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M Dabrowski

Publications and source records attributed to M Dabrowski.

At least 19 recordsLinked to original sources
PubMed2005

Chorionic mRNA expression and N-glycodiversity of pregnancy-associated glycoprotein family (PAG) of the European bison (Bison bonasus).

Placental PAG mRNA expression and N-glycodiversity of multiple PAG proteins secreted in vitro by trophectoderm (chorion epithelium) of wild pecoran Bovidae taxons was not examined previously. The study on European bison (Eb) aimed: (1) to determine placental PAG mRNA expression by in situ hybridisation; (2) to identify a profile of pecoran PAG protein family secreted in vitro by cotyledonary (CT) explants; (3) to examine N-glycodiversity of the PAG proteins in this wild taxon. In addition, we compared (4) a profile and N-glycodiversity of the PAG protein family secreted in vitro by CT and interCT-trophectoderm (intCT-TRD) explants of domestic ruminants. Cotyledonary sections of the Eb were used for in situ hybridisation (ISH) with (35)S-labelled probes produced with porcine PAG cDNA as templates. Various CT and intCT-TRD explants were long-term cultured in vitro. Chorionic proteins were isolated from media, ultra-filtrated (>10 kDa MWCO) and analysed by PAGE-Western blotting with various polyclonal anti-PAG sera. Protein samples with or without enzymatic deglycosylation were examined after different times of explant cultures. Released chorionic proteins were deglycosylated by N-glycanase F (PNGase F+) and compared to glycosylated forms (PNGase F-). This is the first paper demonstrating the PAG-like mRNA transcript expression (by ISH) and N-glycodiversity of immuno-reactive PAG-like proteins (produced in vitro by chorionic explants) of European bison. Various PAG proteins of Eb (EbPAG) were secreted by CT explants during long-term in vitro studies. Major approximately 78, approximately 67 and approximately 65 kDa EbPAG-like proteins were reduced by enzymatic deglycosylation (at least by 10 kDa). Considerably smaller amounts of approximately 45 kDa EbPAG-like proteins were also observed. In addition, we have found that various PAG proteins (30-73 kDa) were secreted by bovine CT explants, during long-term in vitro cultures. Corresponding amounts of PAG proteins, similar in M(r), were also secreted by intCT-TRD explants, whose tissues were not utilised for PAG protein extraction during other scientists' previous studies. It seems that the M(r)-heterogeneity and N-glycodiversity of the PAG protein family can play very important role during feto-placental interactions in Bovidae species.

Animals↗
PubMed2003

Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues.

AIMS/HYPOTHESIS: We investigated the pharmacological properties of two novel ATP sensitive potassium (K(ATP)) channel openers, 6-Chloro-3-isopropylamino-4 H-thieno[3,2- e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) and 6-chloro-3-(1-methylcyclopropyl)amino-4 H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414), on the cloned cardiac (Kir6.2/SUR2A), smooth muscle (Kir6.2/SUR2B) and pancreatic beta cell (Kir6.2/SUR1) types of K(ATP) channel. METHODS: We studied the effects of these compounds on whole-cell currents through cloned K(ATP) channels expressed in Xenopus oocytes or mammalian cells (HEK293). We also used inside-out macropatches excised from Xenopus oocytes. RESULTS: In HEK 293 cells, NNC 55-0118 and NN414 activated Kir6.2/SUR1 currents with EC(50) values of 0.33 micromol/l and 0.45 micromol/l, respectively, compared with that of 31 micro mol/l for diazoxide. Neither compound activated Kir6.2/SUR2A or Kir6.2/SUR2B channels expressed in oocytes, nor did they activate Kir6.2 expressed in the absence of SUR. Current activation was dependent on the presence of intracellular MgATP, but was not supported by MgADP. CONCLUSION/INTERPRETATION: Both NNC 55-0118 and NN414 selectively stimulate the pancreatic beta-cell type of K(ATP) channel with a higher potency than diazoxide, by interaction with the SUR1 subunit. The high selectivity and efficacy of the compounds could prove useful for treatment of disease states where inhibition of insulin secretion is beneficial.

ATP-Binding Cassette Transporters↗
PubMed2003

Characterisation of new KATP-channel mutations associated with congenital hyperinsulinism in the Finnish population.

AIMS/HYPOTHESIS: ATP-sensitive potassium (K(ATP)) channels are crucial for the regulation of insulin secretion from pancreatic beta cells and mutations in either the Kir6.2 or SUR1 subunit of this channel can cause congenital hyperinsulinism (CHI). The aim of this study was to analyse the functional consequences of four CHI mutations (A1457T, V1550D and L1551V in SUR1, and K67N in Kir6.2) recently identified in the Finnish population. METHODS: Wild type or mutant Kir6.2 and SUR1 subunits were coexpressed in Xenopus oocytes. The functional properties of the channels were examined by measuring currents in intact oocytes or giant inside-out membrane patches. Surface expression was measured by enzyme-linked immunosorbance assay, using HA-epitope-tagged subunits. RESULTS: Two mutations (A1457T and V1550D) prevented trafficking of the channel to the plasma membrane. The L1551V mutation reduced surface expression 40-fold, and caused loss of MgADP and diazoxide activation. Both these factors will contribute to the lack of K(ATP) current activation observed in response to metabolic inhibition in intact oocytes. The L1551V mutation also increased the channel open probability, thereby producing a reduction in ATP-sensitivity (from 10 micro mol/l to 120 micro mol/l). The fourth mutation (K67N mutation in Kir6.2) did not affect surface expression nor alter the properties of K(ATP) channels in excised patches, but resulted in a reduced K(ATP) current amplitude in intact cells on metabolic inhibition, through an unidentified mechanism. CONCLUSION/INTERPRETATION: The four CHI mutations disrupted K(ATP) channel activity by different mechanisms. Our results are discussed in relation to the CHI phenotype observed in patients with these mutations.

ATP-Binding Cassette Transporters↗
PubMed2003

Acute and 3-month treatment effects of candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure.

BACKGROUND: This study evaluated the short-term and long-term effects of the angiotensin II type 1 receptor antagonist candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure (CHF). METHODS: In this multicenter, double-blind, parallel-group study, 218 patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction < or =40%) and pulmonary capillary wedge pressure > or =13 mm Hg were randomly assigned to 12 weeks of treatment with placebo (n = 44) or candesartan cilexetil (2 mg [n = 45], 4 mg [n = 46], 8 mg [n = 39], or 16 mg [n = 44]) once daily after a 2-week placebo run-in period. Hemodynamic measurements were performed by right heart catheterization over a 24-hour period after single (day 1) and repeated (3-month) treatment with the study drug. RESULTS: On regression analysis of the time-response curves, single and multiple doses of candesartan cilexetil produced sustained, significant, and dose-dependent reductions in pulmonary capillary wedge pressure (short-term effect P =.036, long-term effect P =.035) and mean pulmonary arterial pressure (short-term effect P =.031, long-term effect P =.042). Systemic vascular resistance showed a trend toward decreasing with dose on short-term and long-term treatments. No consistent changes were seen in cardiac index. Compensatory increases in plasma renin activity and angiotensin II levels with decreases in aldosterone and atrial natriuretic peptide were dose-dependent and significant. Candesartan cilexetil improved clinical symptoms, stabilized patient New York Heart Association status compared with placebo, and was judged to be an efficacious treatment by the investigators. More patients receiving placebo stopped the trial prematurely because of an adverse event than in any candesartan cilexetil group, and there was no excess of deaths in any treatment group. Candesartan was safe and well tolerated at all dosages. CONCLUSIONS: Candesartan cilexetil demonstrated significant short-term and long-term improvements in hemodynamic, neurohormonal, and symptomatic status and was well tolerated in patients with CHF.

Adolescent↗
PubMed2001

Effect of repaglinide on cloned beta cell, cardiac and smooth muscle types of ATP-sensitive potassium channels.

AIMS/HYPOTHESIS: The carbamoylbenzoic acid derivative repaglinide is a potent short-acting insulin secretagogue that acts by closing ATP-sensitive potassium (KATP) channels in the plasma membrane of the pancreatic beta cell. In this paper we investigated. the specificity of repaglinide for three types of cloned (KATP) channel composed of the inwardly rectifying potassium channel Kir6.2 and either the sulphonylurea receptor SUR1, SUR2A or SUR2B, corresponding to the beta cell, cardiac and either smooth muscle types of KATP channel, respectively. METHODS: The action of the drug was studied by whole-cell current recordings of KATP channels expressed either in Xenopus oocytes or mammalian cells (HEK293). We also used inside-out macropatches excised from Xenopus oocytes for detailed analysis of repaglinide action. RESULTS: The drug blocked all three types of KATP channel with similar potency, by interacting with a low-affinity site on the pore-forming subunit of the channel (Kir6.2: half-maximal inhibition 230 micromol/l) and with a high-affinity site on the regulatory subunit, the sulphonylurea receptor (SUR: half-maximal inhibition 2-8 nmol/l). There was no difference in potency between channels containing SUR1, SUR2A or SUR2B. MgADP potentiated the inhibitory effect of repaglinide on Kir6.2/SUR1 and (to a lesser extent) Kir6.2/SUR2B, but not on Kir6.2/SUR2A. CONCLUSION/INTERPRETATION: Repaglinide interacts with a site common to all three types of sulphonylurea receptor leading to inhibition of the KATP channel. The fact that MgADP potentiated this effect in the case of the beta cell, but not cardiac, type of channel could help explain why the drug shows no adverse cardiovascular side-effects in vivo.

ATP-Binding Cassette Transporters↗
PubMed2000

[Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease].

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.

Adult↗
PubMed1999

Light and electron microscopic picture of atherosclerotic plaque in stable and unstable angina.

By presenting this series of 127 cases of coronary atherectomy the authors join the workers who study morphological differences between the atherosclerotic plaques in stable and unstable angina. Routine staining of formalin-fixed, paraffin-embedded material was completed by the detection of T lymphocytes, macrophages, mast cells, smooth myocytes and grown-in capillaries using monoclonal antibodies (DAKO), as well as by the immunofluorescent demonstration of fibrinogen in the plaques. The plaques derived from patients with unstable angina showed a higher incidence of mast cells (significant) and macrophages (insignificant). These cells render the plaque more susceptible to rupture or fissuring. There was also significantly more frequent and quantitatively more abundant permeation of the plaque by fibrinogen that raises the chance of thrombosis. These findings support the view that unstable angina correlates with the phenomena that favour the rupture of the plaque and thrombosis. Electron microscopy has not been used so far to study coronary atherosclerotic plaques. This material includes 15 plaques from stable and 18 plaques from unstable angina. A cover of fibrin and blood platelets is a regular formation on the surface and in the superficial layer of the plaque from unstable angina. It contributes to the "thrombotic proneness" of the coronary artery. These plaques also show abundant elastic fibres. This pattern corresponds to myo-elastic intimal hyperplasia ("intimal thickening") where the production of intimal elastin constitutes an essential phenomenon. Intimal thickening is interpreted as a preatherosclerotic event. The presence of elastin reflects an early stage of the development of the plaque. The plaque from stable angina shows abundant collagen fibres, which aggravate the lesion.

Adult↗
PubMed1998

Protection patterns of tRNAs do not change during ribosomal translocation.

The translocation reaction of two tRNAs on the ribosome during elongation of the nascent peptide chain is one of the most puzzling reactions of protein biosynthesis. We show here that the ribosomal contact patterns of the two tRNAs at A and P sites, although strikingly different from each other, hardly change during the translocation reaction to the P and E sites, respectively. The results imply that the ribosomal micro-environment of the tRNAs remains the same before and after translocation and thus suggest that a movable ribosomal domain exists that tightly binds two tRNAs and carries them together with the mRNA during the translocation reaction from the A-P region to the P-E region. These findings lead to a new explanation for the translocation reaction.

Binding Sites↗
PubMed1998

Differential RNA display identifies novel genes associated with decreased vitamin D receptor expression.

To characterize further the function of the intracellular vitamin D receptor (VDR), we have developed stable transfectant variants of a vitamin D-responsive cell line (U937) which express either decreased or increased numbers of VDR. In this study we have analyzed changes in gene expression associated with this variable VDR expression. Initial experiments indicated that a 50% decrease in VDR levels was associated with a 2-fold increase in cell proliferation and a similar rise in c-myc mRNA expression. Further studies were carried out using differential RNA display (DD). Sequence analysis of DD products revealed two cDNAs with identity to known gene products: the catalytic sub-unit of DNA-protein kinase (DNA-PK(CS)), and the peroxisomal enzyme 17beta-hydroxysteroid dehydrogenase type IV (17beta-HSD IV). Northern analysis confirmed that expression of both mRNAs was reduced in cells with decreased numbers of VDR. Down-regulation of 17beta-HSD IV mRNA expression was associated with enhanced estradiol inactivation by U937 cells, suggesting a link between estrogenic pathways and cell proliferation. Further Northern analyses indicated that there was no significant change in 17beta-HSD IV or DNA-PK(CS) mRNA levels following treatment with 1,25(OH)2D3, although expression of both genes varied with changes in cell proliferation. These data suggest that, in addition to its established role as a hormone-dependent trans-activator, VDR may influence gene expression by ligand-independent mechanisms.

17-Hydroxysteroid Dehydrogenases↗
PubMed1998

High-Pressure Bail-out Coronary Stenting Without Anticoagulation: Early Outcome and Follow-up Results.

PURPOSE:The purpose of this study is to assess the immediate outcome and long-term results of high pressure bail-out coronary stenting without subsequent anticoagulation. PATIENTS AND METHODS: Between June 1994 and September 1996, 32 consecutive patients (males 24, mean age 55 +/- 9.3 years) underwent bail-out stenting at a mean deployment pressure of 15.5 +/- 2.3 mmHg because of complicated PTCA. A total of 54 stents (Palmaz-Schatz, Micro, Gianturco Roubin and Wiktor) were implanted, from one to four stents into each vessel. After the procedure all patients were treated with ticlopidine 500 mg/day and acetylosalicylic acid 300 mg/day only. RESULTS: Stents were successfully delivered in all patients. In the cath lab procedural success was 96.9%. During the in-hospital phase, there was one (3.1%) acute stent thrombosis followed by urgent bypass surgery (CABG). Four (12.5%) non-Q wave myocardial infarctions occurred. There were no subacute stent thrombosis or hemorrhagic complications. Six month angiographic restudy in 28 patients showed restenosis in 13 (46.4%): 9 patients were treated successfully by rePTCA. At one year 13 (40.6%) major adverse cardiac events occurred: eleven (34.4%) target lesion revascularizations (9 PTCA, 2 CABG), one (3.1%) elective CABG surgery and one (3.1%) late cardiac death. Event-free survival was 93.8% at one month, 65.6% at six months, and 59.4% at one year. CONCLUSIONS: High pressure bail-out coronary stenting with antiplatelet regimen is an effective and safe procedure for treating complicated PTCA. Although the restenosis rate is high, in most cases in-stent restenosis can be treated by rePTCA. In 60% of patients clinical course at one year was uneventful.

Journal Article↗
PubMed1997

A novel class of RanGTP binding proteins.

The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. Although Ran has been implicated also in a variety of other processes, such as cell cycle progression, a direct function of Ran has so far only been demonstrated for importin-mediated nuclear import. We have now identified an entire class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. We have confirmed specific RanGTP binding for some of them, namely for two novel factors, RanBP7 and RanBP8, for CAS, Pse1p, and Msn5p, and for the cell cycle regulator Cse1p from Saccharomyces cerevisiae. We have studied RanBP7 in more detail. Similar to importin-beta, it prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP. RanBP7 binds directly to nuclear pore complexes where it competes for binding sites with importin-beta, transportin, and apparently also with the mediators of mRNA and U snRNA export. Furthermore, we provide evidence for a Ran-dependent transport cycle of RanBP7 and demonstrate that RanBP7 can cross the nuclear envelope rapidly and in both directions. On the basis of these results, we propose that RanBP7 might represent a nuclear transport factor that carries an as yet unknown cargo, which could apply as well for this entire class of related RanGTP-binding proteins.

Amino Acid Sequence↗
PubMed1997

[Liver abscess in the course of ulcerative colitis].

The case of 19 year old female patient treated because of the ulcerative colitis. The abscess of the liver has appeared in this patient. This kind of complication has been never described in medical literature.

Adult↗
PubMed1997

Kainate-evoked modulation of gene expression in rat brain.

Kainate is a glutamate analog that produces neuronal excitation resulting in seizures within hours following its intraperitoneal injection into adult rats. Then, at 2-3 days after the treatment, neurodegeneration of apoptotic character can be observed in limbic system. As a consequence, plastic reorganization and glial reactivation phenomena occur. These physiological and pathological responses are reflected by specific changes in gene expression, that can be dissected according to their spatio-temporal patterns. The early phase of gene expression observed in all hippocampal subfields appears to reflect a sudden burst of spiking activity. Changes in mRNA levels restricted to dentate gyrus are suggestive of a link to neuronal plasticity. The late gene expression response implies its correlation either to neuronal cell death or glial reactivation, depending on cellular localization of gene products. Thus analysis of the temporal and spatial gene expression pattern in the hippocampus after kainate treatment may provide clues revealing specific phenomena to which gene expression could be attributed.

Animals↗
PubMed1996

Antisense inhibition of vitamin D receptor expression induces apoptosis in monoblastoid U937 cells.

The active vitamin D3 metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3) acts as an antiproliferative and differentiating agent for the monoblastoid cell line U937 and as an important immunologic mediator implicated particularly in the function of cells belonging to the monocyte/macrophage lineage. These effects are controlled by the vitamin D receptor (VDR), a member of the steroid hormone receptor family. The objective of this study was to develop U937 transfectants expressing antisense VDR mRNA, and to use these to examine the role of 1,25(OH)2D3-VDR interaction in this lineage. A 2-kb VDR cDNA insert (including the complete VDR coding region) was cloned in an antisense orientation into the EBV episomal vector pMEP4 under the control of an inducible promoter and transfected into U937. The resultant cell line, DH42, was hygromycin resistant, contained VDR cDNA, expressed fewer VDRs than controls, and showed a substantial decrease in antiproliferative response to 1,25(OH)2D3. However, 1,25(OH)2D3 increased the number of cells expressing macrophage cell surface Ags, including CD14 and CD11b. A subpopulation of smaller cells did not express the differentiation markers after cadmium stimulation. Cell cycle analysis showed shifts in the distribution of cells from G1 to S phase, which were more pronounced after cadmium treatment. A considerable proportion of cells were outside the cycle and DNA fragmentation confirmed apoptosis. Thus, the functional outcome of the VDR antisense transfection suggests that in the myelomonocytic lineage, VDR expression may act as a protective mechanism against programmed cell death.

Actins↗
PubMed1996

[Early and long-term outcome after coronary artery patency].

The role of percutaneous transluminal coronary angioplasty (PTCA) in the management of chronically occluded coronary arteries is still controversial. Percutaneous transluminal coronary angioplasty of chronic total occlusion is associated with relatively low success rates and a high incidence of restenosis. The purpose of this analysis was to determine, from the records of our institution, the efficacy and long-term outcome of angioplasty performed for chronic total occlusion defined as complete occlusion (Thrombolysis in Myocardial Infraction [TIMI] grade 0). PTCA was performed in 212 consecutive patients with chronically occluded coronary arteries and was successful in 125 (59%) patients. Complications were not observed. Successful initial PTCA was related to the clinical duration of occlusion and the type of guidewire (the primary success rate with the conventional guidewire was 49 (48%) versus 76 (69.1%) with Magnum Meier System p < 0.01). Repeat angiography was performed for 65 (52.0%) consecutive patients with successful initial PTCA and demonstrated restenosis in 34 (52.3%). 17 patients were successfully treated by a second PTCA. Restenosis or reocclusion was not clearly related to the residual stenosis post PTCA. In addition, the grade of collateral supply was not different in the vessels with and without restenosis.

Adult↗