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Biomedical subjects

A Kowalczyk

Publications and source records attributed to A Kowalczyk.

At least 19 recordsLinked to original sources

In vitro comparative antileukemic activity of various glucocorticoids in childhood acute leukemia.

Resistance to glucocorticoids is nowadays one of the strongest adverse risk factors in the treatment of childhood acute lymphoblastic leukemia (ALL). Differential in vitro antileukemic activity of various glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and myeloblastic leukemia was determined by means of the MTT assay in 49 successfully tested samples of childhood acute leukemia. The equivalent antileukemic concentrations of respective drugs against lymphoblasts in de novo ALL samples were: 35 microM of hydrocortisone; 8 microM of prednisolone; 1.6 microM of methylprednisolone; 0.47 microM of dexamethasone and 0.23 microM of betamethasone. In comparison to initial ALL samples, the group of relapsed ALL was more resistant to: prednisolone (38-fold, p=0.004), dexamethasone (>32-fold, p=0.004), methylprednisolone (37-fold, p=0.039), betamethasone (38-fold, p=0.018) and hydrocortisone (33-fold, p=0.030). The group of acute myeloid leukemia (AML) samples were resistant to: prednisolone (>83-fold, p<0.001), dexamethasone (>32-fold, p<0.004), methylprednisolone (>65-fold, p=0.003), betamethasone (>66-fold, p=0.004) and hydrocortisone (61-fold, p=0.007), when compared to ALL at presentation. A significant cross-resistance between all used glucocorticoids as well as between glucocorticoids and other tested anti-leukemic drugs was found. In some individual cases in vitro glucocorticoid cross-resistance was less pronounced and relatively good antileukemic activity of betamethasone was observed.

Antineoplastic Agents↗

Penile metastases from urogenital primaries.

Metastatic tumors of the penis are rare. They are usually secondary to primaries of the genitourinary and gastrointestinal tracts. This entity is usually accompanied by distressing symptoms like dysuria, pain, induration, swelling of the penis and priapism, making immediate intervention necessary. Different methods of treatment are used to achieve the palliative effect: local surgical excision, penis amputation, radiotherapy or chemotherapy. Nevertheless, the prognosis is poor, because the disease is already disseminated and in most cases other metastases will occur soon.

Aged↗

The combined effect of IDA and glutaraldehyde on the properties of human erythrocytes.

The effect of IDA and glutaraldehyde on the properties of human erythrocytes was examined by Electron Spin Resonance spectroscopy and fluorescence measurements. In this study glutaraldehyde was used as the agent linking the drug to the erythrocyte membrane. We have demonstrated that idarubicin (IDA) alone caused only negligible changes of the membrane fluidity. When IDA preincubated erythrocytes were treated with glutaraldehyde, the alterations in the fluidity were observed in the polar parts as well as in the deeper regions of the cell membrane. The incorporation of drug and glutaraldehyde into human erythrocytes also caused conformational alterations of membrane cytoskeletal proteins and changes in the internal viscosity of the cells. Our data suggest that glutaraldehyde in idarubicin-pretreated erythrocytes may potentiate the drug toxicity leading to significant perturbations in the organization of the plasma membrane lipids and proteins.

Antibiotics, Antineoplastic↗

Point mutations induced by 1,2-epoxy-3-butene N1 deoxyinosine adducts.

The National Toxicology Program has recently classified 1,3-butadiene (BD) as a human carcinogen. BD is metabolized to the intermediates 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-dihydroxy-3,4-epoxybutane. All three metabolites have been implicated in producing specific types of DNA damage and as genotoxic agents in mice, rat, and human cells. This study has focused on EB-induced N1 deoxyinosine lesions that are formed by deamination of deoxyadenosine following reaction of the epoxide at the N(1) position. The R and S stereoisomers of this lesion were incorporated site-specifically within the context of an 11-mer oligodeoxynucleotide, incorporated into M13mp7L2 single-stranded DNA, and transfected into E. coli. Both stereoisomers modestly reduced plaque-forming ability, indicating that neither lesion presents a base modification that cannot be bypassed. The resulting plaques were assessed for point mutations using differential hybridization and DNA sequence analyses. The overall mutagenic spectrum revealed that the N1 adducts were highly mutagenic (approximately 90% per replication cycle), causing a predominance of A --> G transitions.

Adenine↗

First-order statistics of human stabilogram.

We investigated the statistical properties of the centre of pressure (COP) vector during quiet standing, as measured on a force platform. To derive a statistical model for the data, the COP vector, locally averaged COP, and deviations from the average COP were analysed. Whereas indefinite multimodal distributions for the components of the COP were observed, the density functions of deviation from the averaged COP had reproducible properties. The anterior-posterior and mediolateral components of the deviations had in common that they were correlated variables with a non-circular statistic. The main axes of the equiprobability density curves were rotated with respect to the natural anterior-posterior and mediolateral directions. By means of more detailed statistical analysis of the data, two distinct populations of subjects were identified. In some cases we have found Gaussian distributions of the components of deviation from the average COP. In most cases the statistics was non-Gaussian. The average contrast, a new dimensionless characteristic quantity, independent of platform calibration, was introduced as a useful indicator of non-Gaussian effects in the postural control system.

Humans↗

Synthesis and characterization of oligodeoxynucleotides containing an N1 beta-hydroxyalkyl adduct of 2'-deoxyinosine.

Hydroxyethyl adducts arising by the reactions of simple epoxides at the N1 position of adenine nucleosides can deaminate to give the inosine analogues which, if formed in DNA, are suspected of being highly mutagenic. A method has been developed for synthesis of oligonucleotides containing N1-adducted 2'-deoxyinosines. The 2'-deoxyinosine adduct of 3,4-epoxy-1-butene was prepared from (+/-)-4-acetoxy-3-bromo-1-butene and tetraisopropyldisiloxanediyl-protected 2'-deoxyinosine with base. The 2'-deoxyinosine derivative was then incorporated into the oligodeoxynucleotide sequence 5'-d(CGGACXAGAAG)-3' (X = N1-(1-hydroxy-3-buten-2-yl)-2'-deoxyinosine).

Amino Acid Sequence↗

[Environmental radiation exposure of a thyroid cancer patient resulting from adjuvant iodine radiotherapy].

The aim of the study was to evaluate radiation risk in the environment of patients treated with 131I as an ablative therapy following radical surgery for the differentiated thyroid cancer. The activities of radioiodine used in this form of therapy approximate 2.8 GBq (76 mCi) and the in cases of the cancer metastases to other organs may be as high as 7.4 GBq (200 mCi). Dose equivalent rates were estimated in nine seated patients at the level of the thyroid close to the gland surface, and 0.5 and 1 m away from it. The measurements were performed at one, 24, 48, 72, 96, 120, 144, and 168 hours after the injection of 131I. The dose equivalent rates at various distances from the thyroid surface at different times were approximated with the exponential function by the least square method. Then, the dose equivalents were calculated from the moment of 131I application to the moment of the total removal of the isotope from the organism. From this relation, time intervals after which the annual threshold doses of 1, 5, and 50 mSv would be exceeded were computed as the function of the applied 131I activity. The results of the present study indicate that attendants of the patients treated with 131I will not be exposed to the doses of ionising radiation exceeding the acceptable annual thresholds provided with the limited time intervals. In addition, the present results may be useful in elaborating procedures of dealing with and handling the patients during their stay at hospital, at home, and at work.

Adult↗

[Evaluation of the relationship between chosen factors and results of whole body scintigraphy with 131I in patients with differentiated thyroid cancers].

Treatment and diagnostics with 131I play an important role in patients with differentiated thyroid cancer (DTC) after thyreoidectomy. The aim of the study was to assess the influence of some factors on ablative therapy results. Fifty seven patients with DTC were investigated (44 females--mean age 46.6 yrs, 13 males--mean age 55.6 yrs.). Papillary thyroid cancer was diagnosed in forty five patients (79%) however, follicular thyroid cancer in the others (21%). We performed post-therapeutic whole-body scan (WBS) after high fixed doses of 131I (median = 75 mCi) and six months later diagnostic WBS (mean 4.3 mCi) in every patient. Postoperative radioiodine uptake, levels of TSH and thyroglobulin (Tg) serum concentrations were assessed after thyroid hormones withdrawal before imaging. The absence of radioiodine uptake in the thyroid bed (effective ablation) was observed in 64.9% of patients. In other cases scans showed significantly diminished uptake of the tracer in the remnants. Statistically significant difference in TSH levels before and after radioiodine therapy (75.6 vs. 106.7 microIU/ml, p < 0.001) was found in all patients. However, effectiveness of the ablative therapy did not depend on radioiodine uptake, TSH and Tg levels before radioiodine treatment.

Adenocarcinoma, Follicular↗

Butadiene-induced intrastrand DNA cross-links: a possible role in deletion mutagenesis.

To initiate studies designed to identify the mutagenic spectrum associated with butadiene diepoxide-induced N(2)-N(2) guanine intrastrand cross-links, site specifically adducted oligodeoxynucleotides were synthesized in which the adducted bases were centrally located within the context of the human ras 12 codon. The two stereospecifically modified DNAs and the corresponding unmodified DNA were ligated into a single-stranded M13mp7L2 vector and transfected into Escherichia coli. Both stereoisomeric forms (R, R and S,S) of the DNA cross-links resulted in very severely decreased plaque-forming ability, along with an increased mutagenic frequency for both single base substitutions and deletions compared with unadducted DNAs, with the S,S stereoisomer being the most mutagenic. Consistent with decreased plaque formation, in vitro replication of DNA templates containing the cross-links by the three major E. coli polymerases revealed replication blockage by both stereoisomeric forms of the cross-links. The same DNAs that were used for replication studies were also assembled into duplex DNAs and tested as substrates for the initiation of nucleotide excision repair by the E. coli UvrABC complex. UvrABC incised linear substrates containing these intrastrand cross-links with low efficiency, suggesting that these lesions may be inefficiently repaired by the nucleotide excision repair system.

Adenosine Triphosphatases↗

Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus.

Understanding of biological function of AP-1 transcription factor in central nervous system may greatly benefit from identifying its target genes. In this study, we present several lines of evidence implying AP-1 in regulating expression of tissue inhibitor of metalloproteinases-1 (timp-1) gene in rodent hippocampus in response to increased neuronal excitation. Such a notion is supported by the findings that timp-1 mRNA accumulation occurs in the rat hippocampus after either kainate- or pentylenetetrazole-evoked seizures with a delayed, in comparison with AP-1 components, time course, as well as with spatial overlap with c-Fos protein (major inducible AP-1 component) expression. Furthermore, AP-1 sequence derived from timp-1 promoter is specifically bound by hippocampal AP-1 proteins after treating the rats with either pro-convulsive agent. Finally, timp-1 promoter responds to excitatory activation both in vivo, in transgenic mice harboring the timp-LacZ gene construct, and in vitro in neurons of the hippocampal dentate gyrus cultures. These findings suggest that the AP-1 transcription factor may exert its role in the brain through affecting extracellular matrix remodeling.

Animals↗

[The role of the spontaneous occurrence of Pulfrich's stereophenomenon in the diagnosis of demyelinating diseases of the central nervous system].

PURPOSE: Checking the usefulness of the spontaneous occurrence of Pulfrich's stereophenomenon in the diagnosis of demyelinating diseases. MATERIAL AND METHODS: Research embraced 22 patients with visual disturbances (including 9 patients with retrobulbar neuritis and others with anterior ischaemic neuropathy, central retinal vein occlusion, intrabulbar optic neuritis and traumatic atrophy of the optic nerve). The research also embraced 27 patients with demyelinating diseases (sclerosis multiplex). RESULTS: Spontaneous occurrence of Pulfrich's stereophenomenon was reported in 9 retrobulbar neuritis patients. It was also reported in 24 demyelinating patients. CONCLUSION: This simple Pulfrich's pendulum test is positive in 92% of demyelinating patients, including all patients with SM and retrobulbar neuritis.

Demyelinating Diseases↗

Potential misevaluation of the ground-state dissociation constant from fluorimetric titrations: application to the ion indicators SBFI, PBFI, and fura-2.

A test based on time-resolved fluorescence experiments is proposed to assess the interference of an excited-state reaction with the fluorimetric determination of the ground-state dissociation constant Kd of ion [symbol: see text] fluorescent indicator complexes. If an inflection point occurs in the plot of the fluorescence signal vs -log [ion] in the concentration range of the ion where both decay times are invariant, this inflection point can be associated with the correct Kd. In contrast, the inflection point(s) in the concentration range where the decay times vary cannot be attributed to Kd. The test is applied to the fluorescent ion indicators SBFI (for Na+), PBFI (for K+), and Fura-2 (for Ca2+). In all three cases the decay times are invariant in the physiological concentration ranges of the respective ions, indicating that the fluorimetrically determined Kd values are actually the true Kd values.

Benzofurans↗

[Use of Pulfrich's stereo-phenomenon in determining stereoscopic vision].

PURPOSE: To check whether a test based on Pulfrich's stereophenomenon can be applied to determine stereopsy. MATERIAL AND METHODS: The group of 24 patients with normal visual acuity and stereopsy and 15 with ambylopia without stereopsy were tested with Pulfrich's pendulum test. RESULTS: This method yielded 24 positive and 15 negative cases confirming the previous assessments. Neither false positive nor false negative cases were recorded. CONCLUSION: The simplicity and reliability of this method in determining stereopsy provide arguments for its widespread use.

Adult↗

Photophysics of the fluorescent Ca2+ indicator Fura-2.

The photophysics of the complex forming reaction of Ca2+ and Fura-2 are investigated using steady-state and time-resolved fluorescence measurements. The fluorescence decay traces were analyzed with global compartmental analysis yielding the following values for the rate constants at room temperature in aqueous solution with BAPTA as Ca2+ buffer: k01 = 1.2 x 10(9)s-1, k21 = 1.0 x 10(11) M-1 s-1, k02 = 5.5 x 10(8) s-1, k12 = 2.2 x 10(7) s-1, and with EGTA as Ca2+ buffer: k01 = 1.4 x 10(9) s-1, k21 = 5.0 x 10(10) M-1 s-1, k02 = 5.5 x 10(8) s-1, k12 = 3.2 x 10(7) s-1. k01 and k02 denote the respective deactivation rate constants of the Ca2+ free and bound forms of Fura-2 in the excited state. k21 represents the second-order rate constant of binding of Ca2+ and Fura-2 in the excited state, whereas k12 is the first-order rate constant of dissociation of the excited Ca2+:Fura-2 complex. The ionic strength of the solution was shown not to influence the recovered values of the rate constants. From the estimated values of k12 and k21, the dissociation constant K*d in the excited state was calculated. It was found that in EGTA Ca2+ buffer pK*d (3.2) is smaller than pKd (6.9) and that there is negligible interference of the excited-state reaction with the determination of Kd and [Ca2+] from fluorimetric titration curves. Hence, Fura-2 can be safely used as an Ca2+ indicator. From the obtained fluorescence decay parameters and the steady-state excitation spectra, the species-associated excitation spectra of the Ca2+ free and bound forms of Fura-2 were calculated at intermediate Ca2+ concentrations.

Biophysical Phenomena↗

Analysis of time-resolved emission spectra of oriented phycobilisomes.

The polarized time-resolved (in ps range) fluorescence spectra of phycobilisomes obtained from cyanobacteria Tolypothrix tenuis embedded in poly(vinyl alcohol) films and oriented by film stretching have been analysed. Fluorescence spectra were deconvoluted on Gaussian components supposing the same positions of components maxima in three sets of time-resolved spectra taken in natural and polarized light. A good fit of the experimental and calculated spectra was obtained when using the following maxima: 580 and 595 nm in the phycoerythrin region, 634 and 650 nm in the phycocyanin region, 660 and 680 nm in the allophycocyanin region. The area under curve of the Gaussian component vs. time gives the shape of rise and decay of emission of chromophores contributing to the given component. These kinetics were analysed using several model functions. The experimental excitation profile was convoluted with a multiexponential model individually or "globally" e.g. assuming the same lifetime values for the given species in all sets of spectra. The Foerster-Hauser types of two- and three-dimensional models we also convoluted with excitation profile and fitted to the decay of primarily excited species. The first acceptor decay can be described well by the Foerster-Hauser models or by a monoexponential function. The accuracy of fit in either case of three- and two-dimensional Foerster-Hauser function is similar. The fluorescence rise and decay of the next species in a donor-acceptor chain can be analysed in terms of two or three exponential functions. Obtained lifetimes of fluorescence are similar to those reported in literature. The results suggest that there are more than one chain of excitation donors and acceptors in the phycobilisomes of cyanobacteria Tolypothrix tenuis.

Journal Article↗

[Toxic-dynamics of lead compound and zinc compound in the evaluation of experimental animal behavior].

The aim of the studies was to determine the effect of lead and zinc compound on the mice behaviour. The animals were given intraperitoneally the solution of lead acetate and zinc chloride for 30 days. The mice were subjected to the tests determining their effects on the coordination of movements, the spontaneous motility, the cognitive motility and the motility in the straight rod test as well as on the body temperature. Due to the prolonged exposition to the action of lead and zinc compounds the inhibiting effect of those substances in the central nervous system in the maximal doses was proved while in the minimal doses the antagonistic action of zinc compound was observed. The nerve conduction disorders in the peripheral and central nervous system after the administration of the maximal doses of lead compound may be due to the inhibiting effect of this compound while the lack of this effect in the minimal doses probably results from the antagonistic action of zinc compound.

Animals↗

Quantitation of S100 protein-positive cells in inflamed and non-inflamed keratoacanthoma and squamous cell carcinoma.

Langerhans cells (LC) were identified and quantitated in non-inflamed keratoacanthoma (KA), inflamed KA, non-inflamed squamous cell carcinoma (SCC), and inflamed SCC, by their content of S100 protein. The number of LCs per high-power field was markedly increased in inflamed KA when compared to the other groups. Using similar methods on frozen sections, the expression of HLA-DR was identified on keratinocytes in KA in areas of inflammation but not in other lesions under study. We hypothesize that increased numbers of LCs in inflamed KA are part of the process which results in tumor regression.

Carcinoma, Squamous Cell↗