Biomedical subjects

J Kunert

Publications and source records attributed to J Kunert.

At least 19 recordsLinked to original sources

PubMed2001

TGF beta-induced SMAD2 phosphorylation predicts inhibition of thymidine incorporation in CD34+ cells from healthy donors, but not from patients with AML after MDS.

Cells from patients with MDS-derived AML display heterogeneous proliferative responses to transforming growth factor beta (TGF beta). We analyzed growth inhibition and SMAD2 phosphorylation by TGF beta in CD34+ cells from nine patients, as compared to normal controls. While TGF beta consistently inhibited thymidine incorporation of normal cells (41% of control, P < 0.05), cells from patients with AML were growth-inhibited in only four of seven cases (40%), whereas TGF beta stimulated thymidine incorporation in the three other samples (166%). Remarkably, TPO reverted the stimulatory effect of TGF beta to profound growth inhibition. Upon exposure to TGF beta, SMAD2 protein was phosphorylated in normal CD34+ cells (n = 3), CD34+ leukemic blasts from all examined patients with AML (n = 4), and in the myeloid leukemic cell lines M-07e and HEL. TGF beta inhibited TPO-mediated thymidine incorporation, cell proliferation and survival in all samples analyzed. In M-07e cells and CD34+ cells from healthy donors, this inhibition was enhanced by an antagonist of JAK2 (AG490), but not a MEK-1 antagonist (PD098059). Conversely, in CD34+ cells from a patient with AML, both AG490 and PD098059 significantly enhanced TGF beta-mediated suppression of TPO-induced thymidine incorporation. Thus, in MDS-derived AML, altered responses to TGF beta may be due to defects downstream of SMAD2 and may involve MAPK activation.

Acute Disease↗

PubMed2001

Biopersistence of synthetic mineral fibers as a predictor of chronic inhalation toxicity in rats.

In December 1997 the European Commission (EC) adopted Directive 97/69/EC (O.J. L 343/19 of 13 December 1997) in which criteria were established for the classification and labeling of synthetic mineral fibers. This directive was derived based upon an extensive program evaluating current scientific knowledge on fiber pathogenicity and its relationship to the biopersistence of long fibers. Within this context, the biopersistence of fibers longer than 20 microm was found to be a good predictor of the lung burden and early pathological changes in chronic inhalation studies with fibers as well as of the tumor response in chronic intraperitoneal studies with fibers. The analysis that provided the scientific basis for the relationship of biopersistence to the chronic inhalation results is presented in detail. Proportional odds regression techniques were used to determine the relationship between both inhalation and intratracheal instillation biopersistence clearance half-times and the collagen deposition at the broncho-alveolar junction as determined following 24 mo in chronic inhalation toxicity studies. The results indicate all the indicators of biopersistence considered are equally good predictors of the early long-term change that occurs in the lung in response to more durable fibers. This change, the collagen deposition at the broncho-alveolar junction, is a precursor of interstitial fibrosis, which has been shown to be associated with tumor response in fiber-exposed animals. The results show that the clearance half-times set in the EC directive are within the baseline for this parameter.

Administration, Inhalation↗

PubMed2001

Biopersistence of synthetic mineral fibers as a predictor of chronic intraperitoneal injection tumor response in rats.

In December 1997 the European Commission (EC) adopted Directive 97/69/EC (O.J. L 343/19 of 13 December 1997), in which criteria were established for the classification and labeling of synthetic mineral fibers. This directive was derived based upon an extensive program evaluating current scientific knowledge on fiber pathogenicity and its relationship to the biopersistence of long fibers. Within this context, the biopersistence of fibers longer than 20 microm was found to be a good predictor of the lung burden and early pathological changes in chronic inhalation studies with fibers as well as of the tumor response in chronic intraperitoneal studies with fibers. The analysis that provided the scientific basis for the relationship of biopersistence to the chronic intraperitoneal (ip) results is presented in detail. Analysis of the relationship of biopersistence clearance half-times to ip tumor response shows a statistically significant relationship of ip tumor response to not only the number of fibers injected, but also the median length of the fibers injected and their solubility (clearance half-time). The results show that the biopersistence half-times as determined by intratracheal instillation (T(1/2) of WHO fibers or weighted T(1/2) of fibers with L > 20 microm) and as determined by inhalation (weighted T(1/2) of fibers with L > 20 microm) are equivalent predictors of the ip results. From these ip studies, fibers that can be exonerated from classification as carcinogens in Europe have a relative tumorigenic potency in the ip cavity of between 66 and 2500 times less than fibers that have been shown to produce a significant increase in tumors following chronic inhalation exposure. In addition, based upon the ip results, there is no statistical difference between the EC and the other fiber exoneration criteria, such as the German Gefahrstoffverordnung of 1999.

Animals↗

PubMed2001

Further studies on the multiple forms of protease ALP of Aspergillus fumigatus.

The author studied the presence of multiple forms of the main extracellular protease ALP in three strains of Aspergillus fumigatus that differed in geographical origin, and in mutants of one of these strains with disrupted genes coding for the main proteases ALP and MEP. The pattern of multiple proteolytic bands after isoelectric focusing was, in all three wild strains, nearly the same and was not changed after inactivation of the MEP gene. However, in ALP-deficient mutants all multiple forms also disappeared. The multiple forms observed must therefore be products of post-translational processing of the protease ALP and not true isoenzymes (products of different genes of a gene family). Further experiments did not prove that phosphorylation and glycosylation were involved in the formation of the multiple forms under study.

Aspergillus fumigatus↗

PubMed2000

Effect of peroxynitrite on dormant spores and germlings of Aspergillus fumigatus in vitro.

Peroxynitrite was tested for its effects on the opportunistic pathogenic fungus Aspergillus fumigatus. It did not kill any dormant or swollen (4 h in a glucose-peptone medium) conidia in concentrations up to 6.25 mmol/L and the growth of germlings (after 6 or 9 h) was only slightly inhibited by 5 mmol/L peroxynitrite. The peroxynitrite donor SIN-1 (up to 10 mmol/L, 1 d in buffer) did not kill any conidia but inhibited their germination and growth, depending on the medium. Ten mmol/L SIN-1 in a poor medium was fungistatic and germination was stopped for 20 h. Nine strains of A. fumigatus showed resistance comparable to the model strain, while 6 Candida albicans strains were much more susceptible to both peroxynitrite and its donor. The results indicate that peroxynitrite does not contribute substantially to the antifungal activity of phagocytes against A. fumigatus.

Animals↗

PubMed2000

Multiple forms of the serine protease Alp of Aspergillus fumigatus.

Alkaline proteases were produced by a virulent strain of Aspergillus fumigatus during growth on media containing glucose and proteins or peptides. After isoelectric focusing, six bands of proteolytic activity were detected with synthetic substrates after blotting on nitrocellulose membranes. The main protease (pI = 8.6) corresponded to the known subtilisin-like protease Alp of A. fumigatus and five minor components had lower isoelectric points (8.1 to 5.2). All proteases were produced on different media and in various phases of growth with only small quantitative variations. They also had identical pH optima, were denatured above 45 degrees C and stabilized by Ca2+ ions, were affected by the inhibitors of serine proteases only and had nearly identical substrate specificity against 13 synthetic substrates. On gel chromatography the three most acidic components had higher molecular weights than the main enzyme Alp. It remains to be determined if the enzymes under study arise through posttranslational processing of the main protease or are true isoenzymes, products of a gene family.

Animals↗

PubMed2000

Individual toluene exposure in rotary printing: increasing accuracy of estimation by linear models based on protocols of daily activity and other measures.

Industrial exposure varies distinctly both between persons and for each person over time. It is often not possible to measure individual exposure repeatedly due to high costs. Therefore, a method for assessment of exposure is needed that accounts for inter- and intraindividual variability. We consider a strategy suggested by Preller et al. (1995, Scandinavian Journal of Work, Environment, and Health 21, 504-512), the idea of which is to predict exposure on several days via a linear model using additional variables as regressors. Those additional variables are easier to obtain than exposure measurements and are assumed to influence exposure. The paper gives a theoretical proof of the use of this method. An example is given using toluene exposure data from a study in a rotogravure printing plant.

Biometry↗

PubMed1996

Acute blockage of the renin system and differential renal vein renin determinations in the diagnosis of renovascular hypertension.

For validation of differential renal vein renin determinations in the diagnosis of renovascular hypertension (RVH), we investigated 102 patients suspected of suffering from RVH before and 1 h after administration of 25 mg captopril. Sensitivity, specificity and posterior probability for renin ratio (RR) and renin secretion (RS) were calculated based on 44 patients with proven RVH and 58 patients with primary hypertension (PH) using discriminant analysis. There is good (> 95%) and identical specificity of both variables under all conditions, whereas sensitivity remains poor even after Captopril administration (RR 23% vs. 32%; RS 20% vs. 34%). The posterior probabilities obtained by discriminant analysis revealed a cut-off point of 2.5 for the renin ratio and of 1.9 for the renin secretion. No change is observed after ACE inhibition. We conclude that the acute blockade of the renin system by captopril in differential renin sampling yields no advantages in diagnosing RVH and that there is no difference between RR and RS in the diagnosis of RVH.

Adult↗

PubMed1995

Sexual behavior of natural family planning users in Germany and its changes over time.

For 10 years, a prospective study has been taking place in Germany to examine the use of natural family planning (NFP). As natural methods are behavioral methods, use-effectiveness, acceptability and continuation rates are very much influenced by patterns of sexual behavior. Therefore we performed an analysis of the sexual behavior of NFP users. Out of the data base of 1211 clients and 12,591 cycles we could identify a group of 300 women, all NFP beginners, with 5900 contraceptive cycles, who contributed at least 12 cycles with reliable recording of their sexual activity. Different groups were analyzed with methods of analysis of variance and regression models to find out significant differences in their sexual behavior with respect to sociodemographic structure and time of use. Nearly half of all the women systematically combine the fertility awareness part of NFP with other family planning methods. They use barriers in more than 60% of their cycles. The other half never or only in about 7% of their cycles use additional barrier methods. The latter show a clear decrease in barrier use in the course of time, whereas the frequent barrier users constantly combine the advantages of two family planning methods. Regarding the frequency of intercourse they are the sexually more active ones and show distinct sociodemographic characteristics. We could confirm the existence of three groups of NFP users, which differ significantly in their use of NFP as a family planning method. Despite these differences the low pregnancy rates indicate the conscious and risk-related sexual behavior of the group members.

Adult↗

PubMed1995

Effect of nitric oxide donors on survival of conidia, germination and growth of Aspergillus fumigatus in vitro.

The effect of nitric oxide (NO) donors on survival of conidia, germination and growth of the opportunistic pathogenic fungus Aspergillus fumigatus was investigated. Most efficient was sodium nitrite in an acidic milieu (pH 4.5). At a concentration of 5 mmol/L it killed all resting conidia in buffer within 16 h. S-Nitroso derivatives of thiols (cysteine, N-acetylcysteine and N-acetylpenicillamine) at the same concentration killed about 30-50% of spores within 24 h. The NO scavenger, oxyhemoglobin, abolished these effects. S-Nitrosoglutathione had no fungicidal effect and promoted germination. Sodium nitrite and S-nitroso-N-acetylcysteine inhibited germination of conidia in various media from concentration of 0.5 mmol/L and stopped it at concentrations of 1.4-2.9 mmol/L. In media with glucose and casein hydrolyzate or sodium nitrate as nitrogen source, growth inhibition by sodium nitrite (0.5-2 mmol/L) was only weak and mostly transient. In general, the used strain A. fumigatus seems to be less sensitive to nitric oxide donors than dimorphic pathogenic fungi. Thus, nitric oxide is probably not a major effector molecule in killing phagocytized elements of this fungus by host's immunocytes.

Animals↗

PubMed1994

Duplex sonography of the internal thoracic artery. Preoperative assessment.

Ultrasonic duplex scanning was used to examine 211 internal thoracic arteries. The investigating vessels were classified as normal, abnormal, and occluded. The results of the duplex examination were compared with angiography as the reference method. The diameter measurements showed virtually no differences between the two methods. Normal internal thoracic arteries showed a continuous decrease of the systolic flow velocities from proximal to distal and a narrow to moderate spectral flow curve, whereas arteries classified as abnormal showed a velocity profile distinct from that--in particular, no decrease of the systolic peak velocities and an increased spectral broadening during systole with peak frequencies greater than 4 kHz at 60 degrees (> 1.2 m/sec). In occluded vessels no flow could be detected. The majority of changes were found in the proximal part of the internal thoracic artery. All lesions were detected by duplex sonography. Six normal vessels were misjudged as abnormal by the duplex method. The sensitivity, specificity, and accuracy of duplex sonography compared with angiography as the reference method were 100% (95% CI, 74.4% to 100%), 96.9% (95% CI, 93.2% to 98.8%), and 97.2% (95% CI, 93.6% to 98.8%), respectively. Duplex sonography is a reliable, noninvasive technique for the preoperative assessment of the internal thoracic artery. It allows the detection of potential atherosclerotic changes in the internal thoracic artery and the assessment of adequacy of caliber and flow.

Adult↗

PubMed1993

Multicenter study of standardization of cell counting. Haemapheresis Scientific Workshop Group of DGTI.

Multicenter studies on cell separators give valid data (which can be compared between the different centers) only if the cell counting methods are uniform. This has to be demonstrated by ring studies or multicenter counting studies. Twelve apheresis centers involved in a multicenter study for the evaluation of the Fresenius AS 104 cell separator participated in such a ring study from July 1990 to July 1991. The twelve participating centers split into three significantly different groups according to the platelet counts in the platelet concentrates and a calculated pseudo extraction efficiency. No differences could be found in the white and red blood cell counts. No mailing effect--or time effect--and no personal effect could be found in the reference center.

Blood Component Removal↗

PubMed1993

Internal thoracic artery: prevalence of atherosclerotic changes.

Use of the internal thoracic artery for myocardial revascularization has regained general acceptance because it offers better long-term results than do venous conduits. The aim of this study was to ascertain the prevalence of atherosclerosis in the internal thoracic artery and to correlate the prevalence with other known risk factors. A total of 117 patients (male/female ratio 84:33; mean age 56.8 years) were investigated. Sixty-eight patients had coronary artery disease, 25 had combined coronary artery and valvular heart disease, 14 had acquired valvular heart disease, and 10 had other types of heart disease. All but one patient underwent bilateral semiselective internal thoracic arteriography. Evidence of atherosclerotic change was present in 6.6% of the opacified vessels in 11.1% of the investigated individuals. Although all patients with atherosclerotic lesions in the internal thoracic artery had coronary artery disease, no correlation could be found between coronary artery disease and internal thoracic atherosclerosis. Peripheral vascular disease and hyperlipidemia could be identified as predictors of atherosclerotic changes in the internal thoracic artery. Atherosclerosis is somewhat more prevalent in the internal thoracic artery in this study than in the literature. Although the internal thoracic artery is a protected vessel, there is a certain extent of atherosclerosis, that correlates with known risk factors. Our observations should not preclude use of the internal thoracic artery, but they should be considered for patients who are at risk for atherosclerotic changes of the internal thoracic artery.

Adult↗

PubMed1992

Genetics of dermatophytes.

By the end of 60s a team of scientists has started at Medical Faculty of Olomouc the research of micromycetes pathogenic for both the humans and animals. In this study, the appropriate results are summarized as concerned with the genetics of dermatophytes. Among these results, those significant in deeper assessing the biology of dermatophytes and etiopathogenesis of dermatophytoses have been selected. In our opinion, they may be of interest for the successors in the direction mentioned. Here are also formulated certain open problems and the applicative outputs are traced, for example, those concerning with vaccines. The approaches used, even unusual in the medical mycology from a traditional scope, are believed to prove the convenience of genetic methods when researching mycopathogens. We regret to miss at the edition of this publication the late founder of the team, RNDr. Nora Hejtmánková, CSc. which had the greatest contribution to the Chapters on the karyology and variability of dermatophytes as well as to the hybridization analysis of Trichophyton mentagrophytes complex.

Arthrodermataceae↗

PubMed1992

On the mechanism of penetration of ovicidal fungi through egg-shells of parasitic nematodes. Decomposition of chitinous and ascaroside layers.

The decomposition of egg-shells of Ascaris lumbricoides L. was studied microscopically using topochemical methods in a set of 32 strains of soil ovicidal fungi. It was found that even fungi displaying minimal chitinolytic activity in tests on purified chitin in vitro are able to dissolve chitin of egg-shells during the attack on live eggs. Fungi without any chitinolytic activity penetrate probably only the mechanically damaged eggs. None of the studied fungi was capable of degrading enzymatically the glycolipid (ascaroside) layer of the egg-shell which remained intact after digestion of all other components of the egg.

Animals↗

PubMed1991

[Has family planning behavior in West Germany changed since 1985?].

A survey on the family planning behaviour in the Federal Republic of Germany was conducted by interviewers of the EMNID institute in 1985 (n = 1267) and 1989 (n = 950). The survey was carried out with women of 15 to 45 years of age. It was the aim of the 1989 study, to look into changes of the last four years generally and with regard to the increasing knowledge about AIDS. As the use of a combination of family planning methods has significantly increased in 1989, the overall percentage went very much beyond 100% (1985: 106.1% vs 1989: 138.5%). Hence, for comparison of the figures, we omitted any sociodemographic weighting. For each method, the percentage of the users is reported independently of any additional method used. The figures (%) for use of reversible methods of contraception 1985 vs 1989 were as follows: the pill (52.2/61.9), condom (10.0/24.8), IUD (14.1/10.8), withdrawal (5.8/6.6), mini-pill (1.7/6.5), NFP (8.8/6.0), locally applied chemical device (2.6/5.2), vaginal diaphragm (3.0/3.0). The frequency of sterilisation was 6.9 vs 5.7%; the frequency of unwanted pregnancies 26.6 vs 20.9%. 12.3% of the women aged 18-45 years stated, that family planning behaviour has changed in the last two years. 1/3 of these declared, that AIDS has played an important part in their decision. Answers to other questions are compared 1985 vs 1989, like "reasons for selecting a particular method", "need for use of contraceptives", "frequency of unwanted pregnancies" and "importance of natural methods".

Acquired Immunodeficiency Syndrome↗

PubMed1991

Validity of the captopril test for identifying correctable unilateral renovascular hypertension.

In order to validate the captopril test for identification of patients with renovascular hypertension (RVH), we performed the test with 118 patients suspected of suffering from RVH who were receiving antihypertensive medication. On the basis of 44 patients with proven RVH and 74 patients with primary hypertension (PH), the sensitivity, specificity and posterior probability for the captopril test were calculated separately for patients undergoing and not undergoing diuretic therapy. An absolute rise in plasma renin activity (PRA) and a relative rise in PRA served as discriminating indicators. The absolute increase of PRA after captopril administration in the absence of long-term therapy with diuretics yielded the best posterior probability in the one-dimensional model, with a sensitivity of 89% and a specificity of 97%. Linking of the variables "absolute" and "relative rise of PRA" reduced the misclassification rate to 5%. This validation allows an accurate distinction between RVH and PH on the basis of the captopril test even when antihypertensive therapy is not suspended (except for ACE inhibitors and diuretics).

Adult↗

PubMed1989

Reliability of different temporary myocardial pacing leads.

Temporary myocardial pacing leads are routinely used for diagnosis and treatment of postoperative arrhythmias following open-heart surgery. The intention of this study is to compare five different electrodes for reliability during the postoperative period. A standardised technique of implantation was used to place 147 ventricular and 81 atrial wire electrodes in 149 patients. During operation and then daily over the next ten days, the stimulation threshold, P- and R-wave sensing, and impedance were measured with a pacing system analyser to evaluate the reliability of the pacing and sensing function. Five measurements were taken at each time; the mean values were statistically analysed. The number of failures in pacing and sensing and the course of the tested parameters during the postoperative period were compared. As a result, bipolar pacing leads (Osypka TME 64a/66a) proved to be more reliable than unipolar wires (Ethicon HD 12S, Osypka TME 60/60a), particularly in atrial sensing. Also the Medtronic 6400/6500 showed good reliability for the ventricle, so that they can be recommended for VVI-mode pacing. In conclusion, for reliable function during the postoperative course up to 10 days a specially developed bipolar temporary pacemaker electrode can be recommended for both atrial and ventricular or sequential pacing.

Differential Threshold↗