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Biomedical subjects

J Malicki

Publications and source records attributed to J Malicki.

At least 19 recordsLinked to original sources
PubMed2005

The efficacy and reliability of lung protection during total body irradiation of patients with disseminated malignancies.

The main problem in total body irradiation (TBI) is obtaining a homogenous dose distribution inside the whole irradiated body and ensuring appropriate dose reduction in the lungs. The process of irradiation should be comfortable for the patients and repeatable despite the size and age diversity among patients. The aim of this paper was 1) to check accuracy of the applied dose algorithm and reliability of the measurement technique used in the lung region during TBI taken alternatively on a Cobalt-60 unit and on 15 MV linear accelerators, and 2) to check if the described methodology made it possible to obtain reproducibly of the lowered level of the dose to the lungs for a diverse group of patients. TBI was performed as a preparatory regiment in children and adults with disseminated malignancies undergoing bone marrow transplantation (a dose of 12.6 Gy in the midline/central beam axis). Two consecutive groups of patients were retrospectively included in the study: 15 irradiated with Cobalt-60 and 15 with 15 MV photons. The doses were evaluated for three sections passing through the middle of the lungs and at their upper and lower sides. Two types of detectors: semiconductor and thermoluminescent ones were used simultaneously. The measured doses were evaluated statistically to reveal agreement between readings of the two types of detectors and agreement between the measured doses and those previously calculated. The results of measurements exhibited a not Gaussian-type distribution (dissymmetry). The Wilcoxon-type test revealed compliance between the doses measured with thermoluminescent (TL) and semiconductor (SEM) detectors for all sections passing through the lungs (p>0.05), excluding the lung exit (middle and lower sides) with the Cobalt therapy. The t-Student test used to compare the measured doses with those previously calculated revealed agreement (p>0.05) between the measured doses and those calculated for all lung sections for the 15 MV photon therapy, while for Cobalt therapy such an agreement was at some points doubtful. The calculation algorithm and measurement techniques have proved to be correct, which was revealed by agreement between the doses measured and those calculated. The shielding of the lungs during both types of fields was effective and reproducible as indicated by agreement between the doses measured with the two types of detectors. Better agreement between the measured and calculated doses was found for 15 MV photons than for the Cobalt unit.

Algorithms↗
PubMed2004

How the implementation of an in-vivo dosimetry protocol improved the dose delivery accuracy in head and neck radiotherapy.

Doses were measured in-vivo at the entrance using semiconductor detectors for patients with head and neck tumors. Regular measurements started on January 1st and continued till June 30th, 2001. Then the evaluation of the discrepancies between the measured and calculated doses was made, and it resulted in the changes in the protocol of in-vivo dosimetry made effective by February 1st, 2002. The collection of the measurements was censored by January 30th 2003. The number of patients in the two groups was 285 (1st) and 407 (2nd), respectively. The results exhibited the not-Gaussian distribution of the measured doses in both groups. The average number of dose checks per patient increased from 4.9 to 6.0 (1st vs. 2nd group). The mean relative difference between the measured and calculated doses was: -1.5% vs. -0.5%, whereas the standard deviation (1 SD) decreased from 6.1% to 5.6%. The Mann-Whitney U test detected a significant difference between the 1st and the 2nd group (p=0.00000), which justified the conclusion that the changes implemented in the protocol improved dose delivery accuracy and reproducibility of irradiation.

Calibration↗
PubMed2003

Thermoluminescent dosimetry in rotary-dual technique of the total skin electron irradiation.

The aim of the study was to discuss the results of thermoluminescent dosimetry (TLD) in rotary-dual technique of the total skin electron irradiation (TSEI RD), to confirm beam calibration and monitor unit calculations and to provide data for making clinical decisions. Between May 2001 and April 2002, in 3 cases of mycosis fungoides, 736 dosimetric checks were performed in 34 points at the skin. CaF2:MnTLD-400 cubes (1/8"x1/8"x0.015") were used for in vivo dosimetry. Doses were computed and analyzed for all locations. Percent of described dose and SD for the following localizations from 34 points were: anterior abdomen (reference point) 100+/-6%, upper back 100+/-8%, right calf 98+/-10%, left foot (mid dorsum) 97+/-8%, posterior neck 93+/-6%, right hand (mid dorsum) 78+/-10%, hand fingers 57+/-10%, top of right shoulder 56+/-14%, left groin 35+/-20%, perineum 22+/-17%. The correlations between patient's height and measured doses were sufficient for the following localizations: scalp (top rear), occiput, elbows, hand fingers and hands (mid dorsum). The correlations between obesity index and measured doses were sufficient for the following localizations: shoulders and lateral neck, groins, and perineum. Dosimetric checks at the reference point confirm that our beam calibration technique and monitor unit calculation are accurate. TLD shows that for some parts of the skin such as shoulder, hands and perineum boost fields were required. The correlations with obesity index and height for several sites suggest that boost fields must be customized for each patient.

Adult↗
PubMed2001

A mutation of early photoreceptor development, mikre oko, reveals cell-cell interactions involved in the survival and differentiation of zebrafish photoreceptors.

To gain insight into mechanisms involved in photoreceptor development, we characterized a zebrafish mutation in the mikre oko locus that produces early loss of photoreceptor cells. mikre oko photoreceptors lose their elongated morphology at the time of wild-type outer segment formation and undergo cell death within a few days. To investigate whether this phenotype involves cell-cell interaction defects, we performed analysis of genetically mosaic animals. Interactions of mikre oko photoreceptors with wild-type cells rescue several aspects of the mutant phenotype. When placed in a wild-type environment, mikre oko photoreceptor cells retain elongated morphology and survive longer. Moreover, although mutant mikre oko photoreceptor outer segments develop only infrequently and are usually disorganized, mikre oko cone and rod cells in mosaic retinas develop robust outer segments that closely resemble the wild type. In contrast to the outer segments, the proximal regions of mikre oko photoreceptor cells, including their inner segments, the nuclear regions, and the synaptic termini, retain the mutant appearance. mikre oko outer segment rescue is not mediated by interactions with the retinal pigment epithelium. These studies demonstrate that the differentiation of outer segments is surprisingly independent from the more proximal photoreceptor cell features and that outer segment development includes retinal pigment epithelium-independent cell-cell interactions.

Animals↗
PubMed2001

Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina.

Mutation of the glass onion locus causes drastic neuronal patterning defects in the zebrafish retina and brain. The precise stratified appearance of the wild-type retina is absent in the mutants. The glass onion phenotype is first visible shortly after the formation of optic primordia and is characterized by the rounding of cells and disruption of the ventricular surface in the eye and brain neuroepithelia. With exception of the dorsal- and ventral-most regions of the brain, neuroepithelial cells lose their integrity and begin to distribute ectopically. At later stages, the laminar patterning of retinal neurons is severely disrupted. Despite the lack of lamination, individual retinal cell classes differentiate in the glass onion retina. Mosaic analysis reveals that the glass onion mutation acts cell nonautonomously within the retina and brain, as neuroepithelial cell morphology and polarity in these tissues are normal when mutant cells develop in wild-type hosts. We conclude that the glass onion mutation affects cell-cell signaling event(s) involved in the maintenance of the neuroepithelial cell layer shortly after its formation. The disruption of neuroepithelial integrity may be the cause of the neuronal patterning defects following neurogenesis. In addition, the expression of the glass onion phenotype in a subset of neuroepithelial cells as well as its onset following the initial formation of the neuroepithelial sheets indicate the presence of genetically distinct temporal and spatial subdivisions in the development of this histologically uniform tissue.

Animals↗
PubMed2001

Improvement of counting helminth eggs with internal standard.

The sanitary regulations introduce a requirement for parasitological control of sewage water used for irrigation and fertilisation of crops. The existing methods of estimation of helminth eggs, based on the coproscopic method using sedimentation, desorption, centrifugation and flotation of the material, allow for only 30-75% efficiency. The aim of this paper is to present an improved quantitative estimation method. The proposed method is based on an internal standard. A predetermined number of eggs of Ascaris lumbricoides suis L is coloured with crystalline violet. These marked eggs are added to sample being examined. Counting the marked eggs in the sample and comparing them with their introduced number allows to estimate the efficiency of the procedure. This results in an increase in the efficiency of the method to 100%. It is possible to calculate the real number of helminth eggs in the sample on the basis of the estimated efficiency of the procedure. The sensitivity of the proposed method is at the level of about 0.4 ppm. The necessary number of replications in the method is about 10 times lower than that in the existing methods. The number of natural (not coloured) eggs does not influence the efficiency of the method with an internal standard.

Animals↗
PubMed2001

Cobalt 60 versus 15 MeV photons during total body irradiation: doses in the critical organs and complexicity of the procedure.

OBJECTIVES: The aim of this work was to compare the doses in critical organs, treatment duration, patient comfort and personnel workload during total body irradiation carried out alternatively with a Cobalt 60 and with 15 MeV photons at linear accelerator. PATIENTS AND METHODS: Twenty consecutive patients irradiated with a Cobalt unit and twenty irradiated with 15 MeV photons in a linear accelerator were used for comparison of the dose delivered. Each irradiation was repeated eight times during four consecutive days up to a total dose of 12.6 Gy in the whole body (below 10 Gy in the lungs). Lateral fields were used in six fractions, and anterior-posterior fields in two fractions. An electron boost to the thorax wall was added. Doses were calculated and measured in-vivo in ten transverse sections. RESULTS: For the patient taken as an example doses in the middle of the lungs were 10.7 Gy for Co-60 and 11.2 Gy for 15 MeV photons without compensators and 9.6 Gy, 9.6 Gy respectively when compensators were applied. Mean doses in the lungs in the group were 9.5 Gy for Co-60 and 9.7 Gy for X 15 MeV, respectively. Duration of the treatment was shorter with the use of the 15 MeV than that with Co-60 by about 20%. Repositioning of the patient during two fractions with the use of X 15 MeV could be eliminated and therefore the patient's comfort increased.

Cobalt Radioisotopes↗
PubMed2000

Genetically modified tumour vaccines (GMTV) in melanoma clinical trials.

Since melanoma is a model immunogenic malignancy incurable in the disseminated phase of its natural course different immunotherapeutic approaches are tested in clinical trials. A number of tumour vaccines genetically modified (GMTV), with various immunostimulatory factors, are tested in phase I/II clinical trials. These factors include cytokines, tumour antigens (TA), costimulatory molecules or HLA antigens. We have designed a novel, mixed auto/allogeneic cellular melanoma vaccine modified with the IL-6 and the sIL-6R genes. Preclinical studies in a mouse model demonstrated that the IL-6/sIL-6R based vaccine is able to elicit efficient anti-tumour responses, mediated by CD8+ and NK cells, which resulted in inhibition of the tumour growth, metastases formation and prolonged survival of the animals treated. Irradiation of vaccine cells does not only lead to their sterilisation but also causes increased secretion of exogenous IL-6 and sIL-6R. Since January 1996 we have vaccinated more than one hundred metastatic melanoma patients. Promising clinical results (22% CR+PR, 32% SD) and the evidence of immune responses in the vaccinated patients have prompted us to design a phase III clinical trial which is to be open in 2000.

Animals↗
PubMed2000

Harnessing the power of forward genetics--analysis of neuronal diversity and patterning in the zebrafish retina.

The seven major cell classes of the vertebrate retina are organized with remarkable precision into distinct layers. The appearance of this architecture during embryogenesis raises two questions of general importance. How do individual cell classes acquire their specialized structures and functions if they all originate from a morphologically uniform cell population? What mechanisms are responsible for the formation of such a complex and exact pattern? Recent advances present an opportunity to apply the tools of forward genetic analysis to identify mutations that affect these mechanisms in zebrafish. Molecular characterization will follow, providing insight into the basis of neuronal patterning in the vertebrate CNS.

Animals↗
PubMed2000

The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells.

Embryos from mutagenized zebrafish were screened for disruptions in retinal lamination to identify factors involved in vertebrate retinal cell specification and differentiation. Two alleles of a recessive mutation, young, were isolated in which final differentiation and normal lamination of retinal cells were blocked. Early aspects of retinogenesis including the specification of cells along the inner optic cup as retinal tissue, polarity of the retinal neuroepithelium, and confinement of cell divisions to the apical pigmented epithelial boarder were normal in young mutants. BrdU incorporation experiments showed that the initiation and pattern of cell cycle withdrawal across the retina was comparable to wild-type siblings; however, this process took longer in the mutant. Analysis of early markers for cell type differentiation revealed that each of the major classes of retinal neurons, as well as non-neural Müller glial cells, are specified in young embryos. However, the retinal cells fail to elaborate morphological specializations, and analysis of late cell-type-specific markers suggests that the retinal cells were inhibited from fully differentiating. Other regions of the nervous system showed no obvious defects in young mutants. Mosaic analysis demonstrated that the young mutation acts non-cell-autonomously within the retina, as final morphological and molecular differentiation was rescued when genetically mutant cells were transplanted into wild-type hosts. Conversely, differentiation was prevented in wild-type cells when placed in young mutant retinas. Mosaic experiments also suggest that young functions at or near the cell surface and is not freely diffusible. We conclude that the young mutation disrupts the post-specification development of all retinal neurons and glia cells.

Animals↗
PubMed1999

The accuracy of dose determination during total body irradiation.

AIM: The aim of this work was to estimate the error in dose calculations, to check the agreement between the measured and calculated doses and to analyse dose discrepancies in the group of patients undergoing total body irradiation. PATIENTS AND METHODS: A combination of lateral and anterior-posterior fields was used in 8 fractions and on 4 consecutive days. Doses were preliminarily calculated and then measured in vivo by thermoluminescent, semiconductor and ionization dosimeters attached to the body in 10 representative transverse cross-sections. Calculations and measurements were carried out for the beam at the body entry and exit. The error in dose calculations was estimated for each reference point. Dose deviations between calculations and measurements were analysed using the Student's t-test. RESULTS: The error in preliminary dose calculations ranged from 3% to 15% (Table 1). Standard deviations of the measurements and percent deviations from the calculations exceeded 10% only for the lung and neck exits (Table 3). Average thermoluminescent readings were 6% higher than the corresponding semiconductor readings. The measured doses fitted the calculated values within the limit of error, except for the lung, head and neck exits for the whole group, depending on the type of fields used (Table 4).

Abdomen↗
PubMed1999

Development of the retina.

As in other vertebrate species, the zebrafish retina is simpler than other regions of the central nervous system. This relative simplicity along with rapid development, and accessibility to genetic analysis make the zebrafish retina an excellent model system for studies of neurogenesis in the vertebrate CNS. Several genetic screens have led to the isolation of an impressive collection of mutants affecting the retina and the retinotectal projections in zebrafish. A variety of techniques and markers are available to study the isolated mutants. These include several antigen- and transcript-detection methods, retrograde and anterograde labeling of neurons, blastomere transplantations, H3 labeling, and others. As past genetic screens have achieved a rather low level of saturation, the current collection of mutants can only grow in the future. Morphological and behavioral criteria have been successfully applied in zebrafish to search for defects in spinal development. In future genetic screens, progressively more sophisticated screening approaches will make it possible to detect very subtle changes in the retinal development. The remarkable evolutionary conservation of the vertebrate eye provides the basis for using the zebrafish as a model system for the detection and analysis of genetic defects potentially related to human eye disorders. Some of the genetic defects of the zebrafish retina indeed resemble human retinopathies. As the genetic analysis of the vertebrate visual system is far from being complete and new techniques are being introduced at a rapid pace, the zebrafish embryo will become increasingly useful as a model for studies of the vertebrate retina.

Animals↗
PubMed1999

oko meduzy mutations affect neuronal patterning in the zebrafish retina and reveal cell-cell interactions of the retinal neuroepithelial sheet.

Mutations of the oko meduzy (ome) locus cause drastic neuronal patterning defect in the zebrafish retina. The precise, stratified appearance of the wild-type retina is absent in the mutants. Despite the lack of lamination, at least seven retinal cell types differentiate in oko meduzy. The ome phenotype is already expressed in the retinal neuroepithelium affecting morphology of the neuroepithelial cells. Our experiments indicate that previously unknown cell-cell interactions are involved in development of the retinal neuroepithelial sheet. In genetically mosaic animals, cell-cell interactions are sufficient to rescue the phenotype of oko meduzy retinal neuroepithelial cells. These cell-cell interactions may play a critical role in the patterning events that lead to differentiation of distinct neuronal laminae in the vertebrate retina.

Animals↗
PubMed1998

Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish.

Vertebrate eye development in the anterior region of the neural plate involves a series of inductive interactions dependent on the underlying prechordal plate and signals from the midline of the neural plate, including Hedgehog. The mechanisms controlling the spatiotemporal expression pattern of hedgehog genes are currently not understood. Cyclopia is observed in trilobite (tri) and knypek (kny) mutants with affected convergent extension of the embryonic axis during gastrulation. Here, we demonstrate that tri mutants show a high frequency of partial or complete cyclopia, kny mutants exhibit cyclopia infrequently, while knym119 trim209 double-mutant embryos have dramatically reduced convergent extension and are completely cyclopic. We analyzed the relationships between the convergent extension defect, the expression of hedgehog and prechordal plate genes, and the formation of cyclopia in knym119 and trim209 mutants. Our results correlate the cyclopia phenotype with the abnormal location of hh-expressing cells with respect to the optic primordium. We show that cyclopia in these mutants is not due to an incompetence of tri and kny cells to respond to Hedgehog signaling. Rather, it is a consequence of exceeding a critical distance (>40-50 micrometer) between hedgehog-expressing cells and the prospective eye field. We hypothesize that at this distance, midline cells are not in an appropriate position to physically separate the eye field and that HH and other signals do not reach the appropriate target cells. Furthermore, tri and kny have overlapping functions in establishing proper alignment of the anterior neural plate and midline cells expressing shh and twhh genes when the partitioning of the eye primordium takes place.

Animals↗