Biomedical subjects
R Kordek
Publications and source records attributed to R Kordek.
[Pleomorphic xanthoastrocytoma].
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[Ependymomal neoplasms].
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[Infantile desmoplastic ganglioglioma and desmoplastic cerebral astrocytoma of infancy].
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[Dysembryoplastic neuroepithelial tumor].
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Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases.
Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases.
Comparative evaluation of the expression of cell cycle regulating proteins: cyclin D1, P53 and P21 (WAF1) in colorectal cancer.
Cyclin D1, P53 and P21 (WAF1) are cell cycle regulating proteins, playing a crucial role in oncogenesis of a large number of human malignancies, and loss of activity of P53 and P21 (WAF1) proteins seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. To find out their mutual relations we investigated the expression of cyclin D1, P53 and P21 (WAF1) in 122 colorectal cancers by immunohistochemistry. Positivity for cyclin D1 was found in all the cases (100%), positivity for P53 in 96 cases (70%) and positivity for P21 in 48 cases (39%). Statistical analysis revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and also between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity. These data suggest that in colorectal cancer induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. Wild-type P53, which is undetectable by immunohistochemistry, induces transcriptionally P21 (WAF1) and in tumours it may cause its accumulation, while mutations of the P53 may result in a sufficient increase of intracellular protein having no ability to transactivate P21 (WAF1). Moreover P21 (WAF1) as the main cyclin-dependent kinases (CDKs) inhibitor may also inhibit the activity of the cyclins, thus overexpression of P21 (WAF1) may result in reduced level of cyclin D1.
Membrane-bound paracrystalloid structures in alveolar rhabdomyosarcoma.
We report here a case of an alveolar rhabdomyosarcoma in a 25-year-old woman. Ultrastructural examination revealed a few periodical membrane-bound crystalloids, similar to those regarded as specific for alveolar soft-part sarcoma. Our study provides evidence supporting a myogenic origin of those periodic structures, and simultaneously a myogenic origin of alveolar soft-part sarcoma.
The diagnosis of human prion diseases.
Prion diseases present a wide spectrum of clinical and neuropathological features. In this review, clinical and neuropathological findings are summarized along with criteria for the diagnosis of the molecular-phenotypic subtypes of sporadic Creutzfeldt-Jakob disease (CJD), familial CJD, new variant CJD, iatrogenic CJD, Gerstmann-Straussler-Scheinker disease, fatal familial insomnia and kuru.
Deposition of the prion protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease.
We studied the immunocytochemical distribution of the prion or proteinase-resistant protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease (CJD) in mice. Fifty-one brains were collected up to 22 weeks following intracerebral inoculation with the Fujisaki strain of the CJD agent. Slides were also immunostained for apolipoprotein E (apoE) and glial fibrillary acidic protein. Vacuolar changes with focal astrocytosis first occurred around the needle track at week 2 and later spread along white matter tracks. Until week 12, changes were asymmetrical, affecting more the side of inoculation. Spongiform change and astrogliosis spread subsequently to the gray matter. Time course and intensity of spongiform change and immunocytochemistry for PrP were discrepant: in most brain regions, severe vacuolation preceded immunocytochemically detectable PrP accumulation. PrP deposits in form of small dots were first detectable at week 6 in the area surrounding the needle track. After week 7, plaque-like amorphous PrP deposits were observed in white matter pathways. Finally, PrP was detectable also in basal ganglia and in the dorsal hippocampus (week 13) and in the neocortex (week 17), as the synaptic type of PrP immunopositivity. In the hippocampus, diffuse PrP deposits paralleled spongiform change, while in the cortex severe vacuolation was accompanied only by weak synaptic PrP deposits. Immunocytochemically detectable apoE was restricted to compact plaque-type PrP deposits after week 15. We conclude that disease-specific neuropathology spreads from the needle track along white matter pathways towards the gray matter; in this model, there is some discrepancy between development of tissue pathology and immunocytochemically detectable deposition of PrP. Immunocytochemically detectable apoE deposition follows PrP accumulation.
Immunohistochemistry in diagnostic neuropathology--limitations and interpretations.
Immunohistochemistry is widely used for diagnostic neuropathology, but contrary to some anxieties--it is not method which may replace an experienced pathologist. On the contrary--only an experienced pathologist may use this method safely. If the differential diagnosis is wrong, the results may be misleading. Similarly, the specificity of used antibodies does not guarantee the clearcut differentiation.
Dysembryoplastic neuroepithelial tumor (DNT): an ultrastructural study of six cases.
We report six cases od DNT with a detailed ultrastructural characteristics. The patient age ranged from 7 to 16 years (mean 12), the location was temporal in three cases and frontal, temporooccipital and parietooccipital in each of one remaining cases. The predominant clinical feature in each case was history of episodes of intractable seizures. Histopathologically, the neoplasms were multinodular, each nodule was well-circumscribed and was composed of glioneuronal elements embedded in the variable amount of myxoid matrix. The oligodendroglial-like cells (OLC) predominated in the nodules with some accompanying mature neurons. The nodules were frequently surrounded by small calcifications which could be found also within the tumors. OLCs were immunoreactive for S-100 protein and neurons had the expression of synaptophysin and neurofilament proteins. Ultrastructurally, each tumor consisted of three major elements: neoplastic cells (OLC), elongated processes forming neuropil-like structure and expanded "mucoid" extracellular space: the latter gave an impression of cellular elements floating within it. Neoplastic cells had round, oval or elongated nuclei, no discernible nucleoli and a relatively narrow rim of the cytoplasm. Some nuclei were irregular and invaginated and pseudoinclusions were observed; a part of cytoplasm sequestered within pseudoinclusions often appeared degenerated with large blabs and electron-lucent vesicles, some of these contained in turn semicircular profiles of unknown significance. The second element consisted of innumerable cellular processes. Some of these were elongated and formed stacks connected by symmetrical symmetric or asymmetric adhesive plaque junctions. The others had shorter "neck" containing microtubules, these extended into bullous extensions. Dense-cored vesicles were occasionally observed, in both cytoplasm of neoplastic cells and within processes. In one cell, cross-sectioned annulate lamellae were found. In cytoplasm of a few cells, unusual inclusions reminiscent ribosome-lamellae complexes were observed. These were cylindrical resembling "laboratory tubes" with a cone-like endings. At higher power, walls of the "tubes" resolved into layered structures composed of several laminae; between laminae, ribosome-like structures were visible.
Molecular analysis of PRNP gene in Polish population and in Creutzfeldt-Jakob disease.
In our study we have examined allelic variation of codon 129 among the Polish population as well as Polish and Dutch CJD cases. The open reading frame of the PrP gene was amplified using the polymerase chain reaction (PCR). PCR product was digested with Nsp I and Mae II endonucleases and separated by 2% agarose gel electrophoresis and, finally, sequenced by the Sanger dideoxy-mediated chain-termination method. To obtain population data we have screened 109 unrelated Polish adults. There were 45% of methionine homozygotes, 16% of valine homozygotes and 3% of heterozygotes. Among Polish CJD cases, 75% were methionine homozygous, 12.5% were valine homozygous and 12.5% were heterozygous, whereas among Dutch CJD cases it was 29% of Met/Met and 71% of Met/Val genotypes.
Neuronal loss and apoptosis in experimental Creutzfeldt-Jakob disease in mice.
One of the hallmarks of prion disease--neuronal cell loss, may be accomplished by apoptosis. The aim of this study was to estimate the neuronal cell loss in mice brains with experimental Creutzfeldt-Jakob disease (CJD) and control mice in the comparison with the apoptosis appeared by in situ end labelling (TUNEL) in function of time of post-incubation period and developing of the spongiform changes. The number of neurons was considerably lower in terminally sick animals (20-21 week of incubation period) than in control mice. The mean value of loss of neuronal cell was 32%. The greatest loss (55%) of neurons was noted in the septal nuclei of the paraterminal body and the least lost (16%) in the hypothalamus. We report here, that apoptotic cells are readily detectable in CJD-affected mice brains in time-dependt manner after infection of Fujisaki strain, but the number of apoptotic cells detected by in situ end labelling does not well correlate with the extensiveness of neuronal loss. The degree of apoptosis corresponds to the well developed spongiform changes.
Cytogenetic and proliferative potentials in meningiomas.
Cytogenetic analysis and Ki-67 staining index (SI) were performed on the series of 51 meningiomas, to estimate the relationship between the extent of chromosomal changes and the growth potential of tumors. The tumors were classified according to histological subtype (22 meningiotheliomatous, 15 transitional, 12 fibroblastic and 2 angiomatous) and grade (40 benign, 5 atypical and 6 malignant ones). There was no significant difference in the complexity of chromosomal changes among the histologically distinct tumor subtypes. In contrast, there was a significant association between the number of chromosomal abnormalities and tumor grade. Normal karyotypes were found in 50% and complex in 20% of benign tumors. All grade II or III tumors revealed complex karotype. The tumors classified as benign revealed significantly lower mean Ki-67 SI than atypical or malignant ones (1.6%, 7.4% and 14.7%, respectively). However, within tumors classified as benign, mean Ki-67 SI of these with normal or simple karyotypic changes did not differ significantly from those with complex karyotype (1.6% and 0.9%, respectively). Thus, the extent of genome abnormalities in meningiomas, measured on the chromosomal level, does not relate directly to their proliferative potential.
Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies.
Little is known about the pathogenetic basis of characteristic symptoms in transmissible spongiform encephalopathies (TSEs) such as myoclonus and characteristic EEG hyperactivity. We investigated the GABAergic system and its subpopulations in mice inoculated with experimental scrapie (ME7, RML, 22A strains) and Creutzfeldt-Jakob disease (CJD; Fujisaki strain), to study damage to inhibitory neurons. Since recent studies have shown electrophysiological changes in prion protein (PrP) knockout mice, we also studied mice lacking or overexpressing the PrP gene. Antibodies against glutamic acid decarboxylase (GAD), parvalbumin (PV), calbindin (CB), and calretinin (CR) were used to stain GABAergic neurons, and isolectin-B4 to stain perineuronal nets around PV+ neurons. In scrapie infected mice, cortical PV+ neurons were severely reduced while CB+ and CR+ neurons were well preserved. In CJD inoculated mice, loss of PV+ neurons was severe and occurred very early after inoculation. PrP-/- and tg20 mice showed normal appearance of PV, CB, CR, GAD+ neurons and their neuropil, and of isolectin-B4+ perineuronal nets. The early, severe and selective loss of cortical PV+ neurons in experimental scrapie and CJD suggest selective loss of PV+ GABAergic neurons as important event during disease development, possibly as one basis of excitatory symptoms in TSEs.
Biologic heterogeneity of angiomatous meningiomas.
Three angiomatous meningiomas, classified histologically as benign, were analyzed cytogenetically and examined for the expression of EGF/PDGF and their receptors by immunohistochemistry. An accumulation of p53 protein and the presence of mutations in exons 5-8 of the p53 gene in neoplastic cells were also determined. In one tumour, chromosome studies revealed near diploid karyotype with the loss of chromosome 22. Two other meningiomas revealed tetraploid karyotypes with the presence of telomeric associations and a wide spectrum of numerical, complex chromosome aberrations. Moderate EGF and EGFR immunoreactivity was found in three and one meningioma, respectively. All tumours exhibited diffuse PDGF and PDGFR-beta expression. No p53 gene mutations were found, but one tumour expressed strong and dispersed p53 immunopositivity. This findings reflect the biological heterogeneity of angiomatous meningiomas.
Desmoplastic cerebral astrocytoma of infancy: a case report.
We report a case of desmoplastic cerebral astrocytoma of infancy (DCAI), in a 7-month-old boy. DCAI belongs to a group of recently described central nervous system (CNS) tumors, which also includes desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA) and dysembryoplastic neuroepithelial tumor (DNT), all characterized by relatively favorable prognosis and occurring mostly in children and young adults. DCAI is a rare neoplasm arising in the cerebral hemispheres within the first two years of life, and histologically is characterized by dense fibrous desmoplasia. In our case, CT scan presents a massive partially cystic tumor of the left cerebral hemisphere with an enlargement of the ventricular system. Histologically, the tumor was composed of cells arranged in fascicles and whorls forming storiform pattern. Immunohistochemical stainings for glial fibrillary acidic protein proved glial histogenesis of this tumor, while no cells were unequivocally immunopositive for neuron specific enolase, neurofilament proteins and synaptophysin what excludes a diagnosis of DIG--a similar entity but containing also a neuronal elements. Our studies, comprising a complete clinical, radiological, histopathological and immunohistochemical data, correspond to a cases of DCAI published before and it is the first one described in Poland.