterized by abnormal increased vasoconstriction and vascular remodelling. Current specific therapy of PH is based on an understanding of its pathogenesis and is acting through pathogenic pathways and therefore changes therapeutic strategy, effectively improves clinical course and prolongs life. The authors discuss the actual classification, pathogenesis in short and particularly actual treatment modalities and the impact on the natural history of this disorder. In chronic thromboembolic pulmonary hypertension is pulmonary endarterectomy if correct indicated the curable method, warranted substantial improvement of life quality and survival. These novel therapies of PH were absent in Slovakia until recently. The authors present initial experiences, results of PH management up to date on the basis of cooperation with PH centres in Austria and Czech Republic (Tab. 1, Fig. 6, Ref. 32).

Adult↗
PubMed2005

Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy.

AIMS/HYPOTHESIS: The human placenta is a complex organ situated at the interface between mother and foetus that separates maternal from foetal blood. The placental surfaces exposed to the two bloodstreams are different, i.e. trophoblasts and endothelial cells are in contact with the maternal and foetal circulation, respectively. Both cell types produce high insulin receptor levels. The aim of the present study was to test the hypothesis that spatio-temporal changes in insulin receptor expression in trophoblasts from first trimester to the endothelium at term shift the control of insulin-dependent processes from mother to foetus. METHODS: Global microarray analysis of primary trophoblasts from first trimester and term human placentas and endothelial cells from term human placentas cultured under hyperinsulinaemic and control conditions identified different sets of regulated genes in trophoblasts and endothelial cells. RESULTS: Insulin effects on placental gene expression underwent developmental changes from trophoblasts in the first trimester to endothelial cells at term that were paralleled by changes in levels of activated insulin receptors. The changes in gene regulation were both quantitative (i.e. magnitude of effect) and qualitative (i.e. specific genes affected and direction of regulation). CONCLUSIONS/INTERPRETATION: This spatio-temporal shift in insulin sensitivity throughout pregnancy allows maternal and foetal insulin to regulate different processes within the placenta at different gestational stages, facilitated by compartmentalisation of the insulin response. Thus, by altering the levels and function of insulin receptors in space and time, control of insulin-dependent processes in the human placenta will change from mother to foetus throughout gestation. This will be of particular interest in conditions associated with altered maternal or foetal insulin levels, i.e. diabetes mellitus or intrauterine growth restriction.

Blood Circulation↗
PubMed2005

Endocytosis and vesicle trafficking during tip growth of root hairs.

The directional elongation of root hairs, "tip growth", depends on the coordinated and highly regulated trafficking of vesicles which fill the tip cytoplasm and are active in secretion of cell wall material. So far, little is known about the dynamics of endocytosis in living root hairs. We analyzed the motile behaviour of vesicles in the apical region of living root hairs of Arabidopsis thaliana and of Triticum aestivum by live cell microscopy. For direct observation of endocytosis and of the fate of endocytic vesicles, we used the fluorescent endocytosis marker dyes FM 1-43 and FM 4-64. Rapid endocytosis was detected mainly in the tip, where it caused a bright fluorescence of the apical cytoplasm. The internalized membranes proceeded through highly dynamic putative early endosomes in the clear zone to larger endosomal compartments in the subapical region that are excluded from the clear zone. The internalized cargo ended up in the dynamic vacuole by fusion of large endosomal compartments with the tonoplast. Before export to these lytic compartments, putative early endosomes remained in the apical zone, where they most probably recycled to the plasma membrane and back into the cytoplasm for more than 30 min. Endoplasmic reticulum was not involved in trafficking pathways of endosomes. Actin cytoskeleton was needed for the endocytosis itself, as well as for further membrane trafficking. The actin-depolymerizing drug latrunculin B modified the dynamic properties of vesicles and endosomes; they became immobilized and aggregated in the tip. Treatment with brefeldin A inhibited membrane trafficking and caused the disappearance of FM-containing vesicles and putative early endosomes from the clear zone; labelled structures accumulated in motile brefeldin A-induced compartments. These large endocytic compartments redispersed upon removal of the drug. Our results hence prove that endocytosis occurs in growing root hairs. We show the localization of endocytosis in the tip and indicate specific endomembrane compartments and their recycling.

Arabidopsis↗
PubMed2004

Membrane-wall attachments in plasmolysed plant cells.

Field emission scanning electron microscopy of plasmolysed Tradescantia virginiana leaf epidermal cells gave novel insights into the three-dimensional architecture of Hechtian strands, Hechtian reticulum, and the inner surface of the cell wall without the need for extraction. At high magnification, we observed fibres that pin the plasma membrane to the cell wall after plasmolysis. Treatment with cellulase caused these connecting fibres to be lost and the pinned out plasma membrane of the Hechtian reticulum to disintegrate into vesicles with diameters of 100-250 nm. This suggests that the fibres may be cellulose. After 4 h of plasmolysis, a fibrous meshwork that labelled with anti-callose antibodies was observed within the space between the plasmolysed protoplast and the cell wall by field emission scanning electron microscopy. Interestingly, macerase-pectinase treatment resulted in the loss of this meshwork, suggesting that it was stabilised by pectins. We suggest that cellulose microfibrils extending from strands of the Hechtian reticulum and entwining into the cell wall matrix act as anchors for the plasma membrane as it moves away from the wall during plasmolysis.

Cell Membrane↗
PubMed2004

Porphyrin metabolism in lymphocytes of miners exposed to diesel exhaust at oil shale mine.

The present study was carried out on the evaluation and application of new biomarkers for populations exposed to occupational diesel exhaust at oil shale mines. Since not only genotoxic effects may play an important role in the generation of tumors, the level of porphyrin metabolism was proposed as a biomarker of diesel exhaust exposure effects. The data on determination of 5-aminolevulinic acid (ALA) synthesis and heme formation in lymphocytes from groups of 50 miners exposed to diesel exhaust and 50 unexposed surface workers of oil shale mine are presented. All workers were examined and interviewed using structured questionnaires. The levels of benzene, carbon monoxide and nitric oxides in air as well as concentrations of 1-nitropyrene and elemental carbon in particulate matter were used for evaluation of exposure to diesel exhaust in mine. The levels of ALA and protoporphyrin (PP), activities of ALA synthetase (ALA-S) and ferrochelatase (FC), as well as levels of PP associated with DNA (PP/DNA) were investigated in lymphocytes spectrophotometrically. Significant differences in activity of ALA synthesis and heme formation between exposed miners and surface workers were found (207+/-23 vs. 166+/-14 pmol/10(6) lymp./30' for ALA-S and 46.1+/-3.8 vs. 54.8+/-4.1 pmol/10(6) lymp./60' for FC activities, respectively, P<0.001). ALA-S activity was higher and ALA accumulated in lymphocytes of exposed miners. Inhibition of FC activity caused PP cellular accumulation and an increase in the PP/DNA level (P<0.05). Tobacco smoking led to the increase of ALA biosynthesis in lymphocytes of both surface and underground smokers. The comparison of data obtained for non-smokers and smokers of both groups of workers has shown a significant difference (P<0.05). The work duration of underground or surface workers did not significantly influence the investigated biochemical parameters. The determination of ALA synthesis in lymphocytes could be a useful biomonitoring index of organism sensitivity to underground working. The alterations of PP levels, FC activity and PP/DNA association in peripheral lymphocytes of miners illustrate the harmful effects of exposure to diesel exhaust.

Adult↗
PubMed2004

[Influence of various occupational factors on building workers].

The authors obtained data demonstrating that peculiarities of each building object, wide variety of building operations at various stages of construction and constantly renewed technologies and construction materials complicate unequivocal evaluation of work conditions in building industry and require a system of occupational monitoring for health state among all construction industry occupations, in accordance with work conditions and length of service.

Adult↗
PubMed2003

Percutaneous interventions in radiation-associated coronary in-stent restenosis.

This study was performed to evaluate the outcome of percutaneous revascularization in "edge restenoses" developing after radioactive stent implantation in de novo and in-stent lesions. Twenty-one consecutive patients undergoing target lesion revascularization (TLR) at any follow-up after phosphorus-32 radioactive stent implantation were included in this study. We assessed the incidence of death, myocardial infarction, repeated TLR and recurrent angina over the following 18 months. After 6 months, TLR rate was 28.6%, and no stent thromboses, deaths or Q-wave myocardial infarctions occurred. Among the patients with TLR there were significantly more subjects who had received a radioactive stent in a previous in-stent restenosis (66.7% vs. 0% in patients without second restenosis; P <0.001), or who had received two radioactive stents (83.3% vs. 33.3%; P = 0.038). After 18 months, TLR rate was 33.3%, and two patients (9.5%) had died. Restenosis after intravascular radiotherapy can be safely treated by percutaneous interventional techniques, yielding an acceptable clinical result within 18 months.

Adult↗
PubMed2003

Saliva secretion and ionic composition of saliva in the cockroach Periplaneta americana after serotonin and dopamine stimulation, and effects of ouabain and bumetamide.

Isolated salivary glands of Periplaneta americana were used to measure secretion rates and, by quantitative capillary electrophoresis, Na(+), K(+), and Cl(-) concentrations in saliva collected during dopamine (1 micro M) and serotonin (1 micro M) stimulation in the absence and presence of ouabain (100 micro M) or bumetanide (10 micro M). Dopamine stimulated secretion of a NaCl-rich hyposmotic saliva containing (mM): Na(+) 95 +/- 2; K(+) 38 +/- 1; Cl(-) 145 +/- 3. Saliva collected during serotonin stimulation had a similar composition. Bumetanide decreased secretion rates induced by dopamine and serotonin; secreted saliva had lower Na(+), K(+) and Cl(-) concentrations and osmolarity. Ouabain caused increased secretion rates on a serotonin background. Saliva secreted during dopamine but not serotonin stimulation in the presence of ouabain had lower K(+) and higher Na(+) and Cl(-) concentrations, and was isosmotic. We concluded: The Na(+)-K(+)-2Cl(-) cotransporter is of cardinal importance for electrolyte and fluid secretion. The Na(+)/K(+)-ATPase contributes to apical Na(+) outward transport and Na(+) and K(+) cycling across the basolateral membrane in acinar P-cells. The salivary ducts modify the primary saliva by Na(+) reabsorption and K(+) secretion, whereby Na(+) reabsorption is energized by the basolateral Na(+)/K(+)-ATPase which imports also some of the K(+) needed for apical K(+) extrusion.

Animals↗
PubMed2001

Identification of a novel exon in apolipoprotein E receptor 2 leading to alternatively spliced mRNAs found in cells of the vascular wall but not in neuronal tissue.

Novel members of the low density lipoprotein receptor family were identified in human endothelial and vascular smooth muscle cells utilizing a homology-cloning strategy. Four novel mRNA transcripts could be identified as isoforms of the apolipoprotein E receptor 2 (apoEr2): one form lacking three ligand binding repeats (nucleotides 497-883) but containing a novel ligand binding repeat adjacent to a unique cysteine-rich domain preceding the epidermal growth factor precursor domain of apoEr2, forms lacking the O-linked sugar domain, and forms containing a 59-amino acid deletion within the cytoplasmic tail. By fluorescence in situ hybridization for chromosome mapping, we could confirm that the novel alternative forms of apoEr2 are splice variants of transcripts from a single copy gene on chromosome 1p34. To analyze whether the different splice variants of apoEr2 mRNA are expressed in a splice variant-specific pattern, we concentrated on the central nervous system, where high expression of apoEr2 has been described originally. By means of splice variant-specific in situ hybridization, we could confirm that apoEr2 mRNA is abundantly expressed in brain tissue and, with exception of the newly identified ligand binding domain, all mRNA splice variants exhibited a similar expression pattern. The mRNA of the newly identified ligand binding domain, however, was expressed in brain only in cells of the vascular wall, confirming data from Northern blotting, where the mRNA of the newly identified ligand binding domain was found in several tissues but was absent in brain tissue.

Alternative Splicing↗
PubMed2001

Dopamine-induced epithelial K(+) and Na(+) movements in the salivary ducts of Periplaneta americana.

K(+)- and Na(+)-selective double-barrelled microelectrodes were used for intracellular and luminal measurements in salivary ducts of Periplaneta americana. The salivary ducts were stimulated with dopamine (10(-6) mol l(-1)). Dopamine decreased intracellular [K(+)] from 112+/-17 mmol l(-1) to 40+/-13 mmol l(-1) (n=6) and increased intracellular [Na(+)] from 22+/-19 mmol l(-1) to 92+/-4 mmol l(-1) (n=6). Luminal [K(+)] was 15+/-3 mmol l(-1) in the unstimulated salivary ducts and increased to 26+/-11 mmol l(-1) upon stimulation with dopamine (n=10). Luminal [Na(+)] was insignificantly increased from 105+/-25 mmol l(-1) to 116+/-22 mmol l(-1) (n=12) by stimulation with dopamine. The potential difference across the basolateral membrane (PD(b)) was depolarized from -65+/-6 mV to -31+/-13 mV (n=12) and the transepithelial potential difference (PD(t)) was hyperpolarized from -13+/-6 mV to -22+/-7 mV (n=22, lumen negative) upon stimulation with dopamine. The re-establishment of prestimulus values of intracellular [K(+)] and [Na(+)] and PD(b) was inhibited by basolateral addition of ouabain (10(-4) mol l(-1)). Furosemide (10(-4) mol l(-1)) in the bath inhibited the dopamine-induced increase in intracellular [Na(+)], the decrease in intracellular [K(+)] and the depolarization of PD(b). We propose a model for dopamine-stimulated ion transport in the salivary ducts involving basolateral Na(+)-K(+)-2Cl(-) cotransport and active extrusion of K(+) via the apical membrane.

Journal Article↗
PubMed2001

Differential mitogenic responses of human macrovascular and microvascular endothelial cells to cytokines underline their phenotypic heterogeneity.

A variety of growth factors promote the complex multistep process of angiogenesis. The mitogenic activity of vascular endothelial growth factors (VEGFs) and placental growth factors (PlGFs), known as cytokines acting predominantly on endothelial cells, was tested on human umbilical vein endothelial cells (HUVEC) and microvascular endothelial cells (MIEC) and compared with the potency of the universally acting basic fibroblast growth factor (FGF-2). The cells were seeded at different cell numbers and incubated with various doses of growth factors for a period of 24-72 h in culture medium +/- serum. Proliferation was determined by measuring the optical density after staining the cells with the tetrazolium salt WST-1. VEGF121 and VEGF165 increased the number of HUVEC and MIEC at low and high seeding densities various doses and incubation times. The efficiency of FGF-2 was less pronounced at high seeding densities of the cells under serum-free conditions. PlGF-1 and PlGF-2 stimulated mitogenesis on HUVEC only at low cell numbers and after a short incubation time by 125 +/- 3% and 102 +/- 5% (P < 0.001), respectively. Longer incubation times with the lower seeding density in the absence of FCS did not induce a significant stimulatory effect of the PlGFs. MIEC responded stronger to all growth factors. In particular under serum free conditions, PlGF-1 and PlGF-2 effectively stimulated cell proliferation by 247 +/- 54% (P < 0.01) and 288 +/- 40% (P < 0.05) at low cell numbers, and by 81 +/- 13% (P < 0.05) and 49 +/- 13% (P < 0.01), respectively, at high cell numbers. The addition of fetal calf serum caused a reduced proliferative response of all growth factors on both cell types related to the controls. In conclusion, MIEC and HUVEC differ in their proliferative response to VEGFs, PlGFs and FGF-2.

Capillaries↗
PubMed2001

Self-expanding metal esophageal stent with anti-reflux mechanism.

BACKGROUND: When deployed across the gastroesophageal junction, self-expanding metal esophageal stents can predispose to gastroesophageal reflux. Our aim was to evaluate the efficacy of a self-expanding metal esophageal stent that was modified to prevent gastroesophageal reflux. METHODS: The polyurethane coating of a metal Z-stent was extended beyond its lower end to form windsock-type valve. The anti-reflux property of this stent was studied in vitro by submerging the stent under water and measuring the pressure required to invert the valve. Esophageal acid exposure time was measured in 5 dogs with a standard and the modified stent placed across the gastroesophageal junction. The modified stent was also placed in 11 patients with cancer of the gastroesophageal junction who were prospectively followed. RESULTS: The pressure required to invert the valve was directly proportional to the thickness of the valve membrane (48 +/- 0.4 cm water for a 0.0067-inch thick membrane). Esophageal acid exposure time was significantly less with the modified stent as compared with a standard stent (1% +/- 0.3%, 49% +/- 11%, respectively, p = 0.03). Dysphagia score in patients improved from 3.4 +/- 0.1 to 1.1 +/- 0.2 (p < 0.001). Daytime heartburn and regurgitation scores were less than 1 (score 10 = severe). No patient complained of nocturnal reflux symptoms. Karnofsky performance status scale did not improve significantly. CONCLUSIONS: The efficacy of the modified stent in relieving dysphagia is comparable with a standard stent. It also effectively prevents gastroesophageal reflux.

Aged↗