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E Michalak

Publications and source records attributed to E Michalak.

At least 19 recordsLinked to original sources
PubMed2006

Generation of transgenic rabbits by the novel technique of chimeric somatic cell cloning.

A novel technique of chimeric somatic cell cloning was applied to produce a transgenic rabbit (NT20). Karyoplasts of transgenic adult skin fibroblasts with Tg(Wap-GH1) gene construct as a marker were microsurgically transferred into one, previously enucleated, blastomere of 2-cell non-transgenic embryos, while the second one remained intact. The reconstructed embryos either were cultured in vitro up to the blastocyst stage (Experiment I) or were transferred into recipient-females immediately after the cloning procedure (Experiment II). In Experiment I, 25/102 (24.5%) embryos formed blastocysts from whole embryos and 46/102 (44.12%) embryos developed to the blastocyst stage from single non-operated blastomeres, while the reconstructed blastomeres were damaged and degenerated. Thirteen (12.7%) embryos did not exceed 3- to 4-cell stages and 18 (17.7%) embryos were inhibited at the initial 2-cell stage. Out of 14 blastocysts which were subjected to molecular analysis, the transgene was detected in the cells of 4 blastocysts. In Experiment II, 163/217 (75.0%) embryos were transferred into 9 pseudopregnant recipient-rabbits (an average of 18 embryos per recipient). Four recipient-females (44.4%) became pregnant and delivered a total of 24 (14.7%) pups. Molecular analysis confirmed that two pups (1.2%), one live and one stillborn, showed a positive transgene signal. Live transgenic rabbit NT20 appeared healthy and anatomically as well as physiologically normal. The results of our experiments showed that transgenic adult skin fibroblast cell nuclei, which have been introduced into the cytoplasmic microenvironment of single enucleated blastomeres from 2-cell stage rabbit embryos, are able to direct the development of chimeric embryos not only to the blastocyst stage but also up to term.

Animals↗
PubMed2006

Ischemic epigenetics and the transplanted kidney.

The primary purpose of this investigation was to study oxidative demethylation of DNA following ischemia/reperfusion injury (I/RI) that putatively influences posttransplant gene expression in transplanted kidneys. Our hypothesis was that as a result of I/RI, oxidative damage, which is inherent in solid organ transplantation, may lead to aberrant demethylation of cytosine-guanine (CpG) sites within gene promoter regions of DNA. The methylated CpG sites normally contribute to the binding of proteins that render DNA inaccessible to transcription factors. Therefore, conversion of methylated cytosines to nonmethylated cytosines by oxidative damage in postischemic organs might facilitate enhanced gene expression in donor organs by exposing the demethylated CpG site in a gene promoter to DNA-binding proteins that enhance gene transcription. In this study, we investigated the demethylation of a specific CpG within the IFNgamma response element resident in the promoter region of the C3 gene in the rat kidney. In response to 24 hours of cold ischemia and a subsequent 2 hours of reperfusion in an isolated ex-vivo circuit, we observed a significant change in the ratio of methylated to unmethylated cytosines at this site. Epigenetic modifications to donor DNA have not been previously investigated, but our own data suggests that they have the potential to modify gene expression posttransplantation. Since epigenetic modification may become stable and heritable upon mitosis, such changes to the donor organ DNA may persist with enormous implications for transplant outcomes.

Animals↗
PubMed2004

Stroke volume and systolic time intervals: beat-to-beat comparison between echocardiography and ambulatory impedance cardiography in supine and tilted positions.

The aim of the study was to compare stroke volume (SV), ejection time (ET) and pre-ejection period (PEP) measurements obtained using a central haemodynamics ambulatory monitoring device based on impedance cardiography (ICG), in supine and tilted positions (60 degrees), with pulsed Doppler echocardiography as a non-invasive reference method. The Holter-type ICG device was used for off-line, beat-to-beat, automatic determination of SV, ET and PEP. ICG data were compared with those obtained simultaneously using pulsed Doppler echocardiography in the ascending aorta from a suprasternal projection, 1 min before and 10 min after tilting. The tests were performed in 13 young, healthy subjects (six men and seven women, aged 23-33 years). Linear regression between the measured values obtained for all subjects was described by the following formulas: SVicg= 13.9 + 0.813 x SVecho (r = 0.857, SEE = 9.03, n = 496), ETicg = 16.8 + 0.987 x ETecho (r = 0.841, SEE=21.3, n = 496), PEPicg= 22.8 + 0.890 x PEPecho (r = 0.727, SEE = 14.6, n = 496). The data showed that ambulatory impedance cardiography gives useful absolute values of SV and systolic time intervals measured in supine and tilted positions.

Adult↗
PubMed1996

Increased frequency of organ-specific cardiac antibodies in healthy relatives of patients with dilated cardiomyopathy: evidence for autoimmunity in Polish families.

BACKGROUND AND HYPOTHESIS: Autoantibodies represent markers of autoimmune involvement and are found with increased frequency in patients and their symptom-free relatives at risk compared with normal controls. Cardiac-specific autoantibodies, detected by immunofluorescence, were found in 20% of symptom-free relative of patients with dilated cardiomyopathy (DCM) from England and Italy. The role of autoimmunity may vary in DCM patients from Poland due to ethnic differences in genetic susceptibility to autoimmune disease. METHODS: We assessed the frequency of the organ-specific cardiac autoantibodies in 162 symptom-free relatives of DCM patients [85 male, mean (SD) age 27 (18) years] and 80 control subjects from Poland. Familial DCM (> 1 affected member) was present in 4 families, nonfamilial DCM in the remaining 24 pedigrees. We performed antibody screening and noninvasive cardiological assessment in the whole group. RESULTS: The frequency of cardiac-specific autoantibodies was higher among patients with documented DCM (probands and relatives) (50%) and their symptom-free relatives (38%) than in unrelated normal subjects (10%; p = 0.0001). In 24 (86%) of the pedigrees studied, autoantibodies were found in the proband and/or in at least one family member and tended to be more common in familial than in nonfamilial DCM (50 vs. 35%, p = NS). Echocardiographic indices of left ventricular size and function were similar in relatives with and without detectable antibodies. CONCLUSIONS: The presence of cardiac-specific autoantibodies in symptom-free relatives of DCM patients provides evidence for autoimmunity in the majority (86%) of our pedigrees, including both familial and nonfamilial forms of DCM.

Adolescent↗
PubMed1996

Determinants of prognosis in nonischemic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy, a heart muscle disease of unknown cause, is characterized by high mortality and is a major cause of cardiac transplantation. It has become, therefore, increasingly important to identify patients at higher risk. The aim of this study was to assess which of the data obtained at the time of diagnosis are the best predictors of survival. METHODS AND RESULTS: One hundred forty-four patients with dilated cardiomyopathy (118 men; mean age, 39 years) were assessed clinically, noninvasively, and hemodynamically. The effect of variables derived from the evaluation on outcome (death or heart transplantation) was examined. During a mean follow-up time of 4.1 years, 68 patients (47%) died and 9 (6%) underwent heart transplantation. The 1-, 2-, and 5-year transplant-free survival rate was 79, 69, and 44%, respectively. Cox multivariate regression analysis identified three variables as independent predictors of outcome: (1) pulmonary artery systolic pressure, P = .0001; (2) left ventricular ejection fraction, P = .0013; and (3) left ventricular end-diastolic dimension, P = .007. The prognostic index was constructed from regression coefficients and parameters significant in the Cox model. The minimal prognostic index in the study group was 1.4 and the maximal was 6.0 with a corresponding 1-year survival of 98 and 18%, respectively. The validity of the prognostic index was tested in the consecutive group of 81 patients, who were followed for a mean 2.3 years. The prognostic index of the poor outcome group differed significantly from that in survivors (3.7 vs 2.9, respectively, P < .01). The sensitivity and specificity of model predictions were 68 and 52%, respectively. CONCLUSIONS: The severity of pulmonary hypertension and left ventricular dysfunction provides an independent insight into the prognosis of patients with dilated cardiomyopathy. The prognostic index is useful when assessing prognosis and may be helpful in the timing of heart transplantation.

Adult↗
PubMed1995

The standard electrocardiogram as a screening test for hypertrophic cardiomyopathy.

Phenotypic heterogeneity in hypertrophic cardiomyopathy (HC) makes definitive diagnosis difficult, particularly during family screening. We studied the electrocardiogram (ECG) as a potential initial screening test in patients with HC. Using accepted diagnostic criteria, we examined the ECGs and echocardiograms of 159 patients with a confirmed clinical or genetic diagnosis of HC. An abnormal ECG was found in 154 patients (97%) while only 146 (92%) showed an abnormal echocardiogram. Of the former, 9 patients (6%) had normal echocardiograms and had been diagnosed on the basis of identification of a mutation in the beta myosin heavy chain gene (n = 8) or obligate carrier status (n = 1). Only 1 of these 9 patients was under age 20, the time at which hypertrophy is normally expressed on the echocardiogram. The remaining 5 patients (3%) without ECG abnormality consisted of 1 patient with an echocardiogram clearly diagnostic of HC and 4 clinically normal patients (aged 13, 24, 29, and 33 years) with normal echocardiograms who had been diagnosed by mutation identification (n = 3) or obligate carrier status (n = 1). Thus only these latter 4 patients (3%) would not have been diagnosed as having HC based on an abnormal ECG and/or abnormal echocardiogram. Screening relatives for HC by ECG criteria alone detects all those whom an echocardiogram will diagnose. While echocardiography aids in the specificity of HC diagnosis, the ECG, within the context of a family with a proven case of HC, is a more sensitive marker of the disease. It is therefore both a cost-effective and useful tool for screening those to proceed to echocardiography.

Adolescent↗
PubMed1995

Left ventricular enlargement is common in relatives of patients with dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy is characterized by dilation and impaired contractility of one or both ventricles. Long-term prognosis is poor. Early diagnosis has the potential for substantial reduction of morbidity and mortality. Recent studies, based on echocardiographic assessment of relatives of the patients have shown that familial dilated cardiomyopathy is relatively common. The authors studied 215 relatives (mean age, 27 years; 111 male) of 38 index patients with idiopathic dilated cardiomyopathy by clinical examination, electrocardiography, and two-dimensional, M-mode and Doppler echocardiography. Seven relatives (3%) from six families were shown to have dilated cardiomyopathy. Thus, 6 of the 38 index patients (16%) had familial disease. Furthermore, left ventricular enlargement either during diastole or systole was found in 66 of 174 healthy relatives (38%). This is significantly more frequent than in our normal control population of 100 unrelated subjects studied in the same way (18%; P < .0001). These 66 relatives with left ventricular enlargement belonged to 27 of the 38 examined families (71%). Dilated cardiomyopathy was found to be familial in 16% of patients. Of the relatives examined, 41% had left ventricular abnormalities. These findings provide further evidence for a genetic background of dilated cardiomyopathy. Relatives with left ventricular enlargement may have an early stage and/or latent form of the disease.

Adult↗
PubMed1995

Organ-specific cardiac autoantibodies in dilated cardiomyopathy. Frequency and clinical correlates in Polish patients.

Organ- and disease-specific cardiac autoantibodies are found in a third of dilated cardiomyopathy patients from the U.K. and Italy and represent markers of autoimmune involvement. The role of autoimmunity may vary in dilated cardiomyopathy patients from different countries due to differences in genetic susceptibility to autoimmune diseases. The aim of this study was to assess the frequency of organ-specific cardiac autoantibodies detected by immunofluorescence in a consecutive series of patients with dilated cardiomyopathy and in disease and normal control subjects from Poland. The study groups included 79 patients with idiopathic (WHO criteria) dilated cardiomyopathy, 55 patients with other cardiac disease and 60 normal subjects. Cardiac antibody tests were performed by indirect immunofluorescence on human heart; skeletal muscle was used to identify cross-reacting antibodies. The frequency of organ-specific cardiac autoantibodies was higher in patients with dilated cardiomyopathy (21/79, 27%) than in controls with other cardiac disease (1/55, 2% P < 0.001) or in normal subjects (7/60, 12% P < 0.02). Conversely, cross-reactive antibodies were detected in similar proportions in patients with dilated cardiomyopathy (5/79, 6%), disease controls (7/55, 13%) and normal subjects (6/60, 10%, P = ns). The organ-specific antibody was more common in patients with dilated cardiomyopathy with insidious onset of disease (17/34, 50%) compared to those who did not exhibit this feature (4/45, 9%, P < 0.0001). Organ- and disease-specific cardiac autoantibodies were found in 27% of Polish patients with dilated cardiomyopathy at diagnosis; this is evidence for autoimmune involvement in a subset of patients from our country, as seen in a previously reported series of Western European origin. The association of antibody status with insidious onset of symptoms is in keeping with the long latency period observed in other autoimmune disorders.

Adult↗
PubMed1994

Concentration of RGDS-containing degradation products in uremic plasma is correlated with progression in renal failure.

A concentration of protein degradation products containing the RGDS sequence, which could contribute to a lower reactivity of uremic platelets, has been estimated in both uremic (n = 16) and control (n = 7) plasmas. Degradation products and other small molecules were separated from plasma by filtration through AMICON YM-10 filter. RGDS antigen was determined in filtered material using the radioimmunoassay method based on monospecific anti-RGDS rabbit polyclonal antibodies. The concentration of RGDS-containing degradation products in uremic plasma ranged from 0.8 to 353 nM with mean value 58.6 +/- 24.9 nM and was higher than in control (0.7 to 5.9 nM, mean value 2.1 +/- 0.9 nM). Moreover, the level of RGDS-antigen positively correlated with plasma creatinine concentration (R = 0.87, p < 0.001). The filtered material showed an inhibitory effect on fibrinogen binding to control platelets in respect to RGDS-antigen concentration. We conclude that the elevated concentration of RGDS-containing degradation products in uremic plasma is partially responsible for bleeding tendency in renal failure.

Adult↗
PubMed1994

The electrocardiogram is a more sensitive indicator than echocardiography of hypertrophic cardiomyopathy in families with a mutation in the MYH7 gene.

BACKGROUND: Mutations in the cardiac beta myosin heavy chain gene causing hypertrophic cardiomyopathy have been identified, and to assist both diagnosis and prediction of outcome attempts have been made to correlate phenotype and genotype. Two new mutations in codon 403 of the gene in three unrelated families are described and attention drawn to variable or even absent phenotypic expression in different family members. METHODS AND RESULTS: The polymerase chain reaction and heteroduplex analysis on Mutation Detection Enhancement gels were used to search for mutations in the globular head of the beta myosin heavy chain gene in families with hypertrophic cardiomyopathy. Two mutations were found in exon 13 (codon 403) of the gene. In two unrelated Polish families the mutation resulted in the conversion of arginine to tryptophan (CGG: >TGG). A second mutation, found in a British family, converted the same arginine to leucine (CGG: >CTG). These mutations were detected in family members who had electrocardiographic and echocardiographic features typical of hypertrophic cardiomyopathy; however, they were also detected in 7 other adult relatives with an abnormal electrocardiogram but a normal echocardiogram. Two unrelated adult relatives had completely normal clinical findings but carried the gene mutation. CONCLUSIONS: Identification of a specific mutation gives no guide to the clinical phenotype. There is considerable variability in the phenotypic expression of hypertrophic cardiomyopathy. Mutations were detected in adults previously regarded as normal or in whom the diagnosis was questionable. The fact that the clinical significance of the mutation in these people is still unknown emphasises the dilemma facing screening programmes. Isolated, unexplained electrocardiographic abnormalities in first degree relatives in a family with a definitive diagnosis of hypertrophic cardiomyopathy should be regarded as evidence of a carrier state.

Adult↗
PubMed1994

Expression of fibrinogen receptors on platelets of uremic patients is correlated with the content of GPIIb and plasma level of creatinine.

Platelets of uremic patients, activated with ADP, exposed less fibrinogen receptors than control platelets, i.e. 24612 +/- 5541 and 33400 +/- 4302 receptors per platelet, respectively. However, this difference was not statistically significant. When compared with the total number of GPIIb/IIIa complexes, quantified from platelet glycoprotein IIb (GPIIb) contents, active receptors on the platelet surface represented 13.6% and 35.1% of total pool of fibrinogen receptors in uremic and control platelets, respectively. The number of exposed fibrinogen receptors was positively correlated with the amount of GPIIb copies in both uremic and normal platelets. In uremic platelets, both the number of exposed receptors and the number of GPIIb copies were correlated with the plasma creatinine concentration suggesting, that binding of fibrinogen to uremic platelets depends upon the degree of renal failure. Uremic platelets contain similar amounts of fibrinogen as control ones i.e. 13.2 +/- 2.3 micrograms and 17.6 +/- 2.2 micrograms per 1 x 10(8) platelets, respectively. Whereas for beta-thromboglobulin (beta-TG) there was a significant difference of 392 +/- 102 ng and 803 +/- 202 ng per 1 x 10(8) platelets, respectively. Reduced beta-TG content in uremic platelets suggests limited platelet activation in vivo. These results support the concept that uremic platelets have impaired functions and indicate that there is a relationship between the progression in renal failure and disability of platelets in thrombosis.

Adenosine Diphosphate↗
PubMed1993

[Left ventricular hypertrophy and blood pressure values during 24-hour ambulatory monitoring and office measurements in essential hypertension].

119 hypertensive patients were examined by 24-hour ambulatory blood pressure monitoring (ABPM) and traditional (casual) blood pressure measurements. The echocardiographic examination was also performed. Mean and maximal systolic and diastolic blood pressure values, systolic and diastolic pressure amplitude as well as traditional blood pressure values were correlated with left ventricular walls thickness and left ventricular mass. Maximal values were obtained for left ventricular mass and mean systolic blood pressure (especially in the evening). No statistically significant correlation was stated for left ventricular mass and systolic pressure amplitude. The correlation coefficients of left ventricular mass and wall thickness with ABPM were significantly higher than those calculated from echocardiographic parameters and traditional blood pressure measurements.

Adult↗
PubMed1991

The decreased circulating platelet mass and its relation to bleeding time in chronic renal failure.

The mean platelet volume, measured optically and by the electrical impedance method, was analysed in the patients with chronic renal failure. All parameters describing the circulating platelet biomass except the platelet volume heterogeneity were decreased in these patients. There is a strong inverse relation between the Ivy bleeding time and the platelet mass in the patient group. Our results indicate that the smaller platelets circulating in the patients with chronic renal failure may contribute to the uremic bleeding diathesis, and disturbed thrombocytopoiesis occurs in chronic renal failure.

Adult↗
PubMed1991

[Dilated cardiomyopathy in children and adolescents. Diagnostic problems, clinical course and prognosis].

UNLABELLED: The clinical profile of 19 patients with dilated cardiomyopathy from 2 to 18 years old (mean age 13.4 +/- 4 years) was reviewed to detect any factors that might be predictive for their survival. Follow-up study ranged from 5 to 105 months (mean 39 +/- 33 months). All patients received digitalis + diuretics, 12 were managed with immunosuppression, 16 with antiarrhythmics. There were 12 survivors and 7 nonsurvivors: the 1-year mortality was 21.2%, the 2-years mortality was 35.8%. All deaths were within first 2 years. In 12 patients who survived 2 years, significant improvement was noticed in 9 cases. Endomyocardial biopsy was performed in 16 patients. Four of them with histological diagnosis of myocarditis survived and in 3 of them a considerable improvement was noticed. Half of 12 patients with nonspecific histological findings died (p less than 0.05). There was no significant difference between survivors and nonsurvivors in all following parameters: the incidence of severe heart failure (NYHA class III-IV) and severe ventricular arrhythmias (Lown III-IV), relative heart volume, echocardiographic LVDD, haemodynamic parameters--CI, LVEF, LVEDP, LVEDVI. CONCLUSIONS: Clinical, electrocardiographic, echocardiographic and haemodynamic data are nonpredictive for survival. The most dangerous period are the first two years of illness. In long term, improvement was noticed in half of patients.

Adolescent↗
PubMed1991

[Atypical forms of hypertrophic cardiomyopathy].

UNLABELLED: Hypertrophic cardiomyopathy is characterized by a diverse clinical and morphological spectrum. In this report we describe five patients with atypical hypertrophic cardiomyopathy and significantly dilated atria. Diagnostic difficulties are stressed. All patients underwent clinical examination, noninvasive studies including 2-D echocardiogram, cardiac catheterization. In three patients endomyocardial biopsy was taken and examined by light microscopy. All but one patient were men, ranging in age from 28 years to 40 years at initial examination. In all patients disproportion between mildly elevated or, in two cases normal filling pressures and degree of dilatation of both atria was found. Two patients C.G. and D.T. had auscultatory and roentgenographic findings of mitral stenosis. Following echocardiographic and angiocardiographic studies an increase in left and right ventricular thickness associated with dilatation of both atria was found. Endomyocardial biopsy in both cases did not show endocardial thickening or infiltrative changes. In family S, two patients W.S. and Je.S had marginal left ventricular hypertrophy. The presence of left ventricular hypertrophy in patient Ja. S and finding, after family studies, hypertrophic, obstructive cardiomyopathy in patient A.S. enabled establishing the correct diagnosis. Beside varying degree of hypertrophy in family S, mild dilation of the right ventricle and incomplete right bundle branch block were found. In two patients of family S. restrictive cardiomyopathy was found, in patient Ja. S. during cardiac catheterization at initial presentation, in patient W.S. on doppler transmitral flow velocity examination at late follow-up. Paroxysmal atrial fibrillation was the first symptom in four patients, thromboembolic event in one patient. In four patients pacemaker requirement was found. During long-term follow-up (mean 4.8 years) slowly progressive heart failure associated with further dilatation of atria is observed. Mild doses of diuretics are effective in controlling congestive symptoms. CONCLUSION: in hypertrophic cardiomyopathy significantly dilated atria and clinical signs of mitral stenosis can be present. The presence of myocardial hypertrophy is not necessary to diagnose hypertrophic cardiomyopathy. Familial studies can be helpful in establishing the correct diagnosis.

Adolescent↗