Biomedical subjects

R Kordek

Publications and source records attributed to R Kordek.

At least 55 records · Page 3Linked to original sources

PubMed1998

A comparative study of epidermal growth factor receptor (EGFR) and MDM2 gene amplification and protein immunoreactivity in human glioblastomas.

The gene of epidermal growth factor receptor (EGFR) is often altered in human astrocytomas and its amplification, rearrangement and overexpression occur almost exclusively in high grade tumours (glioblastomas). MDM2 gene is amplified in a small proportion of glioblastomas, and MDM2 immunoreactivity has also been found in this group. However, the relation between gene amplification and protein overexpression depends on several factors. Thus, the study on mutual relationship between these events needs to be clarified. In a series of 28 glioblastomas, we analysed MDM2 and EGFR gene amplification by differential PCR and protein overexpression was evaluated by immunohistochemistry. Thirteen cases (45%) presented immunopositivity for EGFR. A significant amplification of EGFR gene (the EGFR/SOD ratio above the control value +/- 3 SD) was observed in 9 tumours among which, one revealed no EGFR-immunopositivity. Three tumours displayed the ratio +/- 2-3 SD but these tumours also presented immunoreactivity for EGFR. Two other glioblastomas, with weak EGFR-expression, showed no gene amplification. The immunohistochemical staining for MDM2 revealed strong positivity only in one case, and this tumour also presented MDM2 gene amplification. On the contrary, another tumour which showed MDM2 gene amplification showed no MDM2 immunopositivity. In conclusion, our results demonstrate that there is no strict correlation between gene amplification at the DNA level and protein overexpression.

ErbB Receptors↗

PubMed1997

Molecular analysis of prion protein (PrP) and glial fibrillary acidic protein (GFAP) transcripts in experimental Creutzfeldt-Jakob disease in mice.

Prion protein (PrPsc) which accumulates in the brains affected with subacute spongiform encephalopathies (SSE) is altered isoform of normal, cellular isoform (PrPc), and PrP deposition is accompanied with spongiosis and astrogliosis. To find the amounts of PrP and GFAP transcripts during progression of experimental Creutzfeldt-Jakob disease we performed comparative RT-PCR on the terminally sick mice brains, 22 weeks following inoculation with Fujisaki strain of CJD agent, and on control brains. The intensity of bands for PrP-mRNA and control beta-actin were similar for infected and uninfected brains, while amounts of transcripts for GFAP increased as for cytokines released by glial cells-TNF-alpha and IL-1 alpha. This study supports thesis that PrPc to PrPsc conversion is post-translational process not related to PrP overproduction. Increased amounts of GFAP-mRNA during the course of the disease correlated with astrocytosis estimated by immunohistochemistry with anti-GFAP antibody.

Animals↗

PubMed1997

Ultrastructural study of subependymal giant cell astrocytoma: unusual paracrystalloid inclusions in tumour cells.

Subependymal giant cell astrocytoma (SEGA) is a tumour with a broad range of morphological, immunohistochemical and ultrastructural neoplastic cellular features. We report here the presence of this tumor in two 7-year-old-boys presented with a lateral intraventricular mass. Further clinical investigation confirmed the diagnosis of tuberous sclerosis. Ultrastructural and immunohistochemical investigation revealed that glial differentiation was more pronounced in these cases. Interestingly, tumour cells containing unusual paracrystalline inclusions, infrequently described in SEGA, were identified ultrastructurally. These inclusions are probably not related to other cellular organelles.

Brain Neoplasms↗

PubMed1997

TP53 mutations in malignant astrocytomas.

Astrocytomas are the most common tumors of the central nervous system (CNS). Their malignant counterparts, anaplastic astrocytoma and glioblastoma, are lethal neoplasms with poor clinical outcome and they frequently carry mutations of TP53 tumor suppressor gene. In order to determine the frequency and type of this molecular alteration in the Polish population, we analyzed the polymerase chain reaction products corresponding to the most conservative exons 5-8 for single-strand conformation polymorphism and confirmed the presence of mutations by direct DNA sequencing. We identified mutations in one of five (20%) anaplastic astrocytomas and in eight of 28 (29%) glioblastomas; the mutations were most frequently identified in the exon 8 (six glioblastomas). The frequency of TP53 mutations is thus similar to the corresponding data from other studies, and the type of mutations suggests the participation of endogenous etiological factor.

Adolescent↗

PubMed1997

Metaplastic meningioma with lipomatous changes.

We report here relatively rare lipomatous metaplastic changes, probably related to a prolonged clinical course, in not otherwise specified transitional meningioma. This lesion appears to have evolved over 30 years, with the initial diagnosis of multiple sclerosis. Histologically, it was composed of clusters and whorls of polygonal and spindle cells characteristic for transitional meningioma, with large areas of cells with lipid cytoplasmic accumulation, closely resembling mature adipocytes. The lipidization of other brain tumors and the histogenesis of these lesions in meningiomas on the background of meningeal embryogenesis are also discussed.

Adipocytes↗

PubMed1997

Programmed cell death (apoptosis) in Alzheimer's disease and Creutzfeldt-Jakob disease.

The aim of our study was the estimation of the apoptosis process using in situ-end labelling of DNA breaks method on paraffin sections in 5 human cases of Alzheimer's disease (AD), 6 of Creutzfeldt-Jakob disease (CJD) and in 25 mice infected experimentally with the Fujisaki strain of CJD, killed sequentially at one-week intervals. The numbers of apoptotic cells in CJD-infected mice in the later stages of the disease and in terminally ill mice were progressively higher that at the early stage of the disease. Further, we found a correlation between the intensity of apoptosis and major lesions hallmark of disease--the intensity of spongiform changes in the cerebral cortex but not in the accumulation of PrP in CJD infected mice. The number of A beta-amyloid plaques in AD was not related to apoptotic index. Our study showed that apoptosis is a very important event in these neurodegenerative diseases and may become a basic mechanism in loss of neurons.

Alzheimer Disease↗

PubMed1996

Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice.

The ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus is characterized by myelin sheath vacuolation that closely resembles that induced in murine spinal cord organotypic cultures by tumor necrosis factor alpha (TNF-alpha), a cytokine produced by astrocytes and macrophages. To clarify the role of TNF-alpha in experimental CJD, we investigated the expression of TNF-alpha in brain tissues from CJD virus-infected mice at weekly intervals after inoculation by reverse transcription-coupled PCR, Northern and Western blot analyses, and immunocytochemical staining. Neuropathological findings by electron microscopy, as well as expression of interleukin 1 alpha and glial fibrillary acidic protein, were concurrently monitored. As determined by reverse transcription-coupled PCR, the expression of TNF-alpha, interleukin 1 alpha, and glial fibrillary acidic protein was increased by approximately 200-fold in the brains of CJD virus-inoculated mice during the course of disease. By contrast, beta-actin expression remained unchanged. Progressively increased expression of TNF-alpha in CJD virus-infected brain tissues was verified by Northern and Western blot analyses, and astrocytes in areas with striking myelin sheath vacuolation were intensely stained with an antibody against murine TNF-alpha. The collective findings of TNF-alpha overexpression during the course of clinical disease suggest that TNF-alpha may mediate the myelin sheath vacuolation observed in experimental CJD.

Animals↗

PubMed1996

Proliferating tricholemmal cyst: a possible pitfall in cytological diagnosis.

We report a case of proliferating tricholemmal cyst, which made difficulties in the cytological analysis of the fine-needle biopsy aspirates. This rare dermatopathologic entity is a possible diagnostic pitfall due to its close cytological resemblance to squamous cell carcinoma-the abundance of material, with predominance of squamoid cells, which form concentric structures (so-called squamous eddies), that simulate keratin pearls of well-differentiated squamous cell carcinoma. However, careful and strict application of the cytological criteria prevents overdiagnosis; the small squamoid cells that predominate in the smears occur mainly in clusters and sheets, they do not show prominent atypia, and the squamous eddies may not undergo complete keratinization.

Adenoma↗

PubMed1996

Microwave treatment enhances the immunostaining of amyloid deposits in both the transmissible and non-transmissible brain amyloidoses.

The immunolocalization of amyloid deposits containing either protease-resistant prion protein (PrP) or amyloid beta protein (A beta) in the brains of patients with transmissible or non-transmissible cerebral amyloidoses has been greatly facilitated by the pretreatment of tissue sections with concentrated formic acid. We have investigated whether microwave processing of formalin-fixed tissue sections would obviate the need for formic acid pretreatment. Exposure of brain sections to microwaves, even for periods as brief as 1 sec, greatly enhanced the immunostaining of PrP and A beta amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. Microwaving for 1 min yielded staining intensities similar to that following pretreatment with concentrated formic acid for 10 min. Moreover, the combination of formic acid pretreatment and microwave processing resulted in an even more intense staining of amyloid deposits. Microwave processing, which is easy to perform and comparatively inexpensive, makes exposure to the potentially toxic fumes of formic acid unnecessary.

Alzheimer Disease↗

PubMed1996

Maltol (3-hydroxy-2-methyl-4-pyrone) toxicity in neuroblastoma cell lines and primary murine fetal hippocampal neuronal cultures.

Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocampal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 -(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apoptotic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized in situ in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans.

Animals↗

PubMed1996

Proliferating cell nuclear antigen (PCNA) and Ki-67 immunopositivity in human astrocytic tumours.

To compare the Ki-67 and Proliferating Cell Nuclear Antigen (PCNA), markers of cell proliferation, paraffin embedded surgical specimens from 56 human astrocytic tumours (8 pilocytic tumours, grade I; 9 low (II) grade and 9 anaplastic (grade III) astrocytomas and 30 glioblastomas, grade IV) were immunolabelled with the anti-PCNA (PC 10, DAKO) and anti-Ki-67 (DAKO) antibodies. For the latter immunostaining the microwave oven processing was performed. The Ki-67 and PCNA labelling indices (LIs) were statistically compared. For the majority of cases, PCNA LI was higher than that obtained with anti-Ki-67 antibody and the intensity of staining for PCNA was more variable. The statistically significant difference of the percentage of PCNA LIs was found only between low grade (I and II) and high grade (III and IV) tumours, while Ki-67 LIs discriminates each group of glial tumours; thus this latter marker is more sensitive and specific.

Astrocytoma↗

PubMed1996

Apoptosis in glial tumors as determined by in situ nonradioactive labeling of DNA breaks.

Tumor growth depends on cell division and cell death. To investigate the role of apoptosis in tumor cell death, we examined 83 cases of glial tumors using in situ nonradioactive tailing of DNA breaks. In addition, since p53 protein may participate in the regulation of apoptosis in glioblastoma, we compared the apoptosis ratio (AR) with the labeling index (LI) of p53 protein immunopositivity. The AR in glial tumor parenchyma ranged from 0 to 1.4%: mean AR +/- standard deviation was 0.4 +/- 0.4% (range, 0-1.4) for glioblastoma, 0.3 +/- 0.3% (range, 0.01-0.83) for anaplastic astrocytoma, 0.1 +/- 0.1% (range, 0-0.41) for low-grade astrocytoma, 0.006 +/- 0.008% (range, 0-0.02) for pilocytic astrocytoma, 0.2 +/- 0.2% (range, 0-0.62) for oligodendroglioma and 0.003 +/- 0.004% (range, 0-0.01) for ependymoma. ARs were significantly higher in higher-grade astrocytic tumors than in lower-grade tumors (Mann-Whitney U test: P = 0.0003), although wide variability in each group resulted in overlapping between the groups. p53 protein immunopositivity (more than 25% of nuclei) was found in 15 of 32 glioblastoma cases, while in the remaining 17 none or only a low percentage (up to 6%) of the nuclei were positive. In p53 protein-positive cases mean AR (0.51 +/- 0.47%) was not significantly higher than that in p53 protein-negative cases (0.22 +/- 0.23%; P = 0.1681).

Apoptosis↗

PubMed1996

Comparative evaluation of p53-protein expression and the PCNA and Ki-67 proliferating cell indices in human astrocytomas.

Mutations of the p53 gene are one of the most frequent genomic alterations of human tumours of astrocytic lineage. Because the physiological role of this gene is a suppression of cellular proliferation and growth, the overexpression of p53-protein may correlate with the expression of PCNA or Ki-67, established markers of cell proliferation. Paraffin-embedded surgical specimens from 60 human astrocytomas (9 pilocytic tumours, 12 WHO grade II, 9 anaplastic astrocytomas [WHO grade III] and 30 glioblastomas [WHO grade IV]) were stained with anti-PCNA (PC10), anti-p53(DO-7) and anti-Ki-67 antibodies (DAKO). Approximately 40% of all the cases were p53-protein immunopositive (53.3% glioblastomas, 33.3% anaplastic, 41.7% low grade astrocytomas but no pilocytic tumor). Statistical analysis did not reveal statistically significant correlation between p53-immunopositivity and PCNA or Ki-67 labeling indices. The Ki-67- and PCNA LI-s were statistically correlated, and the former better discriminated groups of different grades of malignancy.

Antigens, Neoplasm↗

PubMed1996

Phenotypic heterogeneity of nodular hidradenoma. Immunohistochemical analysis with emphasis on cytokeratin expression.

We studied the immunohistochemical phenotype in 13 cases of the nodular hidradenoma (NH), with special emphasis on the expression of different types of keratins (cytokeratins, 7, 10, 6/18, 8/18, and 10/17/18 and their distribution in normal sweat glands. Variable reactions with keratins, alpha-smooth muscle actin, and epithelial membrane antigen (EMA) were found, as these markers were present in different cellular components of the tumors. The most constant finding was almost complete absence of cytokeratins (all but keratin 10/17/18, which was positive in two of 13 cases) in clear cells, which yet were positive for EMA. The tumors expressed mostly cytokeratin 6/18, 7, 8/18, and 10/17/18, which were found in 11, 13, 11, and 12 cases, respectively. The cellular distribution and quantity of stained cells differed, as keratins 6/18, 8/18, and 7 produced the most abundant staining and were predominantly localized in small squamoid cells and the cells lining the tubular and cystic spaces. Cytokeratin 10/17/18 was expressed in smaller or larger clusters of squamoid cells and rarely in clear cells. Cytokeratins 10, 19, and 20 were found sporadically in single cells or small cellular clusters. alpha-Smooth muscle actin was expressed in four cases, whereas we did not find reactivity of S-100 protein. Comparing these results with the pattern of keratin distribution and antigenic reactivity in eccrine sweat glands, we conclude that NH presents cellular heterogeneity of its elements and differentiation toward different parts of the sweat gland.

Actins↗

PubMed1996

Carcinosarcoma of the skin. Case report and literature review.

A case of carcinosarcoma arising in the skin of the left arm of a 69-year-old woman is reported with a review of the literature. The tumor was composed of low-differentiated squamous cell carcinoma, which was intermingled with a pleomorphic sarcoma. The carcinomatous component had keratin and lacked vimentin, whereas the phenotype of the sarcomatous portion was the reverse. The former presented additionally focal expression of S-100 protein, which was lacking in other portions of the carcinoma. The phenotypic data, supplemented by p53 immunostaining, which was present in both components, suggest their common origin in this tumor.

Aged↗

PubMed1996

Expression of the latent membrane protein of Epstein-Barr virus in Hodgkin's disease. Age and subtype distribution in Polish patients.

We examined immunohistochemically 135 cases of HD (4, lymphocytic predominance (LP); 34, mixed cellularity (MC); 90, nodular sclerosis (NS) and 7, lymphocytic depletion (LD) for the presence of EBV latent membrane protein (LMP). Ten patients were younger than 14 years, 55 were young adults (15-34 years), 45 were 35-49-years old and 26 were older than 50 years. The average LMP-immunopositivity was 33% of all HD cases. The highest proportion of LMP-immunopositivity was found in the MC subtype (61.8%), followed by the NS (NS 1-25%, NS 2-26%) and the LD subtype (14%), but none in the LP subtype of HD. The differences between LMP-immunopositivity in the MC and NS subtypes were statistically significant in children and young adults (p < 0,01). The LMP-positivity was mainly associated with the MC subtype which occurred predominantly in children, while the lowest proportion of LMP-positive cases was found in the young adult group. This report supports a notion that there are regularities in age and subtype distribution of EBV in HD.

Adolescent↗

PubMed1996

The immunohistochemistry and ultrastructure of ganglioglioma with chromosomal alterations: a case report.

Ganglioglioma, together with its counterparts-ganglioneuroma and gangliocytoma are relatively uncommon neoplasms of the brain composed of neoplastic neurons (ganglion and ganglioid cells) and glial cells. We report here a case of ganglioglioma studied by electron microscopy. The case was further characterized by peculiar chromosomal alterations, 46,XX[6]/43,XX[1], der(1)t(1;5)(q21;q12), der(8;13)(q10;q10),-9,i(10)(q10). Routine light microscopy revealed mixed neuro-glial tumor composed of pilocytic astrocytes with abundant Rosenthal fibers and relatively numerous ganglion cells. The latter were immunoreactive with antibodies (Abs) against synaptophysin and neurofilament protein (NFP). Anti-NFP Abs also immunostained numerous distorted axons embedded in the tumor mass. Some of these showed bullous swellings and thus were analogous to dystrophic neurites or spheroids. Ganglion cells were characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers were seen. Dense-cored vesicles were pleomorphic and ranged in diameter from small synaptic vesicles to large lysosome-like neurosecretory granules. The former occasionally formed characteristic dumbbell shapes. Neoplastic astrocytes were identical to those of other glial tumors of astrocytic lineage; numerous Rosenthal fibers were frequently seen.

Brain Neoplasms↗

PubMed1996

Diagnostic significance of the myoepithelial cells in the benign and malignant sweat gland tumors.

We studied the presence of myoepithelial cells (MCs) in the benign and malignant sweat gland adenomas by immunostaining with antibody to alpha-smooth muscle actin. We found peripheral arrangement of MCs in the neoplastic nests in cutaneous cylindromas (9), spiradenomas (13), syringoadenomas (7), and one case of adenoid cystic carcinoma. Dispersed MCs were identified in some cases of nodular hidradenoma (7/13) and malignant portion of spiradenocarcinoma (2/3). The remnants of the peripheral arrangement of MCs were retained in the benign part in cylindrocarcinoma and every case of spiradenocarcinoma, likewise in composed malignant adnexoma (malignisation within cylindroma/spiradenoma). We could not find MCs in papillary eccrine adenoma (2), poromas (7) and porocarcinomas (3), syringomas (6), chondroid syringomas (3), malignant nodular hidradenoma (1) and malignant portion of syringoadenoma (1). In one of three cases of eccrine hidradenocarcinoma focal myoepithelial differentiation could be identified at the periphery of the epithelial nests. These results confirm heterogeneity of the differentiation in sweat gland tumors, emphasizing the validity of division of those tumors into those with the differentiation towards secretory and ductal portion of the gland. The former group demonstrates the variability of arrangement of myoepithelial cells depending on the degree of dedifferentiation of the developing carcinoma. These cells may be replaced by outgrowing tumor, but may also accompany the neoplastic growth. Less significant is the presence of the MCs in the adenomas with ductal differentiation, which either in benign and malignant tumors may be lacking. The variability of MCs occurrence in cutaneous adenomas and carcinomas precludes its significance as a solitary factor in the differentiation between benign and malignant proliferations.

Diagnosis, Differential↗